B Y T

K THUT BO CH
-

V SINH DIC HC
CC DNG THUC
SCH DNG O TO DC s I HC
> a

Tp 1
 KY THUT BAO CHE VA
SINH DC HC CC DNG THUC
(Sch dng o tao dc s i hoc)

M S: 20 z 04

TP I

NH XUT BN Y HC

H NI - 2006
CH BIN:

PGS.TS. V Xun Minh - PGS.TS. Phm Ngc Bng

CC TC G I:

PGS.TS. Phm Ngc Bng

TS. Hong c Chc
TS. Nguyn ng Ha
PGS.TS. V Xun Minh

THAM G IA T CHC BN TH O :

TS. Nguyn Mnh Pha

ThS. Ph Vn Thm

Bn quyn Thuc B Y t (V Khoa hc v o to)

 LI NI U

Thc hin Ngh nh 43/2000 /N-CP ngy 30/8/2000 ca chnh ph quy nh

chi tit v hng dn trin khai Lut gio dc, B Gio dc & o to v B Y t
ph duyt, ban hnh chng trnh khung cho o to Dc s i hc. B Y t t chc
thm nh sch v ti liu dy - hc cc mn c s v chuyn mn theo chng trnh
mi nhm tng bc xy dng b sch chun trong cng tc o to Dc s i hc
ca Ngnh Y t.
Cng vi s pht trin ca cc ngnh khoa hc k thut khc, trong nhng nm
qua, k thut bo ch c nhng bc tin ng k. T thp k 70 ca th k 20,
sinh dc hc bo ch ra i nh du bc chuyn v cht t bo ch quy c
sang bo ch hin i. Nhiu k thut bo ch v cc dng thuc mi ra i, p
ng nhu cu dng thuc ngy cng cao ca ngi bnh. gip sinh vin cp nht
c kin thc, B mn Bo ch Trng i hc Dc H Ni bin son b gio
trnh "K thut bo ch v sinh dc hc cc dng thuc", bc u b sung nhng
hiu bit v sinh dc hc bo ch, mt s k thut v dng thuc mi.
B sch bao gm 13 chng chia lm 2 tp, c sp xp theo h phn tn ca
cc dng thuc. Mi chng c trnh by ni bt cc ni dung: mc tiu, ni dung
chuyn mn; m bo 4 yu cu c bn v kin thc, tnh chnh xc v khoa hc, cp
nht tin b khoa hc k thut vn dng thc tin. Phn cu hi lng gi i km tng
chng c bin son thnh mt tp ring. Mt s kin thc chuyn su s c trnh
by trong cc chuyn sau i hc. Ngoi vic dng lm ti liu hc tp cho sinh
vin, b sch cng rt b ch cho cc bn ng nghip trong v ngoi ngnh.
B sch c Hi ng chuyn mn thm nh sch gio khoa v ti liu
dy - hc chuyn ngnh Dc ca B Y t thm nh v c B Y t ban hnh lm ti
liu dy - hc chnh thc ca Ngnh Y t trong giai on hin nay.
V Khoa hc v o to xin chn thnh cm n cc ging vin B mn Bo ch-
Trng i hc c H Ni b nhiu cng sc bin son b sch ny.
V l ln u tin xut bn nn chc chn b sch khng trnh khi thiu st.
V Khoa hc v o to mong nhn c kin ng gp ca cc bn ng nghip v
sinh vin b sch ngy cng c cht lng tt hn.

V KHOA HC V O TO
B Y T

3
 MC
LC

Li ni d u 3

CHNG 1. I CNG V BO CH V SINH D c HC 11

PG S.TS. V X un M inh
I. i cng v bo c h 11
1 . Khi nim v bo ch 11
2. Vi nt v lch s v pht trin 12
3. Mt s khi nim hay dng trong bo ch 14
4. V tr ca mn bo ch 18

II. i cng v sin h dc hc ^

1 . Mt s" khi nim hay dng 19
2 . Cch nh gi sinh kh dng v ngha trong bo ch v hng dn 23
s dng thuc
3. Cc yu t' thuc v dc cht nh hng n sinh kh dng 32
4. Cc yu t thuc v ngi dng thuc nh hng n sinh kh dng 41

CHNG 2. DUNG DCH THUC 45

PG S.TS. Phm Ngc B ng
I. i cng v d u n g d ch th u c 45
1 . nh ngha v c im 45
2. Phn loi dung dch 46
3. u nhc im ca dung dch thuc 46
4. T hnh phn ca dung dch thuc 47
5. Phn loi cht tan, dung mi theo phn cc v kh nng ho tan 47
6 . tan ca cht tan v nng dung dch 48

II. D ung m i chnh dng iu c h dung dch th u c 49

1 . Nc - k th u t iu ch nc ct v nc kh khong 49
2 . Cc dung mi phn cc th n nc 57
3. Cc dung mi khng phn cc th n du 58

5
 III. K th u t ch u n g iu c h d u n g d ch th u c 58
1 . Cn, ong dc cht v dung mi 58
2. Ho tan v cc yu t' nh hng 58
3. Lc dung dch 67
4. Hon chnh, ng gi v kim nghim th n h phm 72
5 . Pha ch dung dch thuc theo n 72

IV. Mt s d u ng d ch th u c u n g v d ng n goi 73
1 . Dung dch thuc nc 74
2. Siro thuc 77
3. Thuc nc chanh 86
4. Nc thm 88
5. Potio 91
6 . Elixir 94
7. Dung dch cn (ethanol) thuc 96
8 . Dung dch glycerin 97
9. Dung dch du 99
10. Dung dch cao phn t v dung dch keo 101

CHNG 3. THUC TIM - THUC NH MAT 103

TS. Nguyn ng Ha
THUC TIM 103

I. i cng v th u c tim
1. nh ngha 103
2 . Cc ng tim thuc 104
3. Phn loi thuc tim 105
4. Nhng u im v hn ch ca dng thuc tim 105

II. T hnh phn th u c tim 107

1.Dccht 107
2. Dung mi hay cht dn 108
3. Cc thnh phn khc trong cng thc thuc tim 112
4. Bao b ng thuc tim 129

6
III. K th u t pha c h th u c tim 139
1 . C s, thit b dng pha ch - sn xut thuc tim 139
2 . Quy trnh pha ch - sn xut 147

IV. Yu cu ch t lng i vi th u c tim 153

1 . Ch tiu cm quan 153
2. nh tnh, nh lng 155
3. Th tch hoc khi lng 155
4. pH 155
5. V khun 155
6 . C ht gy st (pyrogen) 155
7. Ni c t" vi khun 157

V. S in h kh d ng c a th u c tim 157
1 . nh hng ca cc yu t" dc hc n sinh kh dng ca thuc tim 157
2 . nh hng ca yu t sinh hc n sinh kh dng ca thuc tim 161
VI. Mt s c n g th c th u c tim 163

THUC TIM TRUYN 166

I. i cng 166
1 . nh ngha 166
2 . c tnh ca thuc tim truyn 166
3. p dng lm sng 167

II. Mt s c n g th c th u c tim tru y n 168

1 . Cc dung dch tim truyn cung cp nc 168
2 . Cc dung dch tim truyn cung cp cht in gii 169
3. Cc dung dch tim truyn lp li cn bng acid-kim 172
4. Cc dung dch tim truyn cung cp cht dinh dng 174
5. Cc dung dch b sung th tch m u 176
6 . Cc dung dch tim truyn li niu thm th u 177
7. Cc dung dch chng ng v bo qun m u 177
8 . Mt s dung dch khc 179

7
 THUC NH MT 180
I. i cng 180
1 . Cc ng dng thuc trong iu tr bnh v m t 180
2 . Cc dng bo ch dng ti ch trong iu tr bnh m t 181
3. Mt s" c im sinh l ca m t lin quan n s hp th u dc cht 182
t thuc nh m t

II. Thnh phn th u c nh m t 184

1.Dccht 185
2. Dung mi 186
3. Cc cht thm vo cng thc thuc nh m t 186
4. Bao b ng thuc nh m t 194

III. K th u t pha c h - sn xu t th u c nh m t 194

1 . Nh xng v thit b 194
2 . Quy trnh pha ch 195

IV. Kim tra ch t lng th u c nh m t 197

1 . V khun 197
2. Cm quan 197
3. Cc ch tiu khc 198
V. Sinh kh dng v cc bin php tc n g kh i xy d ng cn g th c 198
thu c nh m t

1. Ko di thi gian lu thuc vng trc gic mc 199

2. Hn ch gy kch ng m t 200
3. Lm tng tnh thm ca gic mc i vi dc cht 200
VI. Mt s cng thc th u c nh m t 201

CHNG 4. CC DNG THUC IU CH

BNG PHNG PHP CHIT XUT 204
PG S.TS. Phm Ngc Bng
I. i cng 204
1. nh ngha 204
2 . Dc liu v dung mi iu ch dch chit 205
3. Bn cht ca qu trnh chit xut 208

8
 4 . Cc phng php chit xut thng dng trong k th u t bo ch 211
5 . Cc yu t' nh hng n hiu su t v cht lng dch chit 219
6 . Cc giai on sau khi chit xut 222
II. Cc dn g th u c iu c h bng phng php c h i t xu t 222
1 . Cn thuc 222
2. Ru thuic 228
3. Cao thuc 229
4. Cao ng vt 235

CHNG 5. NH TNG V H N DCH THUC 237

TS. Hong c Chc
NH TNG THUC 237
I. i cng 237
1 . nh ngha 237
2. Thnh phn ca nh tng thuc 238
3. Cc kiu nh tng 238
4. Phn loi nh tng thuc 239
5. u nhc im ca dng thuc nh tng 241

II. Cc ch t nh ho th ng d n g tro n g bo c h th u c nh tng

1 . Yu cu i vi cht nh ho 242
2 . Cc cht nh ho thng dng 243

III. Cc y u t nh hng n s h n h th n h , n n h v sin h 254

kh d n g c a nh t ng th u c
1 . Anh hng ca sc cng b m t phn cch pha 254
2. Anh hng ca cht nh ha 255
3. nh hng ca lp in tch cng du xung quanh cc tiu phn pha 256
phn tn
4. nh hng ca nht mi trng phn tn 257
5. Anh hng ca t trng hai pha 257
6 . Anh hng ca nng pha phn tn 258
7. Anh hng ca phng php phi hp cht nh ha 259

9
 8 . nh hng ca phng php phi hp cc pha 260

9. nh hng ca cng v thi gian tc dng lc gy phn tn

10 . nh hng ca nhit v pH mi trng phn tn 261
IV. Cc phng php nh ho thng dng iu c h nh tng thu c 261
1. Phng php kt t 262
2 . Cc phng php s dng lc gy phn tn 262

V. K th u t iu c h nh tng th u c u n g 267
1 . K th u t iu ch nh tng thin nhin 268
2. K th u t iu ch potio nh tng 269
3. K th u t iu ch nh tng du thuc 270

VI. Kim sot cht lng nh tng thuc, ng gi v bo qun 271

1 . Xc nh kiu nh tng 271
2 . Xc nh cc thng s" ca nh tng 271
3. ng gi v bo qun nh tng thuc 271

HN DCH THUC 273

I. i cng 273
1 . nh ngha, th n h phn v c im ca hn dch thuc 273
2 . Phn loi 275
3. u nhc im ca dng thuc hn dch 275
4. Yu cu cht lng ca thuc hn dch 276
II. Cht gy thm - n n h h n d ch th u c 277
III. Cc yu t nh h ng n s h n h th n h , n n h v sin h 277
kh dng ca th u c h n dch
IV. K t h u t i u c h h n d c h th u c 280
1 . Cc trng hp iu ch thuc th n h dng hn dch 280
2 . K th u t iu ch hn dch thuc 280
3. Bt v cm pha hn dch 285
V. Kim tra ch t lng hn d ch th u c 286
T i li u th a m k h o 287

10
 Chng 1

I CNG V BO CH V SINH DC HC

MC TIU
1. Trnh by c cc khi nim hay dng trong bo ch dng thuc, ch
phm , bit dc.
2. Trnh by c cc khi nim hay dng trong sinh dc hc: sinh dc
hc, sinh kh dng, tng ng.
3. Nu c cch nh gi v ngha ca sinh kh dng.
4. Nu c cc yu t thuc v dc cht nh hng n sinh kh dng.

NI DUNG

I. I CNG V BO CH

1. Khi nim v bo ch

T thi nguyn thu, con ngi bit dng cy c v khong vt quanh

m nh cha bnh. T ch ban u dng cc nguyn liu lm thuic tr n g th i
t nhin, dn dn ngi ta bit ch bin, bo ch chng th n h cc dng thuc
n gin tin dng v d tr dng hng ngy.
Cng vi s p h t trin ca cc ngnh khoa hc khc, vic bo ch thuc
ngy cng c nghin cu hon thin v p h t trin th n h mt trong nhng mn
hc chnh ca N gnh Dc.
Bo ch hc l mn hc nghin cu c s l lun v k th u t thc hnh v
pha ch, sn xu t cc dng thuc; v tiu chun cht lng, cch ng gi v bo
qun cc dng thuc nhm p h t huy cao nht hiu lc iu tr ca thuc, m
bo an ton, thun tin cho ngi dng v p ng c hiu qu kin h t.
Trn thc t, dc cht t khi c dng trc tip cho ngi bnh, bo ch l qu
trnh chuyn dc cht thnh dng thuc ngi bnh d dng tip nhn thuc.
Mc tiu ca mn hc bo ch l: sau khi hc, ngi hcc kh nng:
- T rnh by c th n h phn chnh ca dng thuc.
- Nu c nguyn tc bo ch v cu to ca dng thuc.
- P ha ch c cc dng thuc thng thng.
- Nu c tiu chun cht lng ca dng thuc v cch nh gi.
- nh gi c n nh ca dng thuc

11
 - Gii thch c cch ng gi, bo qun dng thuc.
- Hng dn ng cch dng.
- Gip thy thuc v ngi bnh la chn c dng thuc tt.
T trc, trong bo ch, nhim v ca ngi dc s ch yu l pha ch theo
n thy thuic v cp ph t cho ngi bnh, do h thng i su vo vic rn
luyn cc th th u t pha ch v k nng thao tc chuyn mn. H in nay trong
cng nghip bo ch, vic sn xut c t ng ho mc cao, vai tr ca
ngi dc s trong sn xut ch yu l:
- T hit k dng thuc cho ph hp vi i tng iu tr,
- Xy dng cng thc bo ch thch hp n h t cho dng thuc.
- T rin khai v kim sot qu trn h sn xut theo quan im sn xu t tt
m bo cht lng ca dng thuc, trong c b it lu n ch t lng
sinh dc hc.

2. Vi nt v lch s pht trin

Lch s pht trin ca bo ch hc gn lin vi s pht trin ca Ngnh Dc.

Trn th gii, trong cc ti liu c cch y khong 3000 nm c nhng
sch ghi chp v k th u t bo ch cc dng thuc. Th d nh trong kinh "Vedas"
ca n , trong "Bn tho cng mc" ca T rung Quc m t cc dng thuc
bt, vin trn, cao thuc...
Vo th k th V trc cng nguyn, cc nh tri t hc kim th y thuc ni
ting ca La M - Hy Lp nh Platon, Socrat, Aristot... i su nghin cu cc
phng php cha bnh v bo ch thuc. Nm 400 trc cng nguyn, Hypocrat
a khoa hc vo thc hnh y dc hc da trn c s thc nghim v bin
son nhiu sch y dc hc c gi tr.
Tuy nhin, bo ch hc ch c coi l b t u vi s cng hin ca Claudius
Galenus (2 1 0 -1 3 1 trc cng nguyn). ng l ngi gc T rung ng, sang La M
bo ch thuc cho Hong gia. ng li 500 tc phm v y hc, trong c tp
sch dnh cho vic phn loi thuc c ghi chi tit v cch pha ch m t s" dng
thuc. T ng c coi l ngi sng lp ra mn bo ch hc v ngi ta ly
tn ng t tn cho mn hc (Pharm acie Galenique) [1].
T th k th XIX, do s ph t tri n ca cc ngnh khoa hc lin quan nh
vt l, ho hc, sinh hc... N gnh Dc ni chung v k th u t bo ch ni ring
c s p h t trin m nh m. Mt lot cc dng thuc mi ra i: thuc tim , thuc
vin nn, nang mm,... L thuyt v bo ch c xy dng trn c s khoa hc
do vn dng th n h tu ca cc mn khoa hc c bn v c s. Ngnh cng nghip
dc phm ra i.
Sau i chin th gii ln th 2, do c s tc ng ca cuc cch m ng khoa
hc k th u t trn phm vi ton th gii, ngnh bo ch quy c t c nh
cao. Hng lot bit dc c sn xut quy m cng nghip ra i vi m y mc
hin i c nng su t cao (my dp vin quay trn, my ng nang, m y ng

12
hn ng tim t ng...) c hnh thc trn h by p, hp dn th ay th dn cc
ch phm pha ch theo n hoc bo ch quy m nh.
Tuy nhin cng b t u t nhng nm 60, ngi ta nhn th y rn g mt
dng thuc c hnh thc p, cha chc c tc dng tt. N hng nghin cu bt
u t M cho thy mt lot bit dc tuy cng mt dng thuc, c hm lng
dc cht nh nhau (tng ng v bo ch), nhng p ng sinh hc li khng
ging nhau (khng tng ng v sinh hc). i su nghin cu nguyn n hn ca
nhng hin tng khng tng ng ny hnh th n h nn mn sinh dc hc
(biopharmacy). Sinh dc hc bo ch nhn m nh vai tr ca t dc, ca k
th u t bo ch, ca bai b i vi sinh kh dng (bioavailability) ca thuc. T
thc y s pht trin ca cng nghip t dc v cng nghip bao b. H ng lot t
dc mi v bao b mi ra i nng cao cht lng ca cc ch phm bo ch.
Vic ra i ca sinh dc hc (SDH) nh du mt giai on chuyn tip
t bo ch quy c (conventional pharm aceutics) sang bo ch hin i (modern
pharm aceutics). Trong bo ch hin i, cht lng ca dng thuic khng ch
c nh gi v m t l - ho hc m cn c nh gi v phng din gii
phng v hp th u dc cht (sinh kh dng). N hiu dng thuc c sinh kh dng
(SKD) ci tin (modied biovailability) ra i: Thuc tc dng ko di
(sustained release), thuc gii phng c kim sot (controlled release), thuc gii
phng theo chng trn h (programmed release),... y l nhng h iu tr
(therapeutic systems) c kh nng duy tr nng thuic trong m u trong vng
iu tr mt khong thi gian kh di nhm nng cao SKD ca thuc.
Trong nhng nm gn y, bo ch hin i ang c xu hng i vo th
gii siu nh, ch ra cc nanocapsule, nanosphere, liposome, niosome... c kch
thc c nanom et... trong nhng c gng nhm a thuc ti ch.
Hin nay, bn cnh cc bit dc c sn xut hng lot quy m cng
nghip, hnh thc pha ch theo n c duy tr b p cho s thiu h t ca
sn x ut ln v gip cho vic iu chnh thuc ph hp vi tng c th ngi
bnh trong dc lm sng.
nc ta, t lu nn y dc hc c truyn ra i v pht trin. Nhiu dng
thuc cao, n, hon, tn c dng kh ph bin trong nhn dn.
Cc danh y ln nh Tu Tnh (th k XIV), H i Thng Ln ng (th k
XVII) c nhiu pho sch ln m t cc v thuc v cc phng php ch bin,
bo ch cc dng thuc c truyn.
Di thi Php thuc, Trng i hc Y-Dc ng Dng c th n h lp
(1902), trong c B mn Bo ch (1935). N hiu bit dc c a vo nc ta,
mt s' ca hng pha ch theo n ra i cc th n h ph" ln pha ch cc dang
thuc thng thng: thuc bt, thuc nc, thuc m...
T nhng ngy u ca cuc k h n g chin chng P hp, "Vin kho cu v
ch to dc phm " thuc Cc Q un Y c th n h lp nghin cu v sn
x u t thuc bng nguyn liu trong nc. N gnh bo ch c nh ng ng gp
ng k trong vic pha ch thuc cung cp cho b i v n h n dn.

13
 Sau ho bnh lp li, nhiu x nghip dc phm (XNDP) tru n g ng c
th n h lp. Cc khoa dc bnh vin cng pha ch nhiu loi thuc, n h t l cc
loi dch truyn.
Trong nhng nm khng chin chng M cu nc, hng lot cc x nghip
dc phm a phng ra i, to th n h mt m ng li pha ch, sn x u t thuc
rng khp, m bo c vic t tc nhu cu thuc phc v cho chin u v bo
v sc khe nhn dn.
Sau khi thng n h t t nc, n h t l t ngy c chnh sch i mi, nhiu
XNDP tch cc i mi tran g th it b v quy trn h cng ngh. N hiu th i t b v
k th u t mi c a vo nc ta: my dp vin nng su t cao, m y ng nang,
my p v, my bao m ng mng t ng, m y to h t tn g si, m y ng h n ng
tim t ng, ... Do vy, dng bo ch thc s c i mi v h n h thc.
Tuy vy, ngnh bo ch nc ta vn ch l bo ch quy c. Thuc ch mi
c nh gi v m t c, l - ho hc ch cha c ch tiu v SKD v tng ng
sinh hc. Cc t dc mi cha c s dng mt cch rng ri, cn k h nhiu
XNDP cha t tiu chun thc h n h tt sn xu t (GMP). Vic pha ch theo n
hu nh b b qun.

3. Mt s khi nim hay dng trong bo ch

3.1. Dng thuc (dng bo ch)

Dng thuc l sn phm cu cng ca qu trn h bo ch, trong dc cht

c pha ch v trn h by di dng thch hp m bo an ton hiu qu,
th u n tin cho ngi dng, d bo qun v gi th n h hp l.
Th d: cloramphenicol l dc cht c v ng kh ung. Ngi ta bo ch
thnh dng vin nn, nang cng hoc hn dch hn ch v ng, lm cho ngi
bnh d tip nhn thuc, nng cao hiu qu iu tr ca thuc.
Trn thc t, dc cht t khi c dng mt m nh m thng cho thm cc
cht ph tr tin bo ch th n h dng thuc. Do , th n h phn ca dng thuc
ngoi dc cht cn c: t dc, v t liu bao gi (vi s tc ng trc tip ca k
th u t bo ch) theo s di y:

m bo pht huy ti a tc dng iu tr ca dc cht khi dng, khi

thiet k dng thuc, ngoi cc th n h phn nu trn, cn phi xem xt cc yu t"
anh hng n qu trn h gii phng v hp th u ca dc cht trong c th ngi
bnh nh ng dng, la tui, tn h trn g bnh...

14
 - Dc cht: l th n h phn chnh ca dng thuc, to ra tc dng dc l
iu tr, phng hay chn on bnh.
Khi th it k dng thuc phi xem xt k tn h cht l ho ca dc cht
la chn t dc, k th u t bo ch v bao b cho ph hp nhm p ng ti a yu
cu ca dng thuc.
Th d: vitam in c l dc cht t n nh v m t ho hc. Khi bo ch phi
la chn t dc, k th u t bo ch v bao b thch hp ko di tui th ca
vitam in trong qu trn h bo ch v bo qun dng thuc (vin nn, thuc tim...)
Khi a vo dng thuc, trong qu trn h bo ch, tc dng dc l ca dc
cht c th b thay i.
Th d: tetracyclin hydroclorid nu dp vin vi t dc dicalci phosphat,
khi ung, tc dng ca tetracyclin s b gim do to phc t tan vi dicalci
phosphat lm gim hp thu.
- T dc: nh trn ni, bo ch l qa trn h chuyn dc cht th n h
dng thuc, trong khi u l vic la chn t dc xy dng cng thc bo
ch (brmulation).
Trc kia ngi ta thng quan nim t dc l cht tr v ho hc v dc
l, nhng trn thc t t c cc cht tr nh vy. Trong qu trn h bo ch v bo
qun dng thuc, t dc nh hng trc tip n n nh ca dc cht v
ca dng thuic. Khi dng, t dc nh hng n kh nng gii phng v hp
thu ca dc cht trong c th, tc l nh hng n p ng lm sng ca thuic.
Do , t dc phi c la chn mt cch th n trng theo tng dng thuc v
tng cng thc bo ch c th.
- Bao b: dng ng, trn h by v bo qun dng thuc. Bao b gi cng
l mt th n h phn ca dng thuc v n tip xc trc tip vi dc cht v nh
hng n cht lng dng thuc. c bit l trong qu trn h bo qun, di tc
ng ca cc iu kin ngoi mi nh nhit , m, nh sng, bc x, c th
dn n nhng tng tc gia thuc v v ng lm bin cht dc cht, lm
gim tui th ca dng thuc.
Th d: v ng thu tin h kim c th lm k t t a dc ch t l mui
ancaloid trong thuc tim . Mt s tp cht trong l nh a ng dung dch thuc
nh m t c th lm tn g qu trn h phn hu dc ch t c trong dung dch.
Theo quan im ca bo ch hc hin i, th i t k dng thuc l k h u quan
trng quyt nh cht lng ca dng thuic. Khi th i t k dng thuc, phi xem
xt mi tng quan gia cc th n h phn trong dng thuc di s tc ng trc
tip ca k th u t bo ch nhm tm ra phng n ti u cho tng sn phm.
Trong bo ch hc hin i, k th u t bo ch lun lun c i mi v hon thin
nhm p h t huy ti a tc dng ca dc cht trong c th v to ra nhng dng
thuc mi c hiu qu iu tr cao.

15
 Dng thuc c th c phn loi theo nhiu cch.
- Theo th cht:
+ Cc dng thuc lng: dung dch thuc, siro thuc, potio, cao lng, hn
dch thuc,...
+ Cc dng thuc mm: cao mm, thuc m...
+ Cc dng thuc rn: bt thuc, vin nn, nang cng, cm thuc...
- Theo ng dng-, l cch phn loi hay gp hin nay trong SDH bo ch,
gn dng thuc vi ng dng thuc.
+ Dng thuc dng theo ng tiu ho: bao gm cc loi thuc ung,
ngm hay nhai (trong dc cht c hp th u hoc gy tc dng ti ch ch
yu rut non), thuc t v thuic th t (gy tc dng t i ch hoc c hp thu
ch yu i trng).
Thuc dng qua ng tiu ho thng c vn v hp th u do b tc ng
ca nhiu yu t" nh pH dch tiu ho, men, thc n, chuyn ho qua gan ln
u, thi gian vn chuyn ca thuc...
+ Dng thuc dng theo ng h hp: bao gm cc dng thuc xng,
ht, phun m, nh mi... Cc dng thuc ny c th gy tc dng ti ch trn
nim mc ng h hp hay tc dng ton thn.
+ Dng thuc dng theo ng da: bao gm cc dng thuc m, thuc
bt, thuc nc, cao dn, h iu tr qua ng da, thuic phun m... P h n ln
thuc dng trn da l gy tc dng ti ch (cha m n nga, bo v da...),
nhng cng c nhng trng hp dc cht c hp th u qua da gy tc dng
ton th n (chng au th t ngc, say tu xe...)
+ Thuc tim: c nhiu loi thuc tim khc nhau: tim di da, tim
bp, tim hoc truyn nh git tn h mch.
ng dng nh hng nhiu n tc dng ca thuc. Mt dc ch t a
vo c th theo cc con ng khc nhau c th gy tc dng dc l khc nhau.
Th d: m agnesi sulfat nu ung th c tc dng li m t; n h u n ty; cn nu
tim th c tc dng chng ph n.
- Theo cu trc h ph n tn:
Cc dng thuc, thc cht l nhng h phn t n khc nhau, tu theo mc
phn tn ca dc cht trong h, ngi ta c th xp cc dng bo ch th n h cc
nhm sau:
+ Cc dng thuc thuc h phn t n ng th: bao gm cc dng thuc c
dc cht phn tn di dng phn t hoc ion (dung dch thuc ung, thuc
tim,...). H micel (dung dch keo, dch chit dc liu...) tr n thc t l h phn
tn siu vi d th (c ng knh tiu phn phn t n t 1 - lOOnm) nhng trong
bo ch thng c iu ch bng phng php ho ta n v lc qua v t liu lc
thng thng nn c xp vo h phn tn ng th.

16
 + Cc dng thuc thuc h phn t n d th: dng thuc bao gm 2 pha
khng ng tan: pha phn tn v mi trng phn t n (nh tng v hn dich
thuc), trong kch thc tiu phn phn t n thay i t hng trm nanom et
n hng trm micromet. y l nhng h phn t n km n nh v m t nhit
ng hc.
+ Cc dng thuc thuc h phn t n c hc: l h phn tn gia cc tiu
phn rn, c kch thc t hng chc n hng trm ngn micromet, bao gm cc
dng thuc rn nh thuc bt, nang cng, thuc vin...
S phn loi trn y ch l tng i. Trn thc t, trong mt s" ch phm
bo ch c th gm nhiu h phn tn.
- Theo ngun gc cng thc:
+ Thuc pha ch theo cng thc dc dng: l nhng ch phm bo ch
m th n h phn, cch pha ch, tiu chun cht lng v cch nh gi,... u
c quy nh trong cc ti liu chnh thng ca ngnh (dc in, dc th, cng
thc quc gia,...). Khi pha ch, kim nghim cht lng phi theo ng nhng quy
nh c thng nht. Th d:
Dung dch iod 1% (DVN II)
Iod lg |
Kali iodid 2g
Nc ct v. lOOml
C h phm phi p ng cc yu cu v tnh cht, nh tn h v nh lng
nh quy nh.
Thuc pha ch theo cng thc dc dng c th pha quy m nh trong
cc ca h n g ph a ch theo n hoc c sn x u t ln quy m x nghip.
+ Thuc pha ch theo n: l nhng ch phm pha ch theo n ca thy
thuc.
Ni dung mt n thuc thng bao gm: m nh lnh pha ch (Rp.)> cng
thc pha ch (th n h phn, s lng), dng bo ch cn phi pha s' lng
cn pha, hng dn cch dng (D.S). Th d:
Rp. A spirin 0,5g
B cacao v. l,5g
M.f. supp. D .t.d No 6
D.S: t mt vin khi au
Trc khi pha ch, ngi pha phi kim tra li n thuc, xem xt li liu
dng, cch phi hp thuc trong (ch tng k), dng bo ch,... Nu p h t
hin c nhng iu cha hp l th trao i li vi ngi k n. Khi cp p h t cho
ngi bnh phi hng dn r cch dng, cch bo qun.
P ha ch theo n thng c tin hnh quy m nh, ti cc khoa dc
bnh vin hoc cc quy pha n ca hiu thuc. Pha ch theo n r t ph hp
vi tnh trn g bnh ca tng c th ngi bnh, do hiu qu iu tr cao, cn
c duy tr v p h t trin.

17
3.2. C h phm

L sn phm bo ch ni chung ca mt hoc nhiu dc cht. Th d:

V itam in c c ch phm vin nn, thuc tim. Trong vin nn li c nhiu
ch phm c hm lng v cch bo ch khc nhau (vin trn , vin bao, vin S1
bt...).
Trong nhiu trng hp, ch phm bo ch ch l mt sn phm tru n g gian
bo ch cc dng thuc khc (cao thuc, vi nang, pellet...).

3.3. B i t dc
L ch phm bo ch lu hnh trn th trng di m t tn thng m i do
nh sn xut t ra v gi bn quyn nhn hiu hng ho.
T mt dc cht tn gc thng c nhiu bit dc khc n h au do cc nh
sn xut khc nhau t ra. Th d: t paracetam ol hin nay tr n th trng c ti
hng trm bit dc nh: Pamol, Panadol...

4. V tr ca mn bo ch

Bo ch l mn hc k th u t, ng dng th n h tu ca nhiu mn hc c bn,

c s v nghip v ca ngnh. Th d:
- Ton ti u c ng dng th i t k cng thc v dng bo ch.
- Vt l, ho hc c vn dng nh gi tiu chun nguyn liu v ch
phm bo ch, nghin cu n nh xc nh tui th ca thuc, n h gi
SKD ca thuic, la chn iu kin bao gi, bo qun...
- Dc liu, dc hc c truyn c vn dng trong vic ch bin, n h gi
cht lng cc ch phm bo ch i t nguyn liu l dc liu.
- Sinh l - gii phu, dc ng hc c vn dng trong nghin cu th it
k dng thuc v cc giai on SDH ca dng thuc (la chn ng dng v vn
gii phng, ho tan v hp th u dc cht t dng bo ch).
- Dc liu, dc lm sng ng dng phi hp dc cht trong dng bo
ch, hng dn s dng ch phm bo ch...
- Cc quy ch, ch v hot ng chuyn mn ngh nghip c vn dng
trong thit k, xin php sn xut v lu hnh ch phm bo ch.
Tm li bo ch hc l mn hc tng hp, vn dng kin thc ca nhiu lnh
vc khoa hc. Trong chng trn h o to dc s i hc, bo ch l mn hc
nghip v ct li, c ging sau khi ngi hc c nhng kin thc c bn v
cc mn hc c lin quan.
Trong khi hc bo ch, ngi hc cn c kh nng phn tch v tch hp kin
thc p dng c vo lnh vc bo ch, cn kt hp tt gia l th u y t v thc
hnh, ly l thuyt soi sng, gii thch cho thc h n h v dng thc h n h m inh
ho, b sung cho l thuyt.

18
II. I CNG V SINH Dc HC
1. Mt s khi nim hay dng

1.1. K h i nim v sin h duc h c (SDH)

Nh trn trn h by, vo u nhng nm 60, trn th gii nn cng

nghip dc phm ph t trin nhanh chng. Nhiu hng sn xut thuc ra i
v ua nhau a ra th trng nhiu bit dc khc nhau p ng nhu cu ca
ngi tiu dng.
Vo thi k ny, k th u t phn tch hin i cng hnh th n h cho php
thy thuc theo di c s" phn ca dc cht trong c th qua qu trn h dc
ng hc (hp th u - phn b" - chuyn ho - th i tr).
Chnh t cc bit dc khc nhau, thy thuc v ngi bnh p h t hin ra
rng: Nhiu bit dc tuy cha cng hm lng ca mt dc cht, nhng tc
dng lm sng li khng ging nhau. Th d:
- Cng l vin nn cha 0,5g aspirin nhng ca nh sn xut ny khi ung
tc dng gim au r t tt, cn ca hng khc th tc dng li khng r.
- Nang cloramphenicol, nang tetracyclin,... ca mt s" hng bo ch khi
ung khng c tc dng lm sng.
Vn dng th n h tu ca dc ng hc, ngi ra t vn nh gi kh
nng hp thu dc cht t nhng bit dc ni trn trong c th. Kt qu nghin
cu cho thy cc ch phm c hiu qu iu tr thp l do dc cht c hp th u
qu t. Th d:
Nm 1961, Levy v cng s chng minh vin aspirin khng c tc dng
gim au l do lng dc cht trong mu ch bng 1/2 vin i chiu.
Nm 1968, Glazko v cng s cho bit nang cloramphenicol ca 3 hng sn
xut khc nhau lu h n h trn th trng M khng c tc dng khng sinh l do
nng cloramphenicol trong m u ch bng 1/4 vin i chiu ca hng sng ch
Pfizer.
Nhng kt qu nghin cu ny thc y cc nh khoa hc y dc i su
vo nghin cu cc yu t" nh hng n qu trn h gii phng v hp th u dc
cht ca dng thuc trong c th, lm c s cho vic hnh th n h nn mt mn hc
mi: Mn sinh dc hc bo ch (biopharmaceutics) vi cc nh sng lp nh Levy,
Wagner, Nelson, Higuchi,...
N h vy, sinh dc hc l mn hc nghin cu cc yu t thuc v lnh vc
bo ch v thuc v ngi dng thuc nh hng n qu trnh hp thu dc cht
t mt ch'phm bo ch trong c th nhm nng cao hiu qu iu tr ca ch
phm .
Trn thc t, nghin cu SDH l nghin cu s" phn ca ch phm bo ch
trong c th, gn k th u t bo ch (yu t' dc hc) vi ngi bnh (yu t" sinh
hc). Do , SDH c coi l vng giao thoa gia 2 lnh vc: k th u t bo ch v
dc ng hc.

19
 Theo Benet, ni mt cch tng qut "SDH l khoa hc a thuc vo c th
Thuc phi c dng cho ngi bnh di mt dng bo ch ti u v cch dung
thch hp pht huy cao n h t hiu qu iu tr, m bo an ton, kinh t.
Nh trn ni, ni dng ca SDH gm 2 lnh vc: sinh hc v dc hc. i
su nghin cu cc yu t" sinh hc thuc v ngi dng thuc (nh gii tnh, la
tui, ng dng, ch liu,...) thuc v mn SDH lm sng (climcal
biopharmacy). Trong khi SDH bo ch ch yu tm hiu nh hng ca cc yu
t dc hc (nh dc cht, t dc, k th u t bo ch,...) n qa trn h gii phng,
hp thu dc cht trong c th.
Khi a mt dng thuc vo c th, mun gy c p ng lm sng, trc
ht dc cht phi c gii phng khi dng thuc v ho tan ti vng hp thu.
- Dc cht
- T dc
- K thut bo ch

S 1.1: Qa trnh sinh dc hc ca dng thuc

Nh vy, qu trn h SDH ca mt dng thuc trong c th gm 3 giai on:

Gii phng (Liberation) - Ho tan (Dissolution) - Hp th u (Absorption) (vit t t l
L.D.).
- Gii phng-, l bc m u cho qu trn h SDH. Khng c gii phng th
s khng c ho tan v hp thu. Th d: vin bao tan trong rut, nu v bao khng
r trong ng tiu ho th dc cht s khng c hp thu.
S gii phng dc ch t khi dng thuc ph thuc vo t dc, vo k
th u t bo ch, vo mi trng gii phng. C nh ng dc ch t ch c hp
th u tt mt vng n h t nh trong ng tiu ho, nu dc c h t khng c
gii phng ti vng hp th u ti u ny th lng hp th u s b gim .
- Ho ta n : dc ng hc chng minh, mun c hp th u qua mng
sinh hc, dc cht phi c ho tan ti vng hp thu. Nh vy, s hp th u
y ph thuc vo 2 yu t: qu trn h gii phng dc cht trc v c im
mi trng ho tan. Nhng dc cht t ta n thng c vn hp th u v chnh
bc ho tan l bc hn ch qu trn h hp thu.
- Hp thu: tc v mc hp th u ph thuc vo qu trn h gii phng v
ho tan ca dc cht ng thi ph thuc vo c tn h hp th u ca dc cht,
vo c im ca vng hp thu. Nh vy theo quan im SDH vi mt dc cht
n h t nh, nh bo ch c th ch ng tc ng vo qu trn h gii phng v ho
tan dc cht nhm iu tit qu trn h hp th u lm tng hiu qu iu tr ca
thuc. y cng chnh l mc ch ca SDH bo ch.

20
1.2. K h i nim v sin h kh dng (SKD)
nh gi qu trn h SDH ca dng thuc, ngi ta dng khi nim sinh
kh dng.
SKD l i lng ch tc v mc hp th u dc cht t mt ch phm
bo ch vo tun hon chung mt cch nguyn vn v a n ni tc dng.
Nh vy, thuc tim tnh mch c coi l c SKD 100%. Mt vin nn
vitam in c c cng hm lng vi thuc tim tnh mch, nu khi ung ch c 70%
vitam in c c hp thu vo tun hon th SKD ca vin nn so vi thuic tim
tnh mch l 70%.
Thc ra, hiu qa iu tr ca thuc ph thuc vo lng dc cht ti ni
tc dng (c quan ch). Hin nay, do cha c kh nng nh lng c dc cht
ti c quan ch, nn theo quan im dc ng hc ngi ta da vo nng
dc cht trong m u nh gi hiu qu iu tr ca thuc trn c s cng nhn
c s tng quan ng bin gia nng dc cht trong m u v ni tc dng.
Nh vy, do phn nh nng dc cht trong m u nn SKD gn lin vi tc
dng lm sng ca thuc (s 1 .2 ).

Thuc ti
ni dng
Hp
(Ngoi
ng tnh Thu
mch)

S 1.2: Qu trnh hp thu, phn b v thi tr ca dc cht t

dng thuc sau khi dng

21
 Khi nim SKD u tin c p dng cho cc dng thuc r n dng ung
(nh vin nn, nang cng), trong dc cht c hp th u qua ng tiu hoa.
Dn dn, vic nh gi SKD c tin h nh vi c cc dng thuc m dc cht
khng hp thu (nh thuc m dng ngoi, thuc nh mt...). Trong trng hp
ny ngi ta nhn m nh n tc v mc gii phng dc ch t khi dng
thuc v a ti b m t tc dng.
Nh vy, da trn SKD ta c th a ra nh ngha chnh xc hn v SDH
nh sau: "SDH l mn hc nghin cu cc yu t nh hng n SKD v cc bin
php nng cao SKD cho cc dng thuc". y chnh l ni dung c bn ca bo
ch hc hin i.
Nh trn trn h by, cc yu t" nh hng n SKD ca thuc c chia
th n h 2 nhm:
- Nhm cc yu t sinh hc: bao gm cc yu t thuc v ngi dng thuc,
trong SDH bo ch quan tm nhiu n h t n ng dng. V trong SDH,
ng dng chnh l mi trng gii phng - ho tan v hp th u ca duc cht.
- Nhm yu t'dc hc: bao gm cc yu t' thuc v dc cht (thuc tnh
l - ho, c tnh hp thu,...), v t dc, v k th u t bo ch, v bao b, bo qun.
Bin php c bn nng cao SKD ca ch phm bo ch l trong qu trnh
thit k dng thuc, xy dng cng thc bo ch phi xem xt nh hng ca t t
c cc yu t" ni trn n kh nng gii phng - ho tan v hp th u ca dc cht
nhm tm ra cng thc bo ch t u p h t huy cao n h t hiu qu iu tr ca
thuc, hn ch tc dng khng mong mun.

1.3. K h i nim v tu n g ng

tin so snh, nh gi cht lng cc ch phm bo ch, ngi ta a ra

mt s khi nim v tng ng. SDH bo ch quan tm n cc loi tng
ng sau:
- Tng ng bo ch (pharmaceutical equivalence): ch hai hay nhiu ch
phm bo ch cng loi t cc tiu chun cht lng qui nh, cha cng mt
lng dc cht.
- T h phm bo ch (pharmaceutical alternatives): ch hai hay nhiu ch
phm bo ch cha cng mt dc cht nhng khc nhau v dn cht (dng mui,
ester,...) hoc v hm lng, v dng thuc.
- Tng ng sinh hc (bioequivalence): ch hai hay nhiu ch phm bo
ch (tng ng bo ch hoc th phm bo ch) c tc v mc hp thu
dc cht nh nhau (c SKD ging nhau) trn cng i tng v iu kin th.
- Tng ng lm sng (clinical equivalence): ch hai hoc nhiu ch
phm thuc to nn p ng dc l nh n hau v kim sot c tri u chng
bnh mc ging nhau.
T trc n nay trong bo ch quy c ngi ta thng quan tm n tng
ng bo ch, nhng hai ch phm tng ng bo ch, cha chc c SKD

22
nh nhau v do cha chc to ra c p ng lm sng ging nhau. iu
chng t tng ng bo ch cha phn nh c cht lng dng thuc, cho
nn trong bo ch hin i, ngi ta a ra ch tiu cht lng mi l tng
ng sinh hc phn nh hiu qu tc dng ca thuc. Ch c hai ch phm tng
ng sinh hc mi c dng thay th cho n hau trong iu tr.

2. Cch nh gi sinh kh dng v ngha trong bo ch' v hng dn s

dng thuc

SKD c nh gi theo tng bc ca qu trn h SDH. Vic nh gi SKD

ch p dng cho cc ch phm cha dc cht thng c vn v SKD (nht l
cc dc cht t tan)

2.1. S in h kh dng in vitro

SKD in vitro nh gi qu trnh gii phng, ho tan c cht t dng thuc.

Test u tin nh gi bc gii phng dc cht t dng thuc l r ca
vin nn (c a vo Dc in M t 1950). Tuy nhin qua nghin cu ngi
ta nhn thy rng r cha phn nh c s hp th u in vivo ca thuc. T
1951 Edward lm thc nghim v ho ta n vi vin nn aspirin v cho rng tc
dng gim au ca aspirin ph thuc vo tc ho ta n ca dc cht trong
ng tiu ho. Tip Levy v Hayero chng m inh s tng quan t l th u n
gia ho tan v hp th u ca mt s' vin aspirin lu h n h tr n th trng.
Nhng nm sau , hng lot th it b nh gi tc ho tan ra i t c
s cho vic p h t tri n mn SDH bo ch. Nm 1958, Levy a ra th it b l quay.
Nm 1968 Pernarow ski gii thiu th it b gi quay v nm 1969 th i t b cnh
khuy ca Poole c a vo s dng.
Trc tn h hnh hng lot cng trn h nghin cu cng b" v s lin quan
gia tc ho ta n v tc dng ca thuc, nm 1970 Dc in M (USP 18) a
chuyn lun "th ho tan" (dissolution test) vo Dc in p dng cho cc dng
thuc rn vi 3 loi my: My 1 (gi quay), my 2 (cnh khuy) v m y 3 vi 6
chuyn lun vin nn v nang thuc c quy nh gii h n ho tan. Sau khi c
quy nh ca Dc in, cc nh sn xut c gng hon th in th i t b th ho
tan theo xu hng chung l m phng iu kin in vivo (nhit , pH, nhu
ng,...), gim nh sai s do th i t b gy ra v t ng ho qu trn h thao tc.
n nay, Dc in M 24 a ra 7 loi th i t b th ho tan. H u h t cc
vin nn v nang thuc cha dc cht t tan u c quy nh v gii hn ho
tan dc cht. Mi dng thuc c nhng th i t b nh gi ho ta n khc nhau.
Sau y l hai loi th i t b th ho tan dng cho vin nn, nang thuc v mt s
dng thuc rn khc.

23
2.1.1. Cu to thit b thho tan (dissolution tester)
a. M y gi quay (rotary basket):

Hnh 1.1. S my 1 (my gi quay)

Gm 3 b phn chnh (hnh 1 . 1):

- 1 cc y bn cu, dung tch 1 lt cha mi trng ho tan, c np y
hn ch bay hi nc.
- 1 b iu nhit c my khuy

- 1 gi quay cha m u th gn vi m t quay.

b. My 2: My cnh khuy (paddle)

Ging my 1 , ch khc l thay gi quay bng cnh khuy (hnh 1.2)
Vic dng my no l tu thuc vo tnh cht ca dc cht v dng thuc.
Nang cng v nhng vin nn c t trng thp, r chm c th dng m y 1
trn h mu th ni ln m t nc. My 2 dng cho hu h t cc loi vin nn.

24
 Ly mu

Mi trng
ha tan

Cch khuy

B iu nhit

Hnh 1.2. S my 2 (My cnh khuy)

2.1.2. iu kin th ho tan

- Mi trng ho tan: thng l nc ct 37c 0,5c loi khng kh.

Tu theo c im ho tan ca dc cht, khi cn c th dng h m phosphat
pH 4 - 8 hoc acid hydrocloric long (0,001 - 0,1N). Dung tch thng dng 500-
lOOOml (khng nh hn 3 ln nng bo ho ca dc cht). Mt s' cht lm
tng tan (nh cht din hot) c th cho thm vo mi trng ho tan.
- Thi gian th: thng l 30 - 60 pht ( 2%) vi lng dc cht ho tan
nm trong gii hn 70 - 80%.
- Tc khuy-, thng l 100 vng/pht vi my 1 ; 50 vng/pht vi my 2.
- im ly m u : nm gia khong cch t m t trn ca cnh khuy ti
m t nc trong cc, cch th n h cic khng di lcm.
- Phng p h p nh lng', do hm lng dc cht trong mi trng ho
tan thp nn thng dng phng php o quang ph hp th. My o quang c
th c ni vi my ho tan xc nh trc tip hm lng dc cht mt cch
t ng.
- Chun ho my: dng vin chun loi r v khng r ca Dc in M
(vin acid salicylic v vin premson).

25
2.1.3. Cch th v nh gi kt qu
Cho mi trng ho tan c qui nh vo cc, un nng n 37c. Cho
mu th vo cc (ch trn h bt kh trn b m t mu) v cho m y chy tc
qui nh. Ly m u th (b sung mi trng ho tan nu cn) v nh lng dc
cht theo m t trong chuyn lun. Cch nh gi kt qu ph thuc vo tiu
khun:
Tiu chun Dc in: Trong Dc in, ngi ta quy nh gii h n dc cht
ho tan ti thiu (Q), sau mt khong thi gian n h t nh (30, 45, 60 pht).
- Dc in Vit Nam III (2002) qui nh th tr n 6 vin, khng c c
vin no gii phng thp hn 70% lng dc cht quy nh. Nu c 1 vin khng
t th th tip ln 2 vi 6 vin khc v 6 vin ny u phi t yu cu..
- Dc in M qui nh th giai on u vi 6 vin, nu khng t th
th tip giai on 2 vi 6 vin khc v tnh kt qu trn 12 vin. Nu giai on 2
vn cha t th th giai don 3 v tnh kt qu trn 24 vin theo bng sau:

Giai on S n v th (vin nang) Gii hn ho tan

1 6 Mi n v > Q + 5
2 6 Trung bnh ca 12 n v > Q
Khng n v no < Q - 15
3 12 Trung bnh 24 n v > Q
Khng qu 2 n v < Q - 15
Khng n v no < Q - 25

- Dc in Trung Quc quy nh th 6 vin; sau 45 pht nh gi nh sau:

Trong 6 vin tng vin u > Q (70%)
+ Nu c 1 - 2 vin < Q nhng khng nh hn Q - 10 m tru n g bnh ca 6
vin > Q th vn t.
+ Nu c 1 vin < Q - 10 th th vi 6 vin khc.
+ Nu trong 12 vin c 1 - 2 vin < Q - 10 nhng tru n g bnh 12 vin > Q
th vn t.
Tieu chuan nh san xut: khi ng k thuc, nh sn xu t thng xy dng
th hoa tan dc chat theo thi gian. Vic dng thi cho php nh gi c th
hn tc ho tan dc cht v s ng n h t gia cc vin th.

2.1.4. ngha ca sinh kh dng in vitro

- SKD in vitro cha phi l SKD thc s, do cha phn nh c y
hiu qua lm sng ca ch phm th. C nhng trng hp dc ch t ho tan
nhanh, nhng cha chc c hp thu tt. Tuy SKD in vitro c bt chc mt

26
s iu kin sinh hc nh trn trn h by, nhng cn xa vi iu kin thc t
tr n c th sng.
- SKD in vitro l cng c kim sot cht lng cc dng thuc rn ung
(vin nn, nang thuc, thuc bt, pellet,...), c bit l m bo s ng n h t
cht lng gia cc l m sn xut, gia cc nh sn xut.
- SKD in vitro dng sng lc, nh hng cho nh gi SKD in vivo: Vic
nh gi SKD in vivo r t t tin, tn km, khng th lm tr n lan do trc
ht phi dng SKD in vitro sng lc, nh hng cho vic th in vivo gim bt
chi ph, thi gian.
- SKD in vitro dng thay th cho SKD in vivo trong trng hp chng
minh c c s tng quan ng bin gia SKD in vitro v in vivo vi iu kin
cng thc v qui trn h sn xut khng thay i. Thc ra do tn km nn SKD in
vivo thng ch c nh gi mt ln khi lp h s xin php sn xut: T v
sau phi dng SKD invitro kim sot qu trn h sn xut, m bo tn h n nh
cho SKD in vivo.
- SKD in vitro l cng c c bn xy dng cng thc, th it k dng thuc
trn c s coi t l ho tan dc cht l thng s cht lng ca u ra, t la
chn c dng thuc v cng thc bo ch ti u.

2.2. S in h kh dng in v ivo v vn tng ng sin h h c (TSH)

2.2.1. Quy nh v nh gi sinh kh dng in vivo

SKD in vivo nh gi giai on hp thu dc cht t ch phm bo ch.
Hin nay, nhiu nc trn th gii c cc tiu ban chuyn mn nh gi
SKD v TSH v a ra cc quy nh hoc hng dn v vic nh gi SKD v
TSH (nh M, C anada, Cng ng chu u, A ustralia...).
Theo quy nh b sung 1984 ca M, c th nh gi SKD bng cc phng
php sau (xp theo th t chnh xc, nhy, lp li gim dn):
la . Th in vi vo ngi bng cch xc nh s bin thin nng dc cht
hoc cht chuyn ho trong mu, huyt tng, huyt th an h hoc cc
dch sinh hc thch hp khc theo thi gian.
lb. Th in vitro c chng m inh l tng quan t l th u n vi s' liu
SKD in vivo trn ngi.
2. Th in vivo ngi bng cch o dc cht hoc cht chuyn ho bi tit
trong nc tiu theo thi gian.
3. Th in vivo ngi bng cch o tc dng dc l ca dc cht hoc cht
chuyn ho theo thi gian nu tc dng c th o c mt cch
chnh xc, nhy v lp li.
4. So snh tc dng lm sng mt cch thch hp
5. Nhng phng php c bit khc (c quy nh ring)

27
 SKD c nh gi trn ngi hoc sc v t th nghim nn s dao ng gia
cc c th thng l kh ln. V vy khi nh gi cn c cng quy nh r cac
iu kin nh gi nh:
- i tng th : ngi tnh nguyn kho m nh, tt n h t l gii, c
n ung v sinh hot theo ch quy nh (nhn n qua m t n h t 10 gi trc
khi dng thuc v 2 gi sau khi dng thuc). Ngi tnh nguyn phi c kim
tra k v cc hng s sinh l, sinh ho trc khi th thuc v phi c thng bo
y v mc tiu, phng php th, nhng quyn li v nguy c c th c (nh
phn ng ph ca thuc). Phi c nhng tho th u n bng vn bn gia ngi
tnh nguyn v ngi nh gi theo ng cc quy ch v th thuoc tr n ngi.
Nguyn tc la chn ngi tnh nguyn l gim nh dao ng gia cc c th, chi
dng s lng ngi mc ti thiu cn thit.
- Ly m u th : nu th trn m u th s lng m u phi c tr n g cho
pha hp thu v pha th i tr, xc nh c nh nng v cho php xc
nh c din tch di ng cong ca th t n h t 3 ln thi gian bn thi
ca dc cht. Nu th liu n theo phng php th i t k cho th thng ly
10 - 15 mu.
- M u i chiu: phi t cc tiu chun quy nh nh: phi l m u
c xt duyt cp giy php sn xut v lu hnh trn c s c th lm
sng. Tt nht l dng sn phm gc ca nh p h t minh hoc sn phm c uy tn
trn th trng.
- B tr th nghim v x l kt qu: thng dng phng php th i t k
cho ngu nhin. Ngi tnh nguyn (thng l 12 - 24 ngi) c chia th n h 2
nhm ung thuc 2 ln. Mi ngi trong nhm chn ngu nhin 1 trong 2 sn
phm (th hoc i chiu). Thi gian gia 2 ln dng thuc t n h t bng 5 ln
thi gian bn thi (t 1/ 2 ) ca dc cht m bo thuc ca ln dng trc
c o tho ht ri mi dng thuc ln th 2 . S liu th u c c x l bng
phng php thng k. Phng php x l nh hng nhiu n k t qu, do
cn c quy nh r trong cng nh gi SKD v TSH.

2.2.2. Cc thng s nh gi sinh kh dng in vivo

Khi phn tch th nng m u nh gi SKD in vivo ngi ta thng

xem xt 3 thng s* dc ng hc:
- Din tch di ng cong (DTDC) (vit t t theo ting Anh l AUC)
DTDC biu th mc hp thu ca dc cht t ch phm (hnh 1.3), c th tn h
theo phng php tch phn trn my tch phn:

DTDC = c.dt
0

(C nng dc cht trong m u ti thi im t)

28
 6 -I

5-

= 4 -
E

u 2-

1-

2 4 6 8 10 12
t(h)

Hnh 1.3. Din tch di ng ca th nng dc cht trong mu

Trong thc t, ngi ta c th tnh ton n gin hn theo quy tc hnh thang
(hnh 1.4).
DTDC c tnh theo cng thc:

DTDC0_>X=

(Trong Cn l nng dc cht ti im ly m u cui cng. Ke l hng s"

tc th i tr tnh t dc ca th logarit)

6 -

5-

0
0 4 8 12 16 20 24
t(h)

Hnh 1.4. M hnh tnh din tch di ng cong theo quy tc hnh thang

29
 - Nng cc i (Cmax): nng cc i th hin cng tc dng ca
thuc. Thuc c hp th u cng nhiu v cng nhanh th cng d t nng cc
i. Nng ny phi vt qua nng ti thiu c tc dng th thuc mi the
hin c p ng lm sng. Tuy nhin nu nng cc i vt qu nng an
ton ti thiu th thuc d gy tc dng khng mong mun.
- Thi gian t nng cc i (tmax): th hin tc hp th u c ch t t
dng thuc, t max cng ngn tc l thuc c hp th u cng n h an h v cng chng
t nng iu tr. Tuy nhin thuc hp th u nhanh th thng th i tr n h an h
do thi gian iu tr khng di.
Khi nh gi SKD, phi xem xt ng thi c 3 yu t trn th mi nh gi
y mc v tc hp th u dc cht t ch phm th. C th c 2 ch phm
c DTDC nh nhau nhng do tc hp th u khc n hau nn tc dng lm sng
khc nhau (hnh 1.5).

T h i gian (h)

Hnh 1.5. th nng mu ca hai ch' phm A v B

Khi nh gi tng ng sinh hc, tu ch phm i chiu m ta c 2 loi

SKD in vivo.
SKD tuyt i c xc nh khi so snh DTDC ca ch phm th vi
dung dch tim tnh mch (t.m) cha cng liu dc cht vi ch phm th, v
thuc tim tnh mch c xem l c SKD 100%.

30
 DTDCth x Dt m
SKDtuyt di = ______------ ----- X 100%
DTDCt m X Dth
Nu liu ca 2 ch phm nh nhau v trng lng ngi th thuc bng
nhau th:
DTDCth
SKDtuvtdi = --------------- X 100%
DTDCtm
Trn thc t, ngi ta hay dng SKD tng i khi ch phm i chiu l
thuc ung.
DTDCth
SKDtungdi = ------------------------------ X 100%
D T ^D
DPVyi- ch i u (th u -c -
ung)

Nu ch phm th c SKD = 80 - 125% so vi ch phm i chiu th c

coi l tng ng sinh hc vi ch phm i chiu.

2.2.3. ngha ca sinh kh dng in vivo

- Vi cc dng thuc rn ung, trong phn ln trng hp, nng dc
cht trong m u th hin p ng lm sng ca thuc. Do SKD in vivo phn
nh c hiu qu iu tr ca thuc. Nng cao SKD chnh l nng cao hiu lc
tc dng ca ch phm. nh gi SKD m bo quyn li ca ngi tiu dng,
gip cho ngi bnh la chn c thuc tt.
- Trong lm sng nh gi SKD in vivo thc cht l xc nh TSH nhm
gip cho thy thuc la chn c ng ch phm thay th. Ch c nhng ch
phm tng ng sinh hc vi nhau mi dng thay th c cho n hau khi iu
tr cho ngi bnh. Hin nay trn th trng c r t nhiu bit dc ca cc nh
sn xut khc n h au u xut pht t mt dc cht gic, nu khng nh gi SKD
th khng bit c thuc tt thuc xu, khng c c s la chn, thay th, hiu
chnh liu.
- nh gi SKD s thc y cc nh sn xut phn u nng cao cht
lng sn phm ca mnh, m bo c s ng nht gia cc l m sn xut,
gia cc nh sn xut vi nhau.
- Vic nh gi SKD th hin bc tin v cht ca k th u t bo ch, nh
du s chuyn t bo ch quy c sang bo ch hin i. Trong bo ch hin i,
k th u t bo ch gn vi hiu qu lm sng ca dng thuc. Dng bo ch c
coi nh mt h cung cp thuc (drug delivery system s) trong c th, trong dc
cht c gii phng mc ti a v vng hp th u ti u. Trong bo ch hin
i, ngi dc s i su vo xy dng cng thc, th it k dng thuc, kim sot
qu trn h sn xut nng cao SKD ca thuc, ng thi c vn cho thy thuc
v ngi bnh la chn thuc hp l, an ton v hiu qu.

31
2.3. Tng quan gia sin h kh dng in vitro v in vivo

V nh gi SKD in vivo kh tn km, nn cc nh nghin cu c gng tm

s tng quan ng bin gia SKD in vitro v in vivo vi hy vng c th dng
SKD in vitro thay cho SKD in vivo trong nh gi TSH. Mt trong nhng
phng hng nghin cu l c gng lm cho iu kin th in vitro ngy cng gn
vi th in vivo nh ni trn. Tuy nhin du sao th nhiu yu t in vivo tc
ng n kt qu nh gi cng kh m th hin c trong th in vitro (tc ng
ca h men ng tiu ho, chuyn ho qua gan, tho rng d dy, tng tc
thuc - thc n, s hp thu qua m ng sinh hc...)- Do trn thc t khng th
dng SKD in vitro thay th mt cch n th u n cho SKD vi vivo m phi nghin
cu k tng trng hp c th.
Theo tng quan ti liu ca B anakar v Block, trong vng 20 nm (t 1962 -
1982), cc nh nghin cu nghin cu tng quan in vitro - invivo ca mt s
ch phm bo ch ca 50 dc cht, trong c 30 dc cht th hin tng quan
t l thun; 4 dc cht ch c tng quan ng bin mc n h t nh, cn 16
dc cht cn li r t t tng quan. Kt qu nghin cu cho th y s tng quan
ng bin thng th hin cc dc cht t tan, trong ho tan l bc hn ch
hp thu.
Dc din M trong ph lc v nh gi SKD in vitro v in vivo c cp
n 3 mc tng quan in vitro - in vivo: mc A, B v c , trong mc A l mc
tng quan ng bin cao nht. Trong trng hp chng m inh c s tng
quan t l th u n th c th dng SKD in vitro thay th cho SKD in vivo. Cn ni
chung th SKD in vitro ch l cng c d on SKD in vivo v kim sot s
ng n h t v cht lng ca sn phm gia cc l m sn xu t khc n h a u v gia
cc nh sn xut khc nhau nh ni trn.

3. Cc yu t thuc v dc cht nh hng n sinh kh dng

Nh trn trnh by, c nhiu yu t' nh hng n SKD ca dng thuc.

Tuy nhin, mc nh hng th mi dng thuc c mt c tr n g ring v s
c trnh by k tng dng, y ch trn h by mt s n t chung v nh hng
ca dc cht v ngi dng n SKD.

3.1. Thuc tnh l ho ca duc cht

3.1.1. tan v tc ho tan

Trong c th, mun c hp thu th dc cht phi c ho tan trong dch sinh
hc bao quanh mng. Do , ho tan ca dc cht nh hng nhiu n SKD.
Vi dc cht t tan th chnh tan l yu t hn ch hp thu. Theo cc nh
nghin cu th chnh cc ch phm cha dc cht t tan ( tan < 1%) thng c
vn v SKD. Trong trng hp ny, mun tng SKD cua thuc th phai tm
bin php lm tng tan ca dc cht (dng cht lm tn g tan, dng hn
hp dung mi, ch h phn tn rn...).

32
 Vi dc cht d tan v hp thu, khi ung d gy tc dng khng mong
mun hay c tnh do nng nh vt qu gii hn an ton. Trong trng hp
ny, ngi ta phi lm chm qu trn h gii phng v ho ta n ca dc cht ko
di tc dng ca thuc v lm gim tc dng ph.
Tc ho tan ca dc cht theo phng trn h Noyes - W hitney c biu
th nh sau:

= K .A (C s-C )
dt
Trong : K l hng s' tc ho tan
A l din tch b m t tip xc ca dc cht vi mi trng ho tan
Cs l nng bo ho ca dc cht
c l nng dc cht ti thi im t.
D
Nu thay K = ------ th ta c phng trn h N erst - B runer
h

^ ( C s - C )
dt h

Trong : D l h skhuch tn ca dc cht

h l b dy lp khuch tn
Trong bo ch, vi dc cht rn t tan ngi ta lm tng tc ho tan bng
cch gim kch thc tiu phn (nghin mn hn) lm tng tc hp thu.
Tuy nhin, trong c th, ho tan v hp th u l mt qu trn h ng. Khi dc
cht va c ho ta n th c hp th u ngay, lm cho hiu s" Cs - c lun lun
tn ti, do lm cho qu trn h ho tan din ra lin tc (s 1.3).

M i ng ho tan
Mng hp thu

S 1.3. Qu trnh ho tan - hp thu dc cht

33
 Tm li, c th ni mt cch tng qut: t t c cc yu t nh hng n
tan v tc ho tan ca dc cht u c kh nng n h hng n SKD cua
dng thuc. Tm cc bin php tc ng ln tan v tc ho ta n l mt hng
i ci thin v nng cao SKD.

3.1.2. Trng thi kt tinh hay v nh hnh .

Dc cht rn c th tn ti di dng kt tin h hay v nh hnh. T rng th i
vt l ny nh hng n tan v bn ca dc cht, do nh hng trc
tip n SKD ca thuc. Dng kt tinh l dng c cu trc m ng li tin h th
tng i bn vng, cho nn thng kh ho tan hn dng v nh hnh. Cng
mt liu dc cht, nhng dng v nh hnh do d ho ta n hn nn c kh nng
to ra SKD cao hn dng kt tinh. Th d:
Vi novobioxin, dng v nh hnh d tan hn dng k t tin h 10 ln. Th
nghim trn ch, khi cho ung cng 1 liu dc cht, vi dng k t tin h th khng
pht hin c thuc trong mu, nhng dng v nh h nh th sau 1 gi t
nng nh mc kh cao (40mcg/ml) v sau 6 gi vn nh lng c novobioxin
trong m u (bng 1 . 1).

Bng 1.1: Nng novobioxin trong mu ch sau khi ung dng kt tinh v v nh hnh
(mcg/ml).

Gi Dngkt tinh Dng v nh hnh

0,5 Khng pht hin c 5,0

1 - 40,0
2 - 29,5
3 - 22,3
4 - 23,7
5 - 20,2
6 - 17,5

Khi ch hn dch, trong mi trng nc, novobioxin v nh h nh chuyn

th n h dng kt tinh, lm gim tan, do lm gim SKD ca thuc trong qu
trn h bo qun. Novobioxin c 2 dng mui: Mui n a tri v calci, trong mui
calci n nh hn. to ra c dng hn dch c SKD t b th ay i phi dng
dng mui calci v nh hnh, ng thi dng cc cht lm tn g nht mi
trng phn tn lm chm qu trn h thay i dng th hnh.
Vi cloramphenicol, tnh hnh cng tng t. Mui cloram phenicol dng
kt tinh sau khi ung do kh tan nn khng thu phn c gii phng li
cloramphenicol cho nn khng gy c tc dng iu tr. Khi ch hn dch phi
dng cloramphenicol palm itat hoc ste a ra t (dng mui p a lm ita t gii phng li
cloramphenicol nhanh hn).

34
 V vy, khi bo ch, ngi bo ch phi bit chnh xc dng th hnh cua
duc cht m bo SKD ca thuc.

3.1.3. Hin tng a hnh (polymorphisme)

Mt duc cht c th kt tinh di nhiu dng tin h th khc nhau tu theo
iu kin kt tinh. Cc dng kt tinh khc nhau c tnh cht vt l khc nhau.
Qu trn h kt tinh thng b t u t vic to th n h dng t bn cn t nng lng
n dng bn cn nhiu nng lng hn. Dng khng bn d tan hn dng bn, do
khi ch th n h dng bo ch, s c SKD cao hn. Tuy nhin, trong qu trn h bo
qun, dng khng bn c th chuyn th n h dng bn lm gim SKD ca thuc.
Th d: ngi ta ph t hin hn dch cloramphenicol palm itat lu h nh A ustralia
trong mt thi gian di khng c tc dng r r t trn lm sng. Khi nghin cu
tm hiu nguyn nhn cc nh SDH nhn thy rn g dc cht ny tn ti di 4
dng: Dng v nh hnh v 3 dng kt tinh A, B v c. Trong 3 dng kt tin h ch
c dng B l tan c. Khi ung, sau 2 gi dng B cho nng m u cao gp 10
ln dng A. Trong qu trn h bo qun hn dch, dng B chuyn sang dng A v
lm gim SKD ca ch phm.
Trong bo ch, c r t nhiu dc cht c hin tng a hnh, n h t l cc
corticoid (Bng 1.2).
Trong qu trn h bo ch, cc thao tc k th u t nh nghin bt, to ht, dp
vin, ch hn hp phn tn rn... u c th lm cho dc cht chuyn t dng
kt tinh khng bn sang bn lm gim SKD ca thuc. Ngay vi mt dng kt
tinh, hnh dng v kch thc tinh th cng c th thay i v nh hng n cc
thng s' k th u t bo ch nh trn chy ca bt, kh nng chu nn... Nhiu
khi cc khuyt t t tin h th (nh s st m, nt rn tinh th, cc khong trng
trong m ng li cu trc tin h th...) cng c th lm thay i ho ta n v hp
thu duc cht.

Bng 1.2. Dng kt tinh ca mt s dc cht hay gp

Dc cht Dng kt tinh Dc cht Dng kt tinh

Cortison acetat 5 Ribolavin 3

Progesteron 5 Sulphathizol 3

Aspirin 2 -7 Testosteron 3

Barbital 4 Novobioxin 2
Hydrocortison 4 Hydrocortison acetat 2
Prednisolon 3 Prednison 2
Cloramphenicol palmitat 3 Methyl prednison 2

35
3.1.4. Hin tng hydrat ho
Trong qu trn h kt tinh, duc cht c th dng k han hay dng hyd rat
ho. Dng khan hay ngm nc c lin quan n ho tan ca duc cht, do o
c th to ra cc ch phm tng ng v bo ch nhng li c SKD khc nhau.
Thng thng dng khan ho ta n trong nc n hanh hn dng ngm nc, cho nen
s c hp th u nhanh hn. Th d:
Ampicilin khan ho tan trong nc n hanh hn ampicilin trih y d rat. Nghin
cu SKD ca hn dch v nang thuc am picilin lu h nh trn th trng ngi ta
thy: Ch phm Omnipen (cha ampicilin khan) c SKD cao hn ch phm
Polycilin (cha lng tng ng am picilin trihydrat). Kt qu nghin cu v
th ho tan, v hp thu trn sc vt v trn ngi u ging nhau v ph hp vi
tan ca nguyn liu ban u (hnh 1 .6 ).

t (pht)

Hnh 1.6: th nng mu ca ampicilin trihydrat ch sau khi ung hn dch

Trong bo ch, nhiu dc cht tn ti di 2 dng: k h an v ngm nc:

cloral, cafein, penicilin, quinin, hydrocortison... Trong qu trn h sn xu t v bo
qun, di tc ng ca cc yu t nh nhit , dung mi (xt h t t, sy kh,
ch hn dch,...) c th lm cho dng ny chuyn sang dng khc dn n th ay i
SKD ca ch phm. Do vy, cn phi ch xem xt m bo tc dng ca thuc.

3.1.5. Kch thc tiu phn (KTTP)

Theo phng trn h Noyes - W hitney, tc ho ta n ca duc c h t p h

thuc vo b m t tip xc (BMTX) gia tiu p h n r n v mi trng ho tan .

36
 Trn thc t, vo u nhng nm 1970, ngi ta p h t hin mt s ch
phm lu hnh trn th trng khng c tc dng iu tr. i su vo nghin cu,
cc nh SDH chng minh rng nguyn nhn l do KTTP khng thch hp lm
cho duc cht khng ho ta n c. Th d:
Vin grisesofulvin dng bit dc Grifulvin V khng c tc dng chng nm.
Nguyn nhn l do vin c bo ch t bt mn. Alinson v cng s chng
m inh rng tc hp th u ca griseofulvin tuyn tn h vi logarit din tch BMTX
ca dc cht (hnh 1.7): 0,5g griseofulvin micronise cho mt nng m u tng
ng vi lg griseoulvin dng bt mn. Do kt qu nghin cu ny U SP
chp nhn griseofulvin siu mn vi liu dng gim i mt na so vi dng bt
thng thng.

30

25

20

q 15

10

5 1

0
0
K h o n g 1 JJT1

0.5 1 1.5
Khong 10 fim
2.5
lgA

Hnh 1.7. th biu th nh hng ca kch thc tiu phn ti sinh kh dng ca grisecfJvin

Trn lm sng, cc ch phm cha nortestosteron micronise c tc dng m nh

gp 5 ln cc ch phm tng ng nhng bo ch t dng bt mn.
Hin nay, nhiu duc cht c dng di dng bt siu mn nht l cc
corticoid: hydrocortison, dexamethason, luocinolon acetonid,... Dng bt siu mn
s gim c liu dng, tit kim c duc cht nn em li li ch kinh t rt ln.
Qua nghin cu SDH pht hin nhiu duc cht c tc hp thu ph
thuc vo KTTP nh: cloramphenicol, tetracylin, sulfathiazol, tolbutam id, aspirin,
barbituric...
Vi duc cht d b phn hu bi dch v, nu nghin mn qu duc cht s
d tan trong dch v v b phn hu nhiu hn (nh penicilin, erythromycin,...).
Vi duc cht c mi v kh chu, khi nghin mn qu s lm tng cng
mi. c th nh hng n hiu qu iu tr ca thuc.

37
 Trong mt s bt thuc hay hn dch, nu bt mn qu s d to nn cc vn.
Bi v vt cht lun c xu hng bo ton nng lng b m t nn cc tiu phn
siu m n c xu hng tp hp nhau li gim b m t t do. Trong cc cc vn
thng cha nhiu khng kh, lm cho duc cht kh thm mi trng ho tan,
cho nn lm gim tc ha tan v hp th u ca thuc. Khi nghin mn, bt cng
d h t m (do BMTX tng), do cng kh bo qun hn.
Ngoi ra, vic nghin bt mn, cng tiu tn nhiu nng lng v thi gian,
c th khng li v kinh t. Ngoi tc ho tan, KTTP cn nh hng n cc
thng s khc trong qu trn h bo ch nh trn chy ca bt, kh n ng lin ket
khi dp vin,... Cho nn cn phi xem xt KTTP mt cch ton din, trong tng
dng thuc c th.
Tm li, khi bo ch cc dng thuc c cha tiu phn duc cht r t t tan, cn
tiu chun ho KTTP cho tng ch phm m bo SKD ca thuc.

3.1.6. n nh ho hc ca dc cht
Nhiu duc cht khng bn v m t ho hc di tc ng ca ngoi mi b
oxy ho, thu phn, phn ging bi enzym, mi trng acid... (vitam in, aspirin...).
SKD ca cc ch phm bo ch t cc duc cht ny s b gim dn trong qu
trn h bo ch v bo qun. Do cc nh bo ch phi ch tm cc bin php
khc phc m bo SKD ca thuc (bao bo v, bao tan rut, vi nang ho...)-

3.2.c tnh hp thu ca duc cht v nhng bin i ho h c cn thit

3.2.1. c tnh hp thu ca dc cht

Trn thc t, phn ln duc cht c hp thu qua mng bng qu trnh khuch
tn th ng. Tc khuch tn qua mng tun theo nh lut Fick:

= 5 5 x S x ( c , - c 2)
dt 1
Trong :
K l h s phn b" ca dc cht gia mi trng v m ng
D l h s' khuch t n ca dc cht qua m ng
s l din tch BMTX gia mi trng v m ng
1 l b dy ca m ng
Cj - c 2 l chnh lch nng dc cht hai bn m ng
Vi mt loi m ng sinh hc n h t nh th cc thng s v m ng l khng
thay i. V vy, s hp th u ph thuc ch yu vo bn cht ho hc ca duc
cht, trong ng lu l:
H s phn b (HSPB) D / N ca duc cht: bn ch t m ng sinh hc l
lipoprotein. Cc duc cht ch th n nc, s kh phn b vo phn lipid ca m ng.

38
Ngc li, cc duc cht qu th n du s kh ho tan trong mi trng v d b
gi li trong phn lipid ca mng. Thc t cho thy, ch c nhng duc cht m
HSPB D/N tng cn bng mi d i qua mng. HSPB D/N thc nghim c
xc nh bng cch cho duc cht ho tan trong 2 dung mi thuc pha du v pha
nc (thng l octanol/nc), sau xc nh nng dc cht trong 2 dung
mi tnh HSPB K.

HSPB cho php d on kh nng khuch tn ca duc cht qua mng.

S ion ho ca dc cht: Cc dc cht c kh nng ion ho cao s kh i qua
c phn lipid ca mng, mc ion ho ca dc cht li ph thuc vo pH mi
trng: d dy, cc acid yu (pKa > 2,5) tn ti ch yu di dng khng ion
ho v c hp th u kh nhanh, cc base yu th ngi li, ch yu tn ti di
dng khng ion ho rut non v c hp th u .
Khi duc cht kh hp thu, ngi ta tin hnh bin i ho hc theo cc
hng; to mui hoc to ester.

3.2.2. To mui

Cc dc cht l acid yu v base yu t phn li, do t ho tan v t c

hp th u trong ng tiu ho. tng cng SKD ca cc dc cht , ngi ta
thng dng dng mui d ion ho.
Vi acid yu, khi bin th n h dng mui, s hp th u d dy tng ln r t
nhiu do to th n h vng micro pH. Theo Cadwallader, c ch tn g hp th u c
gii thch nh sau: (S 1.4).

Vng micro pH
/ (pH = 5 - 6)

Mng hp thu

S 1.4. Qu trnh hp thu acid yu d dy

39
 Cc tiu phn mui acid yu d tan trong nc, khi vo da dy lp phn t
b m t tiu phn s nhanh chng phn ly v ho tan vo lp nc bao q u a n h tiu
phn to ra mt vng micro pH (c pH 5 - 6 ) c tc dng nh mt h m tng
cng s khuch tn ca duc ch't. Cc phn t ion ho t lp khuch tn ny
khuch tn nhanh vo mi trng dch v v kt ta li di dng tiu phn siu
mn to ra BMTX ln nn acid yu nhanh chng ho tan li v khuch tn qua
mng. V d:
Vi penicilin V, dng dng mui kali hoc calci penicilin V cho nng mu
cao hn nhiu so vi penicilin V (hnh 1.8).

E
~5>
o

t(h )

Hnh 1.8. th hp thu ca penicilin V v dng mui ngi

Tuy nhin, c nhng trng hp khi dng dng mui d tan li gy tc dng
ph. cho nn vn phi dng dng acid. V d nh tolbutam id, khi dng dng mui
n atri do hp thu nhanh nn d gy h ng huyt t ngt trong gi u. khng
c li cho ngi bnh, trong khi . dng acid gim ng huyt u n trong
vng 10 gi. nn trong thc t, ngi ta vn dng tobutam id (hnh 1 .9 ).
Vi cc base yu. s hp thu rut cng tng ln khi dng dng mui. V d
nh tetracylin hydroclorid.
Mt s duc cht c bn cht l acid yu hoc base vu khi to mui s tng
tan nh: acic aminosalicylic. acid nalidicic, acid salicvlic. ampicilin. a sp in n .
barbituric. clorphem ram in. dextrom ethorphan, novobiocin. phenytoin
erythrom ycin, quimn, sulfamid. thiam in...

4fl
 t(h )

Hnh 1.9. th nng ng huyt ngi bnh sau khi

ung vin tolbutamid v natri tolbutamid.

3.2.3. To ester (cc tin thuc)

Mt s duc cht c chuyn th n h ester to ra cc tin thuc (pro - drug)
tng SKD. V d:
Erythrom ycin d b phn hu dch v, khi chuyn th n h ester vi acid bo
s khng tan trong dch v nn t b phn hu. n rut, di tc ng ca
esterase s gii phng tr li erthyrom ycin gy tc dng iu tr. Cloramphenicol
dng di dng p alm itat hay ste a ra t t tan nn gim c v ng, vo rut s
gii phng tr li cloramphenicol nh trng hp trn.
Prednisolon dng di dng n a tri hem isuccinat chm tan, s ko di c
tc dng ca thuc.

4. C c yu t 'th u c v n g i dng thu c nh hng n sin h kh dng

Thc nghim trn ng vt cng nh th thuc v kinh nghim dng thuc

trn ngi cho thy p ng vi thuc khc bit r t nhiu gia cc c th. Cng
mt liu dc cht, c th cho nhng nng m u i khi khc n h au xa gia cc
i tng dng thuc.
S khc n h au ny c th l do cc nguyn n h n bn trong nh tr n g th i
sin h l, bnh l... hoc do nguyn n h n bn ngoi nh iu kin ngoi cnh.

41
4.1. C c yu t 'sin h l

4.1.1. Tui: C hai i tng r t ng quan tm c s khc nhau r t ln so V1 ^

tui chung t 20 n 60, l tr em v ngi cao tui, cc tui ny c 8 .
thay i r t nhiu v cc thng s dc ng hc nh hp thu, chuyn hoa,
tr...
Tr s sinh v ang b:
tu n u sau khi sinh, phn ng ca tr vi thuc c bit nhy cm do
c tnh sinh l ring.
- V khuch tn: do s pht trin cha n nh, tn h th m ca m ng sinh
hc tr s sinh ln hn nhiu so vi tr em ni chung v c bit l so VI
ln. V vy, nhiu thuc c th i qua hng ro hp th u mt cch d dng va en
tu n hon chung gy qu liu v ng c. Ngay c cc thuc dng ti cho cung
c hp thu vo m u (neomycin, hexachlorophen,...).
- V chuyn ho: tr em, h men chuyn ho ch c p h t tri n hon
thin sau 3 thng tui. V vy, khi h men cha hon chnh th vic chuyn ho
hot ho thuc hoc chuyn ho kh c thuc khng thc hin c. V
vy, nhiu thuc tr nn r t nhy cm v d gy ng c vi tr s sinh (nh
barbituric, cloramphenicol, sulamid,...)-
- V thi tr: chc nng cc c quan th i tr nh gan, th n cha hon
thin nn thuc d tch lu gy qu liu. Chc nng lc ca th n ch n nh tr
3 n 14 thng tui, cho nn s th an h thi ca th n tr non km hn tr 2
tui 5 ln. Cc thuc c thi gian bn thi di (nh k h n g sinh) r t hay gy ng
c cho tr.
- Ngi ta khuyn nn c ch liu c bit cho tr s sinh (trong vng 15
ngy tui) v tr ang b (t 15 ngy n 30 thng). T rn 30 th n g do h rn g
p h t trin hon thin, vic n ung gn nh ngi ln cho nn tn h theo ch
tr em hi chung. I
Vi tr s sinh v ang b, trc ht phi tr n h dng thuc. N u buc phi
dng thuc th phi xem xt ch liu tht cn thn v c th, khng nn ch
da vo cc nguyn tc tnh liu chung, v m t bo ch, cn phi nghin cu cc
dng bo ch thch hp cho tui ny.

Ngi cao tui:

Vic lo ho km theo s suy gim chc nng ca t t c cc c quan trong c
th.
Chc nng hp thu gim lm cho mt s thuc khng liu tc dng ti thiu.
Vic suy gim chc nng gan dn n phi cn th n trong vic s dng cc
thuc chuyn ho qua gan ln u.
Suy gim chc nng th n km theo s gim th an h th i s lm chm vic
th i tr cc thuc nh digoxin, sulfam id v d dn n ng c.

42
 Vic suy gim chc nng th gic lm ngi cao tui kh c c nhn
thuc hoc t gii thiu thuc hoc ch in trn vin thuc, nang thuc (thng
c in c ch nh) kh phn bit c cc loi thuc c hm lng khc nhau.
Ngi cao tui cng kh nh ch liu, thi gian dng thuc, cch dng thuc do
gim tr nh.
Ngi cao tui cng kh ung thuc do gim tit nc bt v chc nng nut
nn hay b sc, b nghn, n h t l khi ung thuc vin, nang thuc do vin thuc to
v nang thuc hay b dnh vo thc qun.
Hin nay, nhiu loi thuic c ng gi kh chc chn tr n h tr em d
ly nhm thuc. iu ny trn thc t li gy kh khn cho ngi cao tui khi
phi t dng thuc, v sc yu tay run nn h li r t kh m bao b ly thuc.
Do tui th ngy cng c nng cao nn t l ngi cao tui trong x hi
ngy cng nhiu. Tui gi thng gn vi bnh t t cho nn y l mt i tng
dng thuc ng o. Tuy nhin, do c nhng c im ring v sinh l tc ng
n qu trn h dc ng hc, cho nn cn phi ch nghin cu cc dng bo ch
thch hp cho ngi gi m bo SKD v p ng lm sng ca thuic.

4.1.2. C thai

C thai lm thay i hm lng nc trong t chc, c th nh hng n s

phn b' thuc.
Ph n c thai thng thiu nng gan nht thi do hormon sinh sa. Do vy
phi cn thn khi dng cc thuc phn hu gan, nu khng thuc s tch lu n
nng gy c, khng nhng nguy him cho ngi m m cn c vi thai.
ph n c thai nhiu phn ng kh c gim: Cc qu trnh oxy ho, hydroxyl
ho gim i mt na. Progesteron, pregnadiol c ch men glucuronyltransferase
lm chm qu trn h lin kt glucoronic.

4.1.3. Th trng

Khi th trng mt ngi khc nhiu so vi tr's" tru n g bnh th cc ngn ca

c th c th nh hng nhiu n s phn b', tch lu thuc. Mt liu dc cht
nh nhau c th s phn b" tch lu khc nhau kh xa gia nhng ngi c hnh
th to nh khc n hau dn n tn h trn g khng liu hay qu liu. Tuy nhin,
vic tnh liu theo th trng nhiu khi cng cha tn h ht c tnh hp th u thuc.
Thuc th n du thng c nh trong cc m lipid; cho nn ngi bo nhiu m
m, nng thuc t do c th thp; trong khi , vi thuc th n nc th ngc
li cc ngn cha nhiu nc s kim sot qu trn h khuch tn, phn b" v
th an h th i ca thuic.
Tnh liu theo th trng cng cha tn h n cc yu t" tc ng nh h men,
lin kt protein, recepor c trng.

43
4.2. C c yu t bnh l

Gia cc c th kho m nh c s p ng khc nhau i vi thuc th

gia cc c th b bnh s khc nhau cng r nt hn, bi v vi c th b bnh
nhiu chc nng b tn thng.

4.2.1. Cc yu t' lm gim s hp thu thuc

Khi ung, s hp thu thuc c th gim do:
- Tng nhanh tc thuc i qua ng tiu ho, lm gim thi gian tip
xc ca thuc vi nim mc hp thu n h t l nim mc rut.
- Gim tit dch tiu ho; th d gim tit dch v s ngn cn ti hp thu
s t rut. Gim tit cc yu t ni lm gim hp th u B12. Gim ti t m t lm gim
ti hp th u vitam in K rut.

4.2.2. Cc yu t lm tng s hp thu thuc

mt s trng hp bnh l, s hp thu thuc li tn g do:

- Tn thng da hay nim mc hp thu
- Tn thng hng ro khuch tn: khi vim m ng no th penicilin v
streptomycin d dng khuch tn vo no v nh vy c th d dng t c
nng thuc iu tr hu hiu trong dch no - tu. Trong trng hp gim
protein huyt tng, nng thuc t do (dng khng lin kt vi p rtein huyt
tng) s tng c th dn n hin tng qu liu.
- Tn thng gan: vim gan, x gan chc nng lin kt glucoronic v lin
kt sulonic gim lm tng tch lu nhiu thuc trong c th. Vim gan virus lm
gim kh nng kh alcol trong nhiu nm.
- Tn thng thn: lm gim th an h thi th n dn n tch ly thuc trong
c th, c th dn n ng c. Tn thng th n thng ko theo s ri lon in
gii, nh hng n cc qu trn h dc ng hc. Do vy, tn thng th n phi
dng thuc cn th n v phi gim liu.

4.3. ng dng thuc

L mi trng gii phng, ho tan v hp th u ca dc cht, do nh

hng n SKD ca thuc v s c xem xt c th khi nghin cu SKD ca cc
dng thuc c th.

44
 Chng 2

DNG DCH THUC

MC TIU
1. Trinh by c c im, phn loi dung dch thuc, cht tan v dung mi.
2. Trnh by c k thut iu ch nc ct v nc kh khong.
3. Phn tch c cc yu t nh hng n tan v tc tan ca dc
cht, vn dng trong k thut iu ch dung dch thuc.
4. Trnh by c k thut iu ch cc dung dch thuc thng thng dng
ung v dng ngoi.

NI DUNG
I. I CNG V DUNG DCH THUC
1. nh ngha v c im
Dung dch thuc l nhng ch phm lng, c iu ch bng cch ho tan
mt hoc nhiu dc cht, trong mt dung mi hoc mt hn hp dung mi. Dung
dch thuc c th dng trong hoc dng ngoi.
Cc dng bo ch, xt v mt cu trc ho l, c coi l cc h phn tn.
Mt h phn tn bao gm cht phn tn v mi trng phn tn. khc vi pha
phn tn b phn chia gin on, mi trng phn tn m ang tnh cht lin tc.
H phn tn c chia lm 3 loi theo kch thc ca cc tiu phn tn nh sau :
H ng th (h phn tn phn t); H d th; H siu v d th (hay h phn
tn keo). th sau y minh ho cch phn loi trn.

Hnh 2.1. th biu din s ph thuc ca din tch b m t ring (S) trong h phn tn
theo kch thc tiu phn tn (a).

45
 th trn cho thy, v tr ca dung dch thuc trong h thng phn loi cc
dng bo ch theo h phn tn. Thc ra, dung dch thuc ni chung bao gm 3 loi
theo c tnh l ho, l dung dch tht, dung dch keo v dung dch cao phn
t. c tnh ca 3 loi dung dch ny c nu trong mn hc ho l- V d
nh dung dch th t v dung dch keo, c c im chung l trong sut, ng n h t
nhng khc bit l dung dch keo, c s tn x nh sng ca tiu phn phn tn
(hin tng c m khi chiu nh sng i qua). Dung dch cao phn t l trng
hp c bit nm ngoi cch phn loi trn, c c tnh chuyn th sol v th gel
mt cch th u n nghch. Cc tiu phn c kch thc ln hn 10 ln tiu phn keo
nhng khng phi l h d th m l h phn tn ng th (tiu phn phn t n l
phn t).

2. Phn loi dung dch

- Phn loi theo cu trc ho l: Dung dch thuc bao gm dung dch tht,
dung dch keo, dung dch cao phn t.
- Phn loi theo trng thi tp hp: Dung dch cht r n trong cht lng,
dung dch cht lng trong cht lng, dung dch cht kh trong cht lng.
Cn lu khi nim dung dch trong h phn tn c th mm v rn , l
khi nim m rng ngoi phm vi cc dng thuc lng. V d, thuc m
c cu trc dung dch. Trong ngnh dc, gn y p dng cc phng
php to ra dung dch dc cht rn t tan trong cc cht r n th n nc,
lm tn g tan ca dc cht, t tn g sinh kh dng ca cc dng
thuc rn.
- Phn loi theo bn cht dung mi: Dung dch nc, dung dch du, dung
dch cn.
- Phn loi theo xut x cng thc pha ch: Dung dch pha ch theo cng
thc quy nh trong Dc in, gi l dung dch dc dng. Cc dung
dch pha ch theo n ca bc s, gi l dung dch pha ch theo n.

3. u nhc im ca dung dch thuc

Dung dch thuc c dng nhiu n h t trong iu tr, so vi cc dng thuc

khc, do c nhiu u im, khi s dng di dng dung dch, dc cht c hp
thu nhanh hn so vi cc dng thuc rn, v trong dng thuc rn, dc cht phi
tr i qua giai on ho tan trong dch ca c th. Mt s dc cht dng dung
dch, khi tip xc vi nim mc khng gy kch ng nh khi dng di dng thuc
bt, thuc vin (natri bromid. n atri iodid. cloral hydrat,...).
Tuy vy, trong dung dch thuc, dc cht thng c n nh km. Cc
phn ng thu phn, oxy ho, racemic ho. phn ng to phc, cng nh s ph t
trin ca vi khun, nm mc. c th l nguyn nhn phn hu dc cht.

46
4. Thnh phn ca dung dch thuc
Dung dch c hai hp phn, thng c gi l dung mi v cht tan. Cht tan
trong dung dch thuc bao gm dc cht v cc cht ph, vi cc vai tr nh sau:
- C ht ph n nh (chng oxy ho, chng thu phn...)
- Cht lm tng tan.
- C ht bo qun (chng vi khun, nm mc)
- C ht to h m pH, iu chnh pH (m bo n nh, sinh kh dng
ca thuc, trn h kch ng...)
- Cc cht ng trng (thng dng trong dung dch thuc tim, thuc
nh mt).
Cc dung mi c la chn cho dung dch thuic, tu theo mc ch, tc
dng iu tr v ng dng thuc...
Dc cht v dung mi, c dng pha ch dung dch thuic phi t cc
ch tiu ra theo tiu chun Dc in v l ho tnh, tinh khit, gii hn tp
cht... Dung mi phi khng c c tc dng dc l, khng c hi, khng tng
k vi dc cht v bao gi.

5. Phn loi cht tan, dung mi theo phn cc v kh nng ho tan

phn cc ca dung mi v cht tan, ph thuc vo kiu lin kt ca cc

nguyn t v s sp xp ca cc nhm nguyn t trong phn t.
Lin kt in ho tr hay lin kt d cc (lin kt ion - lng cc) to nn
phn t phn cc.
S c m t cc nhm phn cc nh -OH, -NH2, - SH, -CHO, -COOH, =CO,
trong phn t lm cho cc cht tr nn phn cc.
Loi cht c phn cc tru n g gian gia hai loi phn cc v khng phn
cc, gi l cht bn phn cc.
Qu trn h ho ta n v tng tc tnh in gia dung mi v cht tan:
Qu trn h ho tan xy ra khi lc h t gia cc phn t dung mi vi phn t
hoc ion cht tan, ln hn lc h t gia cc phn t, ion cng loi.
Lc h t hay tng tc tnh in gia dung mi v cht ta n c th bao gm
cc loi :
- Lc h t ion - lng cc (Na+c r vi H 20)
- Lc h t lng cc - lng cc (nitrobenzen - nc)
- Lc h t lng cc - kh lng cc (m ethanol - benzen)
- Lc h t kh lng cc - kh lng cc (paran - hexan)
Cc lc tng tc trn thc y qu trn h ho tan xv ra nhanh.

47
 Nguyn tc c bn xt on kh nng ho tan l cc cht c tnh cht
tng t (v phn cc, cu trc ho hc, nhm ho chc...) th ho tan trong
nhau. V d: Saccharose c nhiu chc - OH d tan trong nc, lu hunh d tan
trong carbon sulfua...
Nh vy, cc cht phn cc tan trong dung mi phn cc, khng tan trong
dung mi khng phn cc v ngc li, vi cht khng phn cc ch tan trong
dung mi khng phn cc.
H ng s' in mi biu th mc phn cc ca mt dung mi, dung mi
phn cc m nh c hng s in mi ln, dung mi cng km phn cc c hng s
in mi cng nh (bng 2 . 1).

Bng 2.1. Hng s in mi v kh nng ho tan ca mt s dung mi

Hng s din mi Kh nng ho tan

Dung mi
(tr s gn ng)

I 80 Nc Mui v c, hu c
50 Cc glycol ng, tanin
30 Ethanol, methanol Du thu du, tinh du
20 Cc aldehyd, ceton, cc alcol bc cao, Nha, tinh du, cc alcaloid,
ether, ester,... cc phenol...
5 Benzen, tetraclorid carbon, ether du Cht bo, parain, cc
ho, du khong vt, du thc vt hydrocarbon...

Vic phi hp cc dung mi, lm thay i hng s" in mi v p hn cc

ca hn hp dung mi, t lm thay i kh nng ho ta n i vi ch t tan, ln
hn nhiu so vi vic dng tng dung mi.
Lin kt hydro (lin kt bng cu hydro) l lin kt gia 2 nguyn t nh
mt nguyn t hydro lm trung gian. S hnh th n h lin k t hydro gia cc cht
vi nc lm tng ho tan ca cc cht trong nc nh i vi cc c h t c ho
chc alcol, amin, amid.

6. tan ca cht tan v nng dung dch

tan ca mt cht trong mt dung mi, mt iu kin n h it , p su t

xc inh, l ty l gia lng cht tan v lng dung mi, ca dung dch bo ho
cht tan trong dung mi cho, khi qu trn h ho ta n t n tr n g th i cn
bng (s phn t ho tan vo dung dch bng s phn t c k t tin h li t dung
dch).
tan ca mt dc cht, c qui c theo lng ti thiu s" m ililit dung
mi cn thit lm tan mt gam dc cht. Theo DVN III, dng cc cch gi
quy c sau y v tan (bng 2 .2 ).

48
 Bng 2.2. Cch gi quy c v tan ca dc cht

Lng dung mi cn thit (ml)

Cch gi ho tan 1 g dc cht

Rt d tan Khng qu 1ml

D tan T 1 n 10ml

Tan c T 10 n 30ml

t tan T 30 n 100ml

Kh tan T 100 n I.OOOml

Rt kh tan (gn nh khng tan) T 1.000 n -lO.OOOml

Thc t khng tan Qu 10.000ml

Chm tan i hi mt thi gian mi tan

Nng ca dung dch l t s' gia lng cht tan v lng dung mi ca
chnh dung dch .
Trong k th u t bo ch thng dng loi nng phn trm khi lng trn
th tch (vit t t l % kl/tt).
Nng phn trm khi lng trn khi lng (vit t t l % kl/kl), c s khc
bit so vi nng % kl/tt, do t trng ca dung mi khc 1. Nng % kl/tt th u n
li cho pha ch v tnh ton liu lng khi s dng, bng cch ong o th tch.

II. DUNG MI CHNH DNG IU CH DUNG DCH THUC

1. Nc - k thut iu ch nc ct v nc kh khong

Nc l mt dung mi phn cc m nh, ho ta n phn ln cc hp cht phn

cc. I vi cc hp cht hu c, kh nng ho tan ca nc km hn alcol.
Trong s' cc dc ch't, nc ho ta n c cc acid, base, cc ng c nhm
phn cc, cc phenol, aldehyd, ceton, amin, acid amin, glycosid, gm, tanin, cc
polypeptid, enzym. Cc cht nha, cht bo, alcaloid base khng tan trong nc.
Nc c acid ho, l mt dung mi tt cho mt s" hp cht cht hu c
nh cc alcaloid base. Nc kim ho ho tan c cc acid, cc cht lng tnh,
cc cht hu c c nhm chc acid nh mt s" saponin.

1.1. K thut iu c h n c ct

Nc thng dng trong bo ch l nc ct, iu ch t nc sinh hot

bng phng php ct. Nc dng iu ch nc ct phi t tiu chun do
Vin V sinh dch t quy nh cho nc dng sinh hot.

49
1.1.1. X l ngun nc trc khi ct nc
V nguyn tc, nc cn phi c lm sch s b, trc khi a vo ni ct
iu ch nc ct. Phng php lm sch ph thuc vo tp cht c trong nc.
cc c s c my ct nc lin tc hin i, ngun nc sinh hot, trc khi dn
vo ni ct, c i qua b phn c cc m ng lc v cc cht nha hp ph trao
i ion, nhm loi cc tp ion, loi Ca^2, Mg+2 gim cng ca nc.
Trong iu kin n gin, vic loi tp trong ngun nc dng iu ch
nc ct c th thc hin nh sau :
Tp cht c hc loi b bng cch lng v lc.
Cc tp cht hu c c ph hy bng kali perm an g an at. Lng kali
perm anganat dng ph thuc vo hm lng cc cht hu c trong nc.
2K M n0 4 + H20 -> 2 KOH + 2M n0 2 + 30
Oxy mi sinh s ph hu cc tp cht hu c.
Thng ngi ta thm kali p erm anganat vo nc cho n khi c m u hng
bn vng. Khuy u, yn nc trong 6 - 12 gi. Sau lc v em ct.
C th loi tr cc tp cht bay hi (amoniac) bng cch un si nc trong
nhng dng c khng np hoc cho nc tc dng vi nhng ho ch t c kh
nng c" nh amomac. Mt trong nhng ho cht thng dng c nh
amoniac l phn chua. Do tc dng ca acid sulfuric (to th n h khi phn chua b
thu phn) vi amoniac, s th u c amoni sulfat khng bay hi.
2KA1(S0 4)2 + 6 NH4OH -> K2S 0 4 + 2A1(0H )3 + 3(NH 4)2SO,
Lng phn chua ph thuc vo lng amoniac v thng dng l 0,5%.
Nu trong nc c cc ion c r , vo cui giai on ct, c th x u t hin acid
hydrocloric do thu phn nhm clorid to th n h t phn chua:
2KA1(S0 4)2 + 6 NaCl -> K 2S 0 4 + 2N a 2S 0 4 + 2 AIC3
AICI3 + 3H20 -> A1(0H )3 + 3HC11
HC1 bay hi lm cho nc ct th u c khng t ch tiu, vi vy, cho thm
mui dinatrihydro phosphat vi lng bng 2/3 lng phn chua, ngn cn phn
ng to acid hydrocloric theo c ch sau y :
2 AICI3 + 3Na 2H P 0 4 -> A12(H P 0 4)3 + 3NaCl
Ngoi cc tp cht c hc v tp cht bay hi, nc cn cha cc tp ch t v
c. Thng hay gp n h t l calci hydrocarbonat v m agnesi hydrocarbonat. Nc
cha mt lng ln mui calci v m agnesi goi l nc cng. cng ca nc ph
thuc vo s miligam ng lng ca cc ion calci, m agnesi c trong mt lt nc:
- Nc r t mm cha 0 - 1,5 mg ng lon lng Ca2+ v Mg+ trong 1 lt.
- Nc mm cha 1,5 - 3 mg ng lng ion Ca2+ v Mg-+ trong 1 lt.
- Nc trung bnh cha 3 - 6 mg ng lng ion Ca2+ v Mg2+ trong 1 lt.
- Nc cng cha 6 - 10 mg ng lng ion Ca2+ v Mg2t trong 1 lt.

50
 Nu iu ch nc ct t nc cng, trong qu trn h un nng, di tc dng
ca nhit, calci hydrocarbonat v magnesi hydrocarbonat s cho mui carbonat
tng ng:

Ca(HC03)2 -> C 02 + H20 + CaC03 i

Mg(HC03) -> C 02 + H20 + MgCOs i

Cc mui carbonat ny ng th n h cn y ni un lm cho nc lu si v

cc lp cn ny c dn nhit km ( dn nhit ca cc lp cn carbonat ch l
2 trong khi dn nhit ca st l 60, ca ng l 100). Khi c mt lpcn dy
lm m th lng nhin liu phi dng tng ln t 15 n 40%.
Trc khi cho nc vo ni un, phi s b lm mm nc nu nc c
cng cao. lm mm nc, ngi ta thm vo nc mt lng calci hydroxyd v
n a tri carbonat c tnh sn, tu theo cng ca nc.
Calci hydroxyd loi cng tm thi ca nc, bng cch chuyn calci
hydrocarbonat v magnesi hydrocarbonat thnh carbonat kt ta :

C a(H C 0 3)2 + Ca(OH )2 -> 2 HzO + 2C aC 03 1

M g(H C03) + Ca(OH )2 -* 2H20 + C aC 0 3 i + MgCOg i

N atri carbonat loi cng vnh cu ca nc bng cch chuyn cc mui

magnesi v calci tan trong nc th n h carbonat khng tan.

CaCl 2 + N a 2C 0 3 - C aC 0 3 i + 2 NaCl

Sau khi thm cc ho cht v khuy, phi yn nc trong mt thi gian

lng ng ta, gn hoc lc ly phn nc trong em ct.
C th dng nha trao i ion lm mm nc, nh nu trong m y ct
nc lin tc. C ch ca phng php ny c trn h by trong phn iu ch
nc kh khong.
trnh phi x l cng ca nc, nn dng nc ma iu ch nc ct.

1.1.2. Thit b iu ch nc ct v k thut vn hnh

Ni ct thng gm 3 b phn :
- Ni bc hi (ni un), trong nc c un si v ho hi. B phn ny
thng lm bng ng trng thic, thp khng g... thng c hnh tr.
- B phn ngng t c ng sinh hn, lm theo nhiu kiu khc nhau: ng
xon rut g, ng di hoc hnh a. C khi ngi ta phi hp cc kiu trn
tng din tch lm lnh.
- Bnh hng nc ct bng thu tinh hoc thp khng g.

51
 Ni ct nc c ch to theo nhiu kiu khc nhau c th l nhng ni
ct nc hot ng lin te hoc khng Mn tc.
Ni ct nc thng thng :
Tu theo v tr ca b phn ngng t i vi V tr ca b phn bc hi, ngi
ta chia ra 3 loi ni ct nc.
- Kiu ni c b phn ngng t cnh b phn bc hi (hnh 2.2)
- Kiu ni c b phn ngng t pha trn b phn bc hi (hnh 2.3)
- Kiu ni c b phn ngng t pha i b phn bc hi (hnh 2.4)
Vi loi ni ct hot ng khng lin tc, thng thu c nc ct t nhng
phn nc ring bit. Mun nc vo b phn bc hi, phi tm ngng qu
trn h ct. Thng ch c nc n 2/3 ung tch ni, khi si, nc khng
bn sang b phn ngng t. lm sch ng dn hi nc v ng sinh hn, trc
khi hng nc ct, phi cho hi nc nng i qua trong 5 - 10 pht khng lm
lnh. Sau , cho nc lnh vo b phn ngng t v hng nc ct. Phn nc
ct u thng cha nhng tp cht bay hi nn b i vi lt. Khi qu trnh ct
kt thc, nc cn li trong ni khng c t hn 1/4 so vi lng nc ban u.

Hnh 2.2. S kiu ni ct c b phn ngng t cnh b phn bc hi

1, B phn bc hi 3. B phn t nng
2. B phn nguhg lnh; 4. Knh nc; 5. Van chn nuc

52
 Hnh 2.3. S kiu ni ct c b phn Hnh 2.4. Sd kiu ni ct c b phn
ngng t trn b phn bc hi ngng t di b phn bc hi
1. B phn t nng 1. B phn t nng
2. ng dn hi nc 2. B phn lm lnh
3. B phn ngng t 3. ng dn nc ct

cc ni ct lin tc, nc lm lnh b phn ngng t, sau khi nng ln

do tip xc vi hi nc nng trong ng sinh hn, c t ng tip sang b phn
bic hi. Phng php ct lin tc cho hiu sut cao hn v tn t nhit lng hn.
Cn ch nc b phn ngng t (nc lm lnh) c t ng tip th n g vo
b phn bc hi nn nc lm lnh cng cn phi c x l trc.
Ni ct nc kp:

Hnh 2.5. S cu to ni ct nc kp

Ni ct nc kp l thit b phc tp hn ni ct thng. T hit b gm 2 ni

hi bng thp khng g. Nc kh khong c i qua bnh ngng t n 2 ni hi
c mc nc c nh. Ni s 1 c un nng bng mt ng xon, dn hi nc
nng vi p sut cao (khong 2,5 atm). Ni ny c gi p su t khong 1,5 atm ,

53
do nc s si 110c. Hi nc do ni 2 cung cp s ngng t trong ng xon
ca bnh ngng t 3 v truyn nhit cho nc dng ct. Nc ngng t y,
tip tc ngui trong bnh lm lnh 4 v hp vi hi nc ca ni 1 ngng t trong
ng xon ca ni 2 .
My ny c th dng iu ch nc ct 2 ln. Mun vy ch cn cung cp
nc ct ln 1 cho ni s 2 nh h thng vi 3 chc, t sau ni hi ny. My ct
kp c hiu sut nhit cao hn ni ct thng thng (1,5 - 1,7 ln).
My ct nc nhit nn:
My ct nc nhit nn vn hnh theo nguyn tc khc vi cc m y ct
thng thng. c im chnh ca my :
- Ct p su t hi thp hn p su t thng.
- Sau khi b nn, s ngng t ca hi nc xy ra cng n h it ca nc
ho hi, nhng p su t hi cao hn p su t bnh thng, khng cn nc lm
lnh (do truyn nhit cho ngun nc cn ho hi ni 1)
- My c un nng bng in v c cch nhit hon ton trnh hao
h t nhit lng. Hiu su t nhit ca my ny r t cao (khong 30W cho 1 lt nc
ct i vi my cng su t 150 lt/gi).

Hnh 2.6. S my ct nc nhit nn

1. Ni hi 5 v 6. in tr
2. My nn 7. B phn cp nc c mc n nh
3. Bnh ngng t 8. Van iu chnh
4. Bnh trao i ion

Cn tin h nh ct nc trong iu kin v sinh sch s. Bnh cha nc r t

cn y kn, tr n h hin tng ho tan kh carbonic trong khng kh vo nc
nh hng n tan ca mt s' dc cht.

54
 c n kim tra nh k tinh khit ca nc ct theo quy nh cua Dc
in. m bo v khun nc ct cn c dng ngay sau khi ct hoc lun
c bo qun 80c.

1.2. K thut iu c h nc k h khong

Nc kh khong l nc tin h khit, c loi sch cc tp cht ion trong

nc, bng phng php dng cc cht hp ph trao i ion.
c im ca nc kh khong, khc vi nc ct l c tin h k hit ho hc
cao, hm lng cc tp cht ion thp (nht l cc ion kim loi) nhng khng v
khun. Nc kh khong c ghi vo chuyn lun ca mt s" Dc in.
Hin nay, nc kh khong c dng ph bin, thay nc ct, iu ch mt s
dng thuc trong k th u t bo ch nh cc thuc nc dng ngoi, thuc ung.
Cc cht hp ph trao i ion c gi l cc ionit. Ionit v c t c s
dng v dung lng trao i ion thp. Ionit v c thin nhin nh cc Bentonit,
Zeolit... Ionit v c tng hp nh aluminosilic gn vi kim loi kim th c tn gi
Perm utit. Cc ionit hu c thng c s dng rng r i v c dung lng trao i
ion ln, c tng hp bng cc phng php ngng t, tr n g hp nh W olfatit,
Amberlit, Dower...
Cu to ca cc ionit:
Bao gm 2 phn : Khung khng tan trong nc v cc nhm hot ng. Phn
khung khng tan c c tnh, trng n trong nc, to xp, tn g b m t tip
xc ca cc h t nha ionit vi nc, cc nhm hot ng c gn trn b m t ca
khung c kh nng trao i cc ion.
Dung lng trao i ion ph thuc vo s" nhm hot ng v xp trng
n ca cc ionit.
Cc ionit c kh nng hp ph, trao i cc cation trong nc gi l cationit,
hp ph trao i cc anion gi l cc anionit.
Cc cationit l cc acid m nh (vi nhm hot ng l - S 0 3H) hoc acid yu
(vi nhm - COOH, - OH phenol). Cc anionit l cc base m nh (vi nhm hot
ng amoni bc 4) hoc base yu (vi cc nhm base amin bc thp).
C ch lm sch cc tp cht ion trong nc, ca qu trnh iu ch nc
kh khong, l s hp ph trao i ion trn b m t r n - lng, gia cc h t ionit
v ngun nc. Qu trn h trao i ion thng din ra qua hai giai on: Cc ion
trong dung dch khuch tn, tp tru n g mt s" ln ion ln tr n b m t cht trao
i ion, do lc h t vi nhm phn cc trn b m t, tip sau l qu trn h trao
i cc ion.
Nguyn tc ca phng php iu ch nc kh khong l cho nc i qua
ct cha cationit v anionit, gi li cc lon.
Khi i qua cc ct cationit di dng acid (dng hot ng) cc cation b hp
ph v trao i vi H+ vo dung dch theo cc qu trnh sau:

55
 RH++ Na+ + c r - R 'N a+ + H+ + c r
2 RH+ + Ca2+ + 2HCO_3 -> R-2Ca24 + 2H+ + 2H C 0'3
Khi tip tc i qua ct anionit di dng kim (dng hot ng) cc anion b
hp ph v trao i ion OH vo dung dch, to thnh nc tinh k hit v tru n g
tnh.
R+OH' + H+ + c r -* R+c r + H,0
2R+O H '+ 2H++ s o r -> R 2+S O |' + 2H 20
Cc ct ionit c th c lp t, b- tr kiu thng thng l ct cationit
trc ct anionit, kiu b tr ngc l ct anionit t trc. Ngoi ra cn c kiu
b tr hn hp, trong 1 ct cha c 2 loi cationit v anionit c trn u. T l
cc cationit v anionic tu thuc vo dung lng trao i ion ca 2 loi m
bo loi sch tp ion.
Cc mui carbonat v hydrocarbonat to th n h s b phn hu trong mi
trng acid. Kh carbonit c loi tr bng cch un si nc.
Khi cationit v anionit khng cn kh nng trao i ion, ngi ta hon
nguyn chng, bng cch ra nha cationit vi dung dch acid HC1 3 - 6 % v ra
nha anionit vi dung dch NaOH 3 - 4%. Thc cht, y l qu trn h phn hp
ph, tr cc ionit v dng hot ng, vi phng trn h trao i ion nh sau :

R~Na+ + H+ + c r -> R"H + Na+ + C1

R +C r + N a++ OHT -> R +OH- + N a++ c r
Sau ra cc cht trao i ion ti sinh vi nc ct, cho n khi ht vt
cc ion. Vic hon nguyn ionit. c th thc hin bng cch ngm ra ionit trong
thng chu, vi dung dch ra (dung dch phn hp ph trao i ion) hoc dung
dch ra chy chm qua ct ionit.
Hn hp nha cationit v anionit c tch ring tng loi trong nc
em hon nguyn nh s khc nhau v t trng.
kim tra cht lng kh khong, u ng ra ca nc kh khong c
lp mt ng h o in tr. Nc kh khong tt, c in tr tr n 1 4 triu
Ohm.cm, nh hn 1 triu Ohm.cm l nc c cht lng km.
Qu trn h iu ch nc tinh khit bng cht trao i ion c u im l
khng cn ngun nhit, thun tin v d thc hin trong cc hiu thuc v phng
bo ch. Nc kh khong c th t c tinh khit ho hc cao. N hng ngc
li, v m t sinh hc, khng th coi l t yu cu v cc cht trao i ion khng c
kh nng hp ph cc cht gy st (ch nhit t) v cc vi khun. Ngoi ra. ngi
ta cn thy, khi bc hi nc kh khong, i lc th u c mt cn en do nc
ho tan mt phn r t nh th nh phn ca nha ionit, chng t ionit c th th
tp vo nc. y cng l l do khng dng nc kh khong pha thuc tim .
Ngoi phng php kh khong nc bng cht trao i ion, ngi ta cn
dng phng php siu lc, phng php thm th u ngc, nhng cc phng
php ny t c cng dng thc t trong Ngnh dc.

56
 2. Cc dung mi phn cc thn nc
Cc alcol, ni chung, l nhng dung mi phn cc, do s c m t ca cc
nhm hydroxyl trong phn t ca chng. Alcol bc n h t l nhng ch t tan trong
nc v l dung mi tt cho cc cht phn cc m nh.
Mch hydrocarbon trong dy ng ng cng tng, tnh phn cc v kh nng
trn ln vi nc ca alcol cng gim. Cc alcol bc cao, c nhiu nhm hydroxyl, c
tnh phn cc m nh hn cc alcol tng ng, ch c mt nhm hydroxyl.

2.1. E th a n o l

Trong cc alcol, ethanol c s dng rng ri n h t trong ngnh dc. N c

th ho tan cc acid, cc kim hu c, cc alcaloid v mui ca chng, mt s
glycosid, nha, tinh du, mt s lipid mu, ... ethanol khng ho tan pectin, gm,
protid, enzym...
Ethanol to ho tan b t c t l no vi nc v glycerin.
Khi trn ln ethanol vi nc, s c hin tng to nhit v th tch dung
dch th u c nh hn tng th tch ca ethanol v nc tham gia to dung dch.
Nhng bin i ny l do hin tng hy d rat ho cc phn t ethanol, to
th n h phc hp phn t c cng thc nh sau :

R R

J_ J
H H

i vi mt s' dc cht, hn hp ethanol - nc c kh nng ho ta n cao

hn so vi cc th n h phn ethanol v nc ring r.
E thanol c u im l c tc dng st khun. Mt s" dc cht vng bn
trong ethanol hn trong nc. Ethanol l dung mi c kh nng lm tn g n
nh v sinh kh dng thuc ucmg. Tuy nhin, ethanol cng c nhc im l
khng hon ton tr v m t dc l, d bay hi, d chy, lm ng vn album in,
cc enzym v d b oxy ho.

2.2. G ly ce rin

s L sn phm th u c khi x phng ho cht bo, glycerin l mt ch t lng

khng mu, snh, v ngt nng, c phn ng tru n g tnh.
Glycerin ho tan vi ethanol v nc bt c t l no, khng ho tan clorobrm,
ether, du m.
Glycerin ho tan mt s" mui acid hu c v v c, ho tan alcaloid v mui
ca chng, cc tam n, ng...
Glycerin khan nc r t d h t m v thng gy kch ng da, nim mc. V
vy, trong bo ch ch dng glycerin dc dng c t trng 1,225 - 1,235 cha 3%
nc, khng gy kch ng. nng 25%, glycerin c tc dng s t khun.
Glycerin ch yu thng c dng trong cc dng thuc dng ngoi.

57
2.3. G ly c o l v c c dn ch t

Butylen glycol v propylen glycol : l nhng dung mi hu c khan nc,

trn ln vi nc, ho tan c nhiu cht t tan hoc khng ta n trong nc nh:
Cc phm mu, tinh du, nha ... Glycol v cc dn cht l dung mi tt, m
tng n nh cho dc cht d b thu phn nh cloramphenicol, acetyl cholin...

3. Cc dung mi khng phn cc thn du

3.1. Du thc vt

L hn hp cc glycerid ca acid bo bc cao. Thng dng du lc, du

hng dng. Cc du thc vt khng ta n trong nc, t ho ta n trong cn, d ho
tan trong cloroorm, ether v eth er du ho. D u thc vt ho ta n c mt s
dc cht hu c nh salol, long no, m enthol, tin h du, cc a lc a lo id base,
vitam in A, D, E.

3.2. C lorotorm

Trn ln c vi a s" cc dung mi hu c. L dung mi tt cho cht bo,

du m, tinh du, cc alcaloid base, ... dung mi ny t c dng trong dung dch
thuc, thng dng lm dung mi chit xut.

II. K THUT CHUNG IU CH DUNG DCH THUC

K th u t iu ch dung dch thuc, ph thuc vo tn h cht l ho ca cc

th n h phn v mc ch iu tr.
Nhn chung, k th u t iu ch bao gm cc giai on chnh sau y:
1. Cn hoc ong dc cht v dung mi
2. Ho tan
3. Lc
4. Hon chnh ng gi th n h phm

1. Cn, ong dc ch't v dung mi

Cn, ong chnh xc, m bo hm lng thuc theo quy nh ca Dc

in. Trong phng bo ch, khi pha ch cc dung dch c nng % khi lng
trn th tch, thng dng h thng buret. Phng php ny s dng cc dung
dch gc, thng c nng cao hn dung dch cn pha 5 - 10 ln, c pha
sn, lm tng hiu sut v gim sai s" cn, th u n tin cho vic pha ch theo n.

2. Ho tan v cc yu t nh hng

2.1. Q u trnh ho tan

Qu trn h ho tan xy ra theo nguyn l n h it ng hc, trong iu kin khi
bin thin th ng p (AG) nh hn khng, theo phng trn h n hit ng hc:

58
 AG = AH - TAS
Trong , AH l nhit to ra hay thu vo khi qu trn h xy ra (nhit ho
tan), AS l entropy - biu th mc khng tr t t ca h, T l nhit .
N hit ho tan (AH), c m quan h vi nhit solvat ho (AHsolv) v nng
lng ph v cu trc tinh th ca cht rn (E), theo phng trn h sau y :
AH = E + AHsolv
Trong , lun lun E > 0 v AHsolv < 0.
Trong hu ht cc trng hp, E > AHsolv, do vy, AH > 0, qu trn h ho tan
khi AH > 0 l qu trn h thu nhit. Trong mt s" trng hp, AHsolv > E, do
AH < 0, qu trn h xy ra khi to nhit. Nguyn l nhit ng hc nu trn, l
c s xt on nh hng ca nhit n tan, cng nh tc ho tan.

2.2. C c yu t nh hng n tan v t c h o tan dc ch t

2.2.1. tan ca cht kh trong cht lng

Theo nh lu t Henry tan ca cht kh t l th u n vi p su t kh trn b

m t dung dch, biu th bng phng trn h sau:
w = kp
Trong w l cht kh ho tan trong 1 n v th tch cht lng, k l hng s
t l. tan ca cht kh trong dung dch s gim khi tn g nhit . Vn dng
trong ngnh dc, nhiu chuyn lun dc in yu cu s dng nc ct va
mi un si loi phn ln lng kh ho tan trong nc ct (nh C 0 2, 0 2...)
nhm mc ch tr n h nh hng ca cc kh ny n n nh ca dc cht
trong dung dch thuc.

2.2.2. tan ca cht rn trong cht lng

Cc yu tc nh hng n tan
ca cc dc cht r n trong dung dch c
ngha quan trng trong pha ch thuc,
ln lt c kho s t nh sau :

nh hng ca nhit :
Nh nu phn trn, i vi qu
trn h ho tan dc cht c s th u nhit
(AH > 0) theo nguyn tc Le Chatelier,
vic tng nhit (cung cp nhit) s
thc y qu trn h ho tan, lm tng
tan ca dc cht. Ngc li khi dc
cht ho tan to nhit (AH < 0), vic tng
nhit s lm gim tan ca dc
cht.
mt s cht trong nc theo nhit

59
 Tuy nhin, i vi phn t kt tinh ngm nc, trong qu trn h ho tan,
nhit c th nh hng n tan theo chiu hng ngc nhau, do c s m t
nc kt tinh chuyn sang dng khan.
V d: Na2S 0 4.10H20 , c tan tng khi nhit n di C2,5c ( th
hnh 2.7), trn nhit ny tan s gim khi tng nhit . Nguyn nhn l
N a2S 0 4.10H20 ho tan th u nhit (endothermic), cn N a2S 0 4 ho ta n to nhit
(exothermic).
nh hng ca bn cht v c im cu trc phn t ca cht tan v dung mi:
Bn cht v c im cu trc phn t ca cht ta n v dung mi l nhng
yu t' ho hc ni ti nh hng n tan. Yu t ny c phn tch trong
phn c tnh phn cc ca dung mi v cht tan. Cu trc p hn t, cng nh cc
nhm chc c trong phn t cht tan v dung mi quyt nh c tn h phn cc.
V d in hnh nh phenol khi c thm nhm OH tng tan trong nc gp 100
ln so vi benzen. Cc nhm chc th n nc OH, NH2, SH,... c trong phn t
cht tan, s lm tng tan ca cc cht ny trong nc, do tn g phn cc.
Vic chuyn mt s' dc cht dng acid yu sang dng mui, s lm tng
tan, do cc mui ny c phn ly ln hn. Trong mt s trng hp cn lm
gim tan bng cch chuyn dc cht sang dng ester ho, nhm hn ch s
phn hu v v ng nh cloramphenicol chuyn sang dng cloramphenicol
palm itat, erythrom ycin chuyn sang dng erythrom ycin propionat.
A nh hng ca c tnh kt tinh, hin tng a hnh v s solvat ho n tan:
Mt dc cht c th kt tinh di nhiu dng tin h th khc nhau, tu theo
iu kin kt tinh. Cc dng kt tinh khc nhau, s c cu trc tin h th bn vng
mc khc nhau, t c tan khc nhau. V d, am picilin k h an c tan
ln hn ampicilin trihydrat.
Dng kt tinh c cu trc tinh th bn vng nn thng kh ta n hn dng
v nh hnh. Novobiocin c dng v nh hnh d ta n hn dng k t tin h 10 ln.
A n h hng ca kch thc tiu p hn dc cht n tan:
tan ca dc cht tng ln khi kch thc tiu phn gim, do nng lng
t do trn b m t tip xc tng ln, biu th trong phng trn h sau y:

s 2EM
lg ------ = ------- _ _
s 0 2,303 RTpr

Trong , s l tan ca tiu phn c nghin mn, c ng knh r, S0 l

tan ca dc cht c kch thc tiu phn ban u, E l nng lng t do trn
b m t tip xc, M l khi lng phn t, p l t trng cht rn, R l hng s kh
T l nhit nhit ng hc. Nh vy, vic nghin mn dc cht r n s lm tn g
tan mt mc no .

60
 n h hng ca p H dung dch n tan:
i vi cc cht in ly yu, nh hng ca pH dung dch n ta n c
xem xt trong 3 trng hp khc b i t : Cht tan l cc acid yu, base yu v lng
tn h (mang c 2 tnh acid yu v base yu):
- Vi acid yu: Nh cc barbituric, phenylbutazon, nitrouratoin..., mi
quan h gia tan s vi pH v pKa biu th bng phng trnh:

l o g ^ ^ = pH-pKa

(S0 l tan ca dc cht dng khng phn ly).

- Vi cc base yu: Nh cc alcaloid, clopromazin..., c phng trn h tng
t, vi biu thc phn s o ngc khi thay pKb bng pKa.

l o g - ^ - = p H -p K a

Nh vy, khi pH ca dung dch tng (kim ho dung mi) s lm tn g tan

ca acid yu v gim tan ca cc base yu, trng hp ngc li, khi gim pH
dung dch (acid ho dung mi).
- Vi mt s" cht lng tnh: Nh cc acid amin, cc sulphonam id,
oxytetracyclin..., cc cht ny c t n h t 2 hng s' in ly.
Kal K*
HAH+ - HA* A'
H+
(Cation) (Phn t trung ho (Amion)
im ng in)
pH nh hn im ng in, c phng trn h biu th mi quan h gia
tan pKa v pH.

l o g - ^ - = p H -p K a ,
^ 0
pH ln hn im ng in, phng trn h biu th m quan h gia
tan pKa v pH s l :

lo g ^ ^ - = pH-pKa 2
0
Nh vy, tn g pH di im ng in s lm gim ta n ca cht tan
lng tnh v trn im ng in s lm tng tan.
th trong hnh 2.8 m inh ha 3 trng hp nu trn.

61
 Hnh 2.8. th biu din logarit tan ca mt s cht theo s thay i pH

nh hng ca cc ion cng tn:

Trong dung dch, cc ion cng tn A+ hoc B", vi cc ion ca cht ta n tham
gia vo cn bng phn li ca cht tan AB.
AB (rn ) AB (d u n g dch) =g= A+ + B
Khi c m t cc ion cng tn, nng cc ion bn phi ca phng trn h
tng ln, y qu trn h ho tan i theo chiu nghch, lp li cn bng p hn ly,
do lm gim tan.
nh hng ca cc cht in ly:
S c m t ca cht in ly lm gim hot ion, lm gim phn li ca
cc cht tan, t lm gim ho tan ca cc cht.
Nh vy, ho tan nhanh, cn ho tan theo th t, cc cht km ta n c
ho tan trc. i vi cc cht in gii cn pha long nng khi phi hp vi
dung dch cc cht km tan, tr n h nh hng ca cc ion c th lm kt t a
cc cht ny.
nh hng ca cc cht to phc hoc dn cht v cc cht din hot n
tan c xem xt trong phn cc phng php ho tan c bit.
2.2.3. Tc ho tan
Tc ho tan ca dc cht c biu th theo phng trnh Noyes - Withney:

62
 = K.A(Cs-Ct)
dt
Trong :
K : Hng s tc ho tan
A : L din tch b m t tip xc ca dc cht vi dung mi
Cs : L nng bo ho ca dc cht
C t : L nng dc cht ti thi im t.

Nu thay K = th tc ho tan c biu thi theo phng trn h

h
dC D.A /_ _ V

= (C s -Q )
dt h 7
T ro n g : D: L h s k h u c h t n c a dc c h t tro n g d u n g m i
h: L b dy lp k h u c h t n .
Cc yu t' nh hng ti tc ho tan c th c xem xt trn c s tc
ng ca chng n cc i lng trong phng trn h biu th tc ho tan.
n h hng ca nhit n tc tan:
Tr mt s" t trng hp, cht c qu trn h ho tan to nhit, vic tng
nhit s lm gim tan, t gim tc ho tan, phn ln cc cht c
tan v tc tan tn g khi tng nhit , do h s" khuch tn ca cht tan trong
dung mi tng cao, nht ca dung mi gim.
V d: Cafein t tan trong nc nhit thng nhng d tan n hit
cao. i vi cc dung mi c nht cao (glycerin, propylen glycol, ...), ho tan
nhanh, cn un nng nh khi ho tan n a tri borat trong glycerin, cloramphenicol
5% trong propylen glycol. n a tri benzoat trong siro n...

Bng 2.3. H s khuch tn ca mt s dc cht

H s khuch tn
Dc cht
20c 70c
Kali clorid 1,71 4,98
Natri clorid 1,34 3,88
Kali sulat 1,05 3,04
Natri sulfat 0,89 2,58
Magnesi sultat 0,46 1,32
Acid citric 0,57 1,65
Acid tartric 0,62 1,81
Saccharose 0,37 1,07
Albumin 0,0088 0,0255

63
 N ghin nh cc dc cht:
Lm tng nhanh tc ho tan do
lm tng din tch b m t tip xc ca
cht tan vi dung mi.
Khuy trn trong qu trnh ho tan:
Lm tng tc ho tan, do cu
trc cc lp khuch tn b ph v, a
lp dung mi mi vo gn b m t cht
tan, ni c lp dung dch bo ho, do
lm tng s chnh lch nng , b dy
lp khuch tn tr ln v cng nh. Kt
qu tc ng vo hai i lng ny lm
tn g n hanh tc ho tan.
Cn lu khi ho tan cc tiu phn
cht keo: c n yn cho cc cht keo Hjnh 2 .9 . S qu trnh ho tan t trn
h t nc trng n hon ton, tr n h xung (per descensum)
khuy trn, lm keo dnh cc tiu phn,
lm gim din tch tip xc ca cht tan vi dung mi. Trong trng hp ny cn
p dng phng php ho tan t trn xung (per descensum ) hay cn gi l
phng php ho tan quay vng.
Dc cht c rc ln m t thong ca dung mi hoc cho vo m t t i vi
treo ngp trong b m t dung mi. Do tip xc vi lp dung mi b m t, dc
cht s tan v to th n h mt lp dung dch bo ho. Lp dung dch ny c t trng
ln nn chuyn ng xung y bnh, y lp dung mi mi c t trng nh ln
b m t, tip tc ho tan mt lng cht tan mi (hnh 2.9).
Phng php ny thng c s dng ho tan cc ch t bc keo hoc
iu ch siro ng n.

2.3. C c ph ng p h p h o tan c b i t

D anh t tr ta n hoc lm cho ta n (solubilisation) c dng ch qu trn h

phn tn cc phn t ca cht kh tan hoc t ta n trong m t dung mi, nh s
tru n g gian ca nhng cht gi l cht lm tan (solubilisant). ho ta n cc ch t
kh tan, c th dng cc phng php ho tan c bit nh to dn ch t d tan ,
dng hn hp cc dung mi, dng cc cht tru n g gian th n nc, dng ch t din
hot.

2.3.1. Phng php to dn cht d tan

i vi mt s' cht kh ta n trong dung mi, c th s dng cht c k h nng

to th n h dn cht d tan vi dc cht. Dn cht ny cn gi c tc dung dc
l ca dc cht ban u, cht tr tan c trong dung dch phi khng em li
nhng tc dng b t li cho dung dch dc cht. in h nh loi ny l dung dch

64
lugol (dung dch iod 1% theo DVN III, c th n h phn iod 1 g, kali iodid 2 g, nc
va u 100 ml). Trong , KI c vai tr to vi I2 (cht r t kh ta n trong nc
ta n 1:2000) th n h dn cht KI3) r t d tan trong nc.
I2 + KI -> KI3
Tc ho tan c quyt nh bi tc phn ng to ra KI3. Nng KI
cng m c, tc phn ng cng nhanh. Do , d dng ho tan I2, ch cn
lng nc ti thiu to dung dch KI bo ho (ng lng cht tan). Khng c
dng nhiu nc trong giai on ny, lm qu trn h ho tan v cng chm, do
gim tic to cht KI3 d tan. Khi I2 chuyn th n h KI3 v ho ta n ht mi
thm nc pha long ti th tch.
Tng t, ho tan thy ngn II iodid trong nc, KI kt hp vi H gl2 to
phc kali tetraiodom ercuriat.
H gl2 + Ki - K2[HgIJ

2.3.2. Phng php ho tan dng hn hp dung mi

Phng php ho tan ny bao gm vic s dng mt hn hp nc v nhng
dung mi th n nc khc (ethanol, glycerin, propylen glycol,...) lm cho hn hp
dung mi c phn cc gn vi phn cc ca dc cht kh ta n trong nc, t
ho tan dc cht d dng.
Cc dung mi thng dng l :
- Cc monoalcol nh ethanol, isopropanol, alcol benzylic...
- Cc polyalcol nh glycerin, propylen glycol, butylen glycol, polyethylen
glycol...
- Cc dn cht nh am in nh ethylendiam in, diethylam inoethanol...
Trong thc h n h bo ch, ngi ta thng dng cc hn hp nc - alcol
ho tan cambr, hn hp glycerin - alcol - nc ho ta n mt s' alcaloid,
glycosid; v d: dung dch digitatin 0,1% c th n h phn dung mi l ethanol,
glycerin, nc; dung dch bromobrm *c th n h phn bromoorm - glycerin -
ethanol, t l 1 : 3 : 6.
Mt s' dung dch s dng hn hp dung mi, ngoi vai tr lm tng tan, cn
tng n nh v sinh kh dng ca thuc c ghi trong Dc in Anh nh:
- Dung dch phenobarbital 0,3% (hn hp dung mi ethanol - glycerin - nc).
- Dung dch paracetamol 2,4% (hn hp dung mi ethanol - propylen glycol -
nc).

2.3.3. Phng php ho tan dng cc cht trung gian thn nc

C th s dng mt s cht hu c th n nc ho ta n mt s cht kh

tan. Nhng cht trung gian ho tan ny thng l nhng cht th n nc. P hn t
ca chng m ang nhiu nhm -COOH, -OH, nhm am in, sulfat..., l cc nhm
phn cc, phn cn li khng phn cc l nhng gc hydrocarbon m ch th n g

65
hoc mch vng. Trong thc h nh bo ch, thng dng acid hu c nh a c id
lactic, acid tartric, n a tri salicylat, antipyrin, uretan, sorbitol, glucose, m anitol...
Vai tr trung gian ho tan ca cc cht ny l do, mt m t chng c phn
hu c c i lc vi phn s nc ca cht kh tan, m t khc chng c nhng
nhm chc th n nc, c i lc i vi phn t nc. Tng tc tnh in ca cc
phn t cht trung gian ho tan vi c hai loi phn t cht ta n v dung mi,
phn tn phn t cc cht t tan vo dung mi nhiu hn, lm tng tan.
Trong bo ch, t lu ngi ta bit dng n a tri benzoat ho ta n cafein,
anestezin, dng acid citric ho tan calci glycerophosphat, dng an tip y rin hoc
u retan tng tan ca quinin.... Ngi ta cng n h n th y hin tng trung
gian ho tan trong thin nhin. Aglycon ca cc glucosid thng kh ta n trong
nc nhng cc glucosid tng ng, trong aglycon c k t hp vi cc ng
(manitol, sorbitol, ructose, glucose...) l cc cht d tan.
Bng phng php ny, c th thu c kt qu ho ta n tt, nhng i khi
cn phi s dng cc cht trung gian ho tan vi t l ln, i khi ln hn c
lng cht cn ho tan.

2.3.4. Phng php ho tan dng cc cht din hot (cht hot ng b mt)
Trong k th u t bo ch hin i, ngi ta cn hay dng cc ch t din hot
lm cht trung gian ho tan. C ht din hot l nhng cht khi ta n trong dung
mi, c kh nng lm gim sc cng b m t phn cch pha . c im cu to ca
cc cht din hot l phn t ca chng gm 2 phn: phn th n nc v phn
th n du. 0 nng thp, cc cht din hot c th phn tn di dng phn t
trong nc to th n h cc dung dch tht. Nu nng tn g ln n mt gii
h n no , cc phn t cht din hot tp hp th n h cc micell v dung dch tr
th n h dung dch keo. Nng ny c gi l nng micell ti hn. Trong
micell, cc phn t cht din hot c th c sp xp th n h hnh cu, th n h cc
lp song song hoc th n h hnh tr. Cc phn t hoc tiu phn cht ta n c
phn tn, hp th vo trong cu trc ca cc micell hoc vo gia cc lp micell.
Cc phn t cht tan c gi li trong micell khng tham gia vo cn bng ca
dung dch trng thi bo ha, do nng cht tan trong dung dch tn g ln.
thm nhp ca cc tiu phn dc cht vo trong micell cht din hot ph
thuc vo tnh phn cc ca cc phn t dc cht.
Nh vy, iu kin cht din hot c tc dng lm tn g ta n ca mt
cht khc l cn c dng vi lng ln, to nng ln hn nng micell
ti hn. C ch lm tng tan ca cht din hot l hp th cht ta n vo micell.
Dung dch thu c ngoi cu trc l dung dch th t cn l dung dch keo.
Trong thc hnh bo ch, cc Tvveen l nhng cht din hot hay c dng
lm cht trung gian ho tan. Dung dch Tween 20 (5%) trong nc c th lm tan
mt s cht kh tan hoc khng tan trong nc. Tween c th ho ta n trong nc
cc cht st khun dn cht ca phenol, cc hormon steroid, cc vitam in tan
trong du, cc khng sinh (cloramphenicol, griseofulvin...), cc sulam id, cc
barbituric... Tween cn c dng ho tan tinh du trong nc iu ch nc
thm. Vi mt lng Tween gp 5 ln lng tinh du, c th iu ch dung dch

66
tin h du 1 - 2% trong nc, trong sut v n nh lu di. iu cn ch l trong
cc dung dch thuc ung, khng nn dng qu 3% Tween v ch phm c v kh
chu. M t khc, cht din hot cng c th lm gim hiu lc ca mt s dc
ch t (khng sinh v cht st khun).

3. Lc dung dch

Lc l qu trn h loi tiu phn cht rn khng tan trong dung dch, bng
cch cho dung dch i qua vt liu lc th u uc dung dch trong.

3.1. Q u trnh l c

Qu trn h lc xy ra c l do kh nng ca cc vt liu lc, thng l

nhng m ng chn c l nh, cho php cht lng i qua v gi li cc tiu phn
cht rn.
Ngi ta thng so snh qu
trn h lc vi mt qu trn h c hc
khc l qu trn h ry. Nhng tiu
phn c kch thc ln hn kch
thc l xp ca vt liu lc b gi li
trn m ng lc (hnh 2.10a). Tuy
nhin, nhiu trng hp tm vt liu a b c
lc c kh nng gi li c nhng tiu
phn c kch thc nh hn kch Hnh 2.10: S lc cc tiu phn
thc l xp ca m ng lc. Trong
a. Lc cc tiu phn c kch thc ln hn l xp
nhng trng hp ny qu trn h lc
b v c. Tc dng hp ph ca l xp
khng cn l mt qu trn h c hc
n gin, c gii thch bng mt s
hin tng phc tp nh hin tng hp ph, hin tng mao dn (hnh 2.10).
Vic gi li trn m ng lc nhng tiu phn b hn kch thc l xp, cn nh cc l
xp c hnh dng khc khuu. M t khc cc tiu phn cht rn t tp trn tm vt
liu lc cng ng vai tr mt mng lc th hai.
Tc lc p h thuc vo nhiu yu t:
C th biu din tc lc ca mt cht lng qua mt m ng lc theo phng
trnh Hagen Poiseuille.

v = rcSr4( P - p )
8rjl
Trong :
r : Bn knh tru n g bnh l xp ca m ng lc
P- p : Hiu s' p lc tc dng ln hai pha ca m ng lc
s : Din tch b m t lc
r| : nht ca cht lng cn lc
1 : Chiu di l xp

67
 Phng trn h cho thy tc lc t l th u n vi din tch b m t lc, vi lu
th a bc 4 ca bn knh l xp, vi hiu s p sut tc dng ln 2 m t m ng lc,
t l nghch vi chiu di ca cc mao qun trong m ng lc v nht ca dung
dch cn lc.

3.2. C c vt li u l c, dng c l c v ph ng p h p l c
C th dng cc vt liu lc khc nhau, tu theo kch thc ca cc tiu
phn cht rn trong dung dch, tu theo tnh cht, lng dung dch cn lc v
trong mun c.
qu trn h lc c nhanh chng v th u c dch lc trong, khi la chn
vt liu lc, cn ch cc iu kin sau y :
- Vt liu lc phi c nhng l lc c kch thc n h t nh v ng nht.
- Phi bn vng v m t c hc v ha hc i vi cht em lc, (khng
tham gia phn ng ha hc vi cc cht trong dung dch, khng lm
nhim bn dch lc...)-
- Phi d ra v d phc hi kh nng lc.
- C th p dng cc phng php lc thch hp (lc nn, lc chn khng...).
C th chia vt liu lc thnh cc loi nh sau :
- Vt liu i t si cellulose (giy, bng, vi).
- Vt liu l thy tinh xp : cc m ng lc thy tin h xp.
- Vt liu lc l s xp : cc nn lc s xp.
- Vt liu lc ch to t cc cht polyme hu c tng hp (nh cc e ster ca
cellulose : cellulose acetat, cellulose nitrat...).

3.2.1. Cc vt liu v dng c lc lm t si cellulose

G iy lc: giy dng lc l loi giy khng h cu to t cellulose nguyn

cht, p th n h mng. Giy lc trong bo ch c chia lm 2 loi:
- Loi x m : cn cha nhiu tp cht nh Si20 3, Fe20 3, cc mui clorid
carbonat, trong qu trn h lc s chuyn mt phn sang dung dch, lm bn v lm
bin cht dch lc. Khi dng loi giy ny, phi ra k bng nc ct un si.
- Loi trng-, c tinh khit cao, khng cha cc tp cht nhng c nhc
im l t thm nn lc chm hn loi xm. Loi ny phn bit ra 3 loi khac
nhau:
+ Giy lc dy nhng c th th a (l lc ln) dng lc cc dung dch
snh nh siro, dung dch du,...
+ Giy lc c dy trung binh thng dng lc cc dung dch thuc.
ng knh ca cc l lc trong khong 3 - 7 miromet.

68
 + Giy lc khng tro c phm cht cao dng nh lng. C ng
knh l lc trong khong 1 - 1,5 micromet.
Giy lc cha kim loi nng c th lm bin i dung dch thuc sau khi lc.
Dung dch n a tri salicylat, cc dn ch^t phenol, adrenalin s c m u hng nu lc
qua giy lc c vt st. Giy lc cng c th hp th cc cht ta n trong dung dch
nh cc alcaloid, cc cht mu. Cc dung dch c tnh oxy ha nh iod, kali
perm anganat... c th b kh trong qu trn h lc qua giy lc.
Khi dng giy lc, bng lc phi dng cc phu thy tinh lm gi . Nu
loi cn v ly dch lc, dng giy lc c gp np v phu thy tinh c nghing
ca thnh phu l 45. Nu mun ly cn, dng giy lc khng gp np v phu
thy tinh c thnh nghing 60. Hnh 2.11 gii thiu mt s' phu lc thng gp
trong thc hnh bo ch. Loi giy lc gp np din tch b m t lc tng ln nhiu,
m t khc giy khng dnh cht vo thnh phu nn tc chy nhanh hn.

Hnh 2.11: Cc loi phu thy tinh

a. Phu lc ; b. Phu lc c rnh ; c. Phu lc nng

B n g : thng dng bng lc cc dung dch thuc dng ngoi, thuic ung...
Bng dng lc phi t cc yu cu sau: khng c m, c si di t 14 - 20
mm, khng cha acid, kim, cht kh v cc tp cht khc, c m ti a 9%;
phi thm nc sau 10 giy.
Cc v t liu loc vi, len , da: c u im l bn v m t c hc v ha hc.
Nhc im ch yu l khng cho dch lc c trong cao. Thng lc
nhng khi lng ln cc cht lng snh nh cc siro thuc.
T m loc S e z t (si cellulose kt hp am ian) t trong khung ca m ng lc c
kch thc l lc nh sau:

K hiu ng knh l lc

Ek 1,4 - 1,8 mcm

^KS 1,2 -1,4 mcm
^KSI 1,0 - 1,2 mcm
^KS2 0,3 - 1,0 mcm

69
 n g lc K N IK F I. ng lc ny do Vin nghin cu ha dc Kharcov ch to.
Nguyn tc cu to ca ng lc nh m t hnh 2 11* ong loc da tr n s
chnh lch p sut tnh, hiu su t lc c th t 30 lgi

Dch cn lc
lU t
Li hnh tr bng thp khng g
ng tr bng thp khng g c nhiu l c qun nhi lp vi
ti thnh mng lc

Dch lc

Hnh 2.1 2: S ng lc KNIKFI

3.2.2. Cc vt liu lc lm t thy tinh xp, s xp

Cc phu lc thy tinh xp c u im l tr v m t ha hc v c l lc rt
b thng dng lc dung dch thuc tim v thuc nh m t. Phu lc thy tinh
xp khng hp th cc cht trong dung dch lc, do r t thch hp i vi cc
dung dch alcaloid, enzym...
Kch thc l lc ca MT s" loi dng c lc vi cc v t liu th y tin h xp,
s xp nh sau:
- Phu lc thy tinh xp:

K hiu ng knh l lc
G - 00 500 - 200 mcm
G -0 200 - 150 mcm
G- 1 1 5 0 - 9 0 mc m
G-2 90 - 45 mcm
G -3 4 5 - 1 5 mc m
G-4 1 5 -5 mcm
G -5 1 ,5 -1 mcm

- Nn lc s xp Cham berland:

K hiu ng knh l lc
L1 8,9 - 4,7 mcm
L2 4,7 - 2,2 mcm
L3 2,2 - 2,0 mcm
L4 2 - 1 mcm

70
 3.2.3. Cc mng lc polyme tng hp
Mng lc c ch to t ester ca cellulose, nh cellulose acetat, cellulose
n itra t c kch thc l lc t 0,05 - 10 mcm, thng dng loi c l lc 0,45 mcm
lc trong dung dch thuc v m ng c l lc 0,22 mcm v khun dung dch
bng cch lc (loi b vi khun). Mt s m ng cn c ch to t nguyn liu
polyme nh teflon, polyvinylclorid, polypropylen... Cc m ng lc polyme c m t
lc cao (108 l/cm2) m bo hiu sut lc cao.
Cc phng php lc:
Theo phng trn h Hagen-Poisseuille tc cht lng i qua cc l ca vt
liu lc ph thuc vo hiu s" p sut tc dng ln hai m t ca m ng lc. Ty
theo s chnh lch p sut gia hai b m t ca m ng lc, c th chia ra ba
phng php lc:
- Lc di p su t thy tnh.
- Lc di p su t gim (lc h t chn khng).
- Lc vi p su t cao (lc nn).
Trong trng hp lc di p sut thy tnh cht lng i qua m ng lc di
p lc t l th u n vi chiu cao ct cht lng. tn g tc lc cc dung dch
snh nht c th dng bin php lc nng vi nhng phu c th n h i. gia
hai th n h phu c nc nng hoc hi nc nng lu thng, hoc t nng bng
dng in. Trong phng php lc di p su t gim ngi ta tn g hiu s p lc
gia hai b m t ca m ng lc bng cch thc hin chn khng pha di ca
m ng lc nh cc loi bm chn khng hoc sc h t ca vi nc. Khi lc cc dung
dch nng trn h lm chn khng cao v c th lm si dung dch. lc di p
su t gim, thng dng phu lc thy tin h xp, s xp, lc B uchner (Hnh 2.12,
2.13).

Hnh 2.1 3: S phu lc Buchner Hnh 2.1 4: S cc loi phu lc thy tinh xp

Khi lc di chn khng, hiu s' p su t trn v di m ng lc ch c th

t n tr s ti a 1 atm . p lc ny trong mt s' trng hp (khi l ca tm vt
liu lc ht sc nh) khng to tc lc ln. Mun c tc ln hn, phi
dng phng php lc di p sut cao ca kh nn c th n vi atm v
dung dch qua m ng lc. Thng thng ngi ta dng khng kh nn. i vi cc
cht d oxy ha nn dng kh nn tr nh nit.

71
4. Hon chnh, ng gi v kim nghim thnh phm

Dung dch thuc trc khi ng gi th n h phm, c kim tra cht lng,
phi t tiu chun cht lng ra v cc ch tiu l ha nh trong, t trng,
nh tnh, nh lng cc th n h phn dc cht, dung mi...
Dung dch thuic thng c ng l thy tin h hoc l cht do
(polyethylen, polyvinylclorid, polystyren). L thy tinh, cht do cn t yu cu
cht lng theo Dc in nh v trung tnh, khng tng k vi dc cht,
dung mi...
Cc np, n t cao su khng c hp th dc cht cng nh a tp ch t (c
trong th n h phn cao su) vo dung dch thuic.

5. Pha ch dung dch thuc theo n

Nh nu trn, cc th n h phm bo ch ni chung v dung dch thuc

ni ring theo ngun gic cng thc thuc c chia lm hai loi:
- Thuc sn xut theo l m vi s lng ln theo quy trn h sn x u t v
tiu chun cht lng c ng k vi Cc qun l Dc.
- Thuc bo ch theo n ca bc s.
Thuc sn xut theo l, c u im l cung ng c s" lng ln thuc cho
ngi bnh, cht lng ca thuc c kim sot cht ch theo l sn xut, nhng
c nhc im l khng th hon ton ph hp cho vic iu tr tng bnh nhn
do c th trn g khc nhau.
Thuc bo ch theo n ca bc s, do th n h phn v liu lng cc dc
cht c thay i ty theo th trn g tng bnh nhn, nn em li hiu qu iu
tr t't hn. Tuy nhin, vic bo ch theo n i hi ngi dc s phi c kin
thc v k th u t bo ch cng nh thc trch nhim cao m bo ch t lng
ca th n h phm.

5.1. N guyn tc cn p h i thc h in k h i pha ch 'th e o n

Kim tra n thuc m bo ng cc quy ch v khng sai st v chuyn

mn vi mt s" ni dung nh sau:
(1) Trong n thuc cn ghi r tn, tui, a ch bnh nhn, lu th n g tui
ca bnh nhn tr em.
(2) Tn dc cht, khi lng ch nh pha ch (nng , hm lng trong
n thuc).
(3) Liu lng ch nh, ng dng, cch dng m bo an ton hp l.
(4) T hnh phn v ch nh ca n thuc c vi phm cc vn tng k
tng tc thuc hay khng.
(5) Chc danh, a ch v ch k ca ngi k n.

72
 (6) Ngy k n (ngy k tn trn n thuc).
(7) Mu n thuc c m bo tnh hp php theo quy ch hin hnh hay khng.
(8) Ngi pha ch cn thc hin ng k th u t bo ch, ch m bo ng
quy ch v nhn v vt liu bao gi.
(9) Lu n thuc, vo s theo di m bo cng tc theo di qun l,
th an h tra ca c s pha ch cng nh ca cc c quan chc nng qun l
ca ngnh.

5.2. C c dung d ch m, dung d ch g c c n n g m c dng tron g p h a c h

theo n

Cc dung dch thuc thng c k n vi lng t, do trong khi pha

ch, phi m t nhiu th gi vo vic cn ong tng lng nh dc cht v ra
dng c. M t khc, cn, ong tng lng nh dc cht thng a n nhng sai
s ln.
hp l ho cc ng tc bo ch, r t ngn thi gian pha ch v nng cao
chnh xc cng nh cht lng ca ch phm , thng dng nhng dung dch
m c nng n h t nh c pha ch sn, khi iu ch mt n thuc khng
cn phi cn dc cht nguyn cht m ch dng cc dng c ong (ng ong,
buret,...) ly mt th dch dung dch m tng ng vi lng dc cht. V d
mt s" dung dch m: n a tri salycilat, n a tri sulfat 25%, kali bromid 5% hoc 10%.
Khi pha ch cc dung dch m, trn h pha cc dung dch c nng gn nng
bo ho.
Cc dung dch m ca cc ho cht bn vng c th bo qun t a trong
1 thng. N hng cht km bn vng nh cloral hydrat, urotropin ch pha dung
dch m dng trong 3 - 4 ngy, protargon, colacgon ch pha ch dng trong 1 - 2
ngy. Khng nn pha cc mui alcaloid th n h dung dch m v r t nhanh hng.
Cc dung dch m c th l mi trng r t tt cho vi khun, nm mic p h t
trin, v vy phi iu ch trong iu kin v sinh v khun. Cc chai ng v
dng c pha ch phi c tit khun trc. Dung dch m sau khi iu ch b t
buc phi lc. Sau phi nh tnh v nh lng iu chnh nng n quy
nh nu cn.
Ngi ta ci tin vic s dng cc dung dch m trong pha ch bng cch
ni lin cc bnh ng dung dch thuc vi h thng b u ret hoc ng ht. Nhng
dung dch dng vi s" lng t, c cho vo chai c cm sn ng h t c chia
hoc chai c sn ng nh git hp thc. Cc bnh ng dung dch c b u ret c
mc vo cc gi quay, cc chai nh c t trong t knh. Cc t ny c th quay
trn c th u n tin ly dung dch thuc khi pha ch. Nh p dng nhng
phng php ny hiu su t pha ch tng ln nhiu ln.

IV. MT S DUNG DCH THUC UNG V DNG NGOI

Mt s dung dch thuc ung v dng ngoi c th n h phn v k th u t bo

ch nh sau:

73
1. Dung dch thuc nc

1.1. nh ngha, phn lo i

Dung dch thuc nc (gi t t l thuc nc) l dng thuc c iu ch

bng cch ho tan mt hoc nhiu dc cht trong dung mi nc.
Thuc nc cn c mt s" tn gi ring ch cch dng thuc v mc ch
iu tr nh: thuc sc ming, thuc r ming, thuc nh tai, nh mi, thuc th t
trc trng, thuc nh mt...

1.2. K thut iu c h

1.2.1. Dng phng php ho tan thng thng

Phng php ho tan thng thng c p dng khi iu ch cc dung dch
thuc c dc cht d tan; cht t tan, c th un nng nc ho ta n nhanh.
M t s' v d:
Dung dch kim kp (dung dch Bougert) (theo DVN I):
Cng thc: N atri hydrocarbonat 0,6 g
N atri hydrophosphat 0,6 g
N atri sulfat 0,6 g
Nc ct v 200 ml
Cch iu ch: Ho tan cc dc cht trong nc ct, lc.
Dung dch acid. boric 3% (theo DVN III 2002)
Cng thc: Acid boric 3g
Nc ct v 100 ml
Cch iu ch: V acid boric t tan trong nc, ho ta n n h a n h cn ho tan
trong nc un nng. Sau ngui, thm nc va lOOml, lc.
Dung dch ng v km sulfat (dung dch Dalibour) (theo DVN I)
Cng thc: ng sulfat 1g
Km sulfat 4g
Dung dch acid picric 0,1% 10 ml
Cn long no 10% 10 ml
Nc ct v 1000 ml
Cch iu ch: Ho tan ng sulfat vo trong 900 ml nc, sau va thm
dung dch acid picric v thm dn cn long no, va thm va khuy u. Thm
nc va lOOOml. yn 24 gi, lc.

74
1.2.2. Dng phng php ho tan c bit
Cc phng php ho tan c bit c p dng nh nu trong mc k
th u t chung.
M t s v d:
D n g p h n g p h p ta o d n c h t d ta n :
Dung dch iod 1% (dung dch Lugol) (theo DVN III 2002)
Cng thc: Iod 1g
Kali iodid 2g
Nc ct v 100 ml
Cch iu ch: Ho tan kali iodid, iod trong khong 2 - 3 ml nc ct. khuy
k cho n khi tan hon ton, thm nc va 100 ml, lc nhanh qua bng.
D n g c h t d i n h o a t l m t n g ta n :
Dung dch cloroxylenol 5% (Dc in Anh 1988)
Cng thc: Cloroxylenol 50 g
Kali hydroxyd ' 13,6 g
Acid oleic 7,5 g
Du th u du \ 63 g
Terpineol 100 ml
E thanol 96% 200 ml
Nc tinh khit (va un si ngui) v 1000 ml
Cloroxylenol r t kh tan trong nc ( tan 1:3000). X phng kali ricinoleat
c to th n h t KOH v du th u du c vai tr l cht din hot lm tng
tan cho cloroxylenol. Acid oleic dng trung ho KOH cnd, m bo dung
dch tru n g tnh, khng gy kch ng n mn da. n nh dc cht. Terpineol c
vai tr trn h t a cloroxylenol khi pha thm nc do c kh nng ho tan tt
eloroxylenol, m t khc to mi c tr ng cho dung dch thuc, ethanol l dung
mi m bo cho phn ng to x phng xy ra nhanh.
Cch iu ch: Ho tan KOH trong mt ng nc ti thiu, thm dung
dch du thu du trong ethanol. khuy k (khong 1 gi) cho n khi th 1 phn
nh hn hp vi 19 phn th tch nc to c dung dch trong. Thm acid oleic
trung tnh dung dch x phng.
Ho tan cloroxylenol trong phn ethanol cn li. Dung dch ny c khuy
trn vi tex-pineol v dung dch x phng. Va khuy lin tc va thm dn lng
nc cn li cho th tch lOOOml.
Dung dch cloroxylenol 5% trong sut nhng s to nh dch c trn g khi
pha long (20 ln), dng st khun da.

75
1.2.3. Trng hp dung dch thuc c cc cht phn ng vi nhau to ra cht c tc
dng dc ly

C mt s' dung dch thuc khng i t dc cht c sn pha ch m dc

cht c to ra trong qu trnh pha ch.
M t s' v d:
Dung dch ch acetat base :
Ch acetat 30 g
Ch oxyd 10 g
Nc 7g
Ch acetat base c to th n h theo phn ng sau y:
Pb(CH3C 0 0 )2.3H20 + PbO -> Pb(CH3COO)2.Pb(OH)2+ 2H20
Phn ng ny xy ra r t chm nhit thng, v vy phi iu ch dung
dch nhit cao theo phng php sau y:
Ho tan ch acetat vi 80ml nc ct trong mt bt s. Thm ch oxyd tn
mn v un, ng thi khuy lin tc cho n khi hn hp m t m u. y bt,
lng mt lt, sau lc vo chai. Trong khi lc ch y phu.
Khi dch lc ngui, thm nc ct cho 100 g hoc cho n khi t t
trng 1,30 - 1,32.
Khi iu ch dung dch ch acetat base cn dng nc khng c C 0 2 v ch
acetat base phn ng vi C 0 2 to ch carbonat khng tan.

2 [Pb (CH3COO)2 .Pb (OH)J + C 0 2 - P bC 03. Pb (OH)2 + 2Pb (CH3COO)2 + H20

tr n h nc hp th mt lng ln C 0 2 t khng kh, lc b t u un
ngi ta ch ha tan ch acetat trong mt lng nc n h t nh cn th i t thu
c ch acetat base. Phn nc cn li s cho vo sau khi phn ng k t thc.
Cn ch khng nn un lu qu lm ch acetat s b phn hy cho acid acetic v
d b carbonat ha.
Dung dch ch acetat base l mt dung dch trong sut, khng m u, v hi
ngt se, c phn ng kim nh. D b carbonat ha trong khng kh. Bo qun
dung dch trong l kn.
Dung dch ch acetat base phi cha 13,5 - 14,8% ch.
T dung dch ny, ngi ta pha nc ch acetat base:
Dung dch ch acetat base 2g
Nc thng v 100 ml
Trn u, th u c mt cht lng trn g nh sa do ch carbonat, sulfat,
clorid khng tan mi c to th n h . Nc ch acetat base cha 0,28% ch, dng
p cc vt thm tm.

76
 D ung dch kali asenit 1% (dung dch Fowler) (theo DVN I):
Thnh phn c As20 3 (lg), K2C 0 3 (lg). Tinh du qu (1 git) lm thm,
ethanol 10ml, HC1 10% va trung tnh, nc va 100 ml. As20 :i phn
ng vi K2C 0 3 khi un nng to ra K A s02.

1.2.4. Trng hp trong dung dch thuc c cht lm gim tan ca dc cht
Nh nu trong mc k th u t chung, cc cht to mui km tan vi dc
cht, cc cht in gii, c ion cng tn lm gim tan ca dc cht trong dung
dch. Cn pha long nng cc cht ny khng gy kt t a dc cht khi ha

V d :
Rp. Codein phosphat 0,5 g
N atri bromid 10 g
Nc v. 200ml
M.f. Sol
Trong dung dch c m t ion bromid, codein phosphat d tan ( tan 1 : 3,5)
chuyn th nh codein hydrobromid t tan ( tan 1 : 100) cn ha tan ring, pha
long ri phi hp hai dung dch dc cht.

1.3. ng g i v kim nghim thnh phm

Quy nh c th ring cho tng ch phm thuc nc.

2. Siro thuc

2.1. nh ngha, p hn lo i

Siro thuc l nhng ch phm lng snh, trong ng chim t l cao

(khong 56 - 64%), c iu ch bng cch ha tan dc cht, dung dch dc
cht trong siro n hoc ha tan ng trong dung dch dc cht, dng ung.
Siro thuc c mt s' u im nh: C th che du c v kh chu ca
mt s dc cht, thch hp dng cho tr em, vi hm lng ng cao c th hn
ch s pht trin ca vi khun nm mc.
Theo cch ha tan ng, siro c chia lm 2 loi: Siro iu ch nng v siro
iu ch ngui.
Theo mc ch s dng, phn ra loi siro dng lm cht dn v siro thuc.
Siro thuc c cha dc cht c tc dng iu tr bnh. Siro dng lm cht dn
khng c cha dc cht, ch c cc cht lm thm, iu v (nh siro n, siro v
cam, siro cnh kin trng) dng phi vi cc dc cht khi pha ch thuc.

77
 2.2. Thnh phn

Thnh phn chnh ca siro thuc bao gm cc dc cht, dung mi nc v

ng. Siro thuc c th cha mt hoc nhiu loi ng nh sacharose, glucose,
ructose, sorbitol, manitol, saccharin.
- Cc cht lm tng tan, tng sinh kh dng v n nh cua siro
thuc nh: glycerin, propylen glycol. ethanol.
- Cc cht lm tng nht nh Na CMC, PEG 1500...
- Cc cht to h m pH, iu chnh pH, nhm m bo n inh cho
dc cht nh acid citric, acid tartric, HC1. NaOH...
- Cc cht chng oxy ha nh Na.,EDTA, n atri m etabisulfit...
- Cc cht bo qun chng nm mc: Nipagin, nipasol.
- Cc cht mu, cht lm thm...

2.3. K thut iu ch
2.3.1. iu ch siro thuc bng cch ha tan dc cht, phi hp dung dch dc cht vo
siro n
Cch iu ch ny thng p dng cho trng hp cc siro thuc c dc
cht d tan trong siro n, cc dc cht c cn phi ha tan trong mt dung mi
thch hp sau phi hp vi siro n, m bo ng hm lng cc dc cht.
Cc giai on tin hnh nh sau:
iu chsiro n:
Siro n c th c iu ch bng cch ha tan sacharose trong nc nng
hay ha tan nhit thng.
- Cng thc siro n khi iu ch bng cch ha ta n nng: 16 g ng,
lOOg nc. Saccharose c ha tan trong nc t trn ni cch thy, n h it
khng nn qu 60c. Lc nng siro n qua nhiu lp vi gc. Kim tra t trng
ca siro n 105c l 1,26 (hoc 20c l 1,314) tng ng vi nng 64%
ng c trong siro n.
- Cng thc siro n iu ch nhit thng: 180g ng. lOOg nc.
Saccharose c t trong ti vi nhng ngp b m t nc, yn, qu trnh
ha tan t xy ra theo cch i lu t trn xung. Khi ng ha tan ht mi
khuy u, th u c siro n c nng ng cho theo cng thc (do khng c
s bay hi dung mi nh khi ha tan nng). C th dng dng c kiu bnh ngm
kit iu ch siro n nhit thng.
Cc siro n ca cc loi ng c iu ch tng t nh tr n vi hm
lng ng ty theo cng thc (nh siro ng sorbitol 70%, glucose 60%...).
Chun bi dung dch dc cht (nu c):
Trong th n h phn siro thuc nu c cc dc cht c bng A hoc bng B
cn phi dng mt lng dung mi thch hp ti thiu ha tan. to th n h dung

78
dch dc cht. Cc dc cht c thng c hm lng nh, mt lng nh dung
dch cc dc cht c nh hng khng ng k n nng ng trong siro,
nhng m bo cc dc cht c ha tan hon ton, trn u ng n h t
trong siro thuc.
Mt s' dch chit dc liu c c c th u n tin khi pha siro thuc theo
cch phi hp vi siro n. Thng t l phi hp dch chit m c v siro n l
1 : 10 .
Ha tan dc cht, phi hp dung dch dc cht v siro n:
Siro n c nht cao, cn un nng d dng ha tan cc dc cht. Vic
ha tan cc dc cht vo siro n c u im khng lm gim t l ng v nc
c trong siro thuic.
Cc dung dch thuc c iu ch vi dung mi nc hoc th n nc (nh
ethanol, glycerin, propylen glycol...) d dng phi hp trn u ng n h t vi siro
n.
Cc cht ph khc c trong thnh phn c ha tan vo dung dch thuc
hoc siro n mt cch hp l ty theo vai tr ca cht ph v tnh cht ca dc
cht.
Hon chnh thnh phm :
Siro thuc c lc trong (lc nng), kim nghim phi t cc ch tiu ra
trc khi ng gi th n h phm.

2.3.2. iu ch siro thuc bng cch ha tan ng vo dung dch dc cht

Cch iu ch nv thng c p dng iu ch phn ln cc siro thuc
do th u n li cho vic pha ch cc dung dch dc cht, cng nh ha tan cc cht
ph, cc loi ng khc nhau c trong cng thc.
Cc giai on tin hnh nh sau:
Chun b dung dch dc cht:
Dung dch cc dc cht c th c pha ch bng phng php ha tan
thng thng hay ha tan c bit. Cc dch chit iu ch bng cch chit xut
dc liu, hoc ha tan t cao thuc. Dung mi cht dn l nc thm c iu
ch bng cch chng ct, mt s* cht ph khc c ha ta n giai on ny
nhm n nh dung dch thuc hoc tng tan ca dc cht.
Ha tan ng vo dung dch dc cht:
ng c th c ha tan nng hoc nhit thng vo dung dch dc
cht, nh nu khi iu ch siro n.
Cch ha tan nng c u im l nhanh v d lc siro thuc, nhng khng
p dng c khi dc cht d phn hy bi nhit. Siro thuc iu ch nng
thng m m u hn do hin tng caram en ha. c ng kh do thy phn
saccharose.

79
 a nng ng n gii hn quy nh:
Nng ng trong siro c th c xc nh bng cch o t trng hoc o
nhit si, do c tng quan gia nng - t trng, nng - n hit SI (bang
2.4 & bng 2.5).

Bng 2.4. T trng ca siro n v nng ng 15c

Nng ng (%) T trng Siro

65 1,3207

64 1,3146

60 1,2906

55 1,2614

Bng 2.5. Mi quan h gia nng ng v nhit si ca dung dch ng

saccharose trong nc

Nng ng (%) Nhit si (C)

10 100
20 100,6
30 103,6
6 4 -6 5 105
80 112

Cch o nhit si xc nh nng ng mc sai s ln do n h it

si thay i khng nhiu khi thay i nng . Dng t trng k hoc dng cch
cn mt th tch xc nh siro c th o c t trng ca siro. V d: 1 lt siro n
saccharose c nng 64% 20c phi c khi lng 1,314 kg.
Loi ph k chia theo Baume, c tng quan vi t trng nh trong bng 2.6:

Bng 2.6. Tng quan gia Baume v t trng

Baume T trng Baume T trng

28 1,2407 34,5 1.3100
29 1,2515 35 1,3202
30 1,2624 36 1,3324
31 1,2736 37 1,3448
32 1,2849 38 1,3574
33 1,2964 39 1.3703
34 1,3020 40 1,3834

80
 Cch tnh lng nc cn thm vo siro c nng cao qu quy nh nh
sau (tnh ra gam):
ad2( d ,- d )
d ,( d - d 2)
Trong :
X: Lng nc cn thm (g)
a : Lng siro cn pha long (g)
d2 : T trng nc = 1; (nu dng siro c nng thp c t trng d2 thay
cho nc, khi X l lng siro nng thp cn ly thm vo
siro nng cao).
dj : T trng ca siro cn pha long.
d : T trng quy nh ca siro cn t c.
Khi dng ph k Baume, lng nc cn dng pha long siro n nng
quy nh c tn h theo cng thc :
x = 0,033 a.D
Trong : X : lng nc cn dng pha long
a : Lng siro (g)
b : S' Baume o c ca siro cn pha long vt qu 35 Baume
Lm trong siro:
Siro thuc cn c lc nng qua nhiu lp vi gc, vi d, loi giy lc c
bit dy v xp, c l lc ln c th c dng lc siro thuc.
Nu i t dch qu, dch chit dc liu, vic lm trong c th phc tp hn
do cc cht kt t a dng cc h t keo. v nguyn tc cc dung dch dc cht cn
c lc trong trc khi ho tan ng. Nu dng cch un nng khng lm ng
vn cc t a keo c th p dng cc bin php lm trong nh sau:
- Dng bt giy lc: lg bt giy nghin th n h bt nho trong ci s vi mt
t nc nng, vo 1000 g siro ang nng, un si vi pht. Sau lc qua vi.
Cch ny c u im khng a tp cht l vo siro thuc.
- Dng lng trn g trng: mt lng trn g tr ng dng cho 10 lt siro. Ho
tan lng trn g tr ng trong siro, khy trn, album in lng trn g tr ng s k t t a li
cun cc tiu phn nh l lng kh lc trong siro. Ht b k t ta, lc siro qua vi.
Cch ny c nhc im a mt s' protein phn t nh ta n c vo trong siro,
c th gy tng k vi dc cht.

2.4. K im s o t ch t tng - bo qun

Siro thuc c quy nh cc ch tiu cht lng v tn h cht l ho theo

Dc in nh trong, t trng, nh tnh, nh lng cc th n h phn dc
cht...

81
 bo qun, trong thnh phn so thuc thng c cc ch t chng n a m
mc nh nipagin, nipasol (t l 0,03 - 0,05%). Siro thuc c ng chai l kin.
khng nn ni lnh v c th kt tinh ng trong siro.

2.5. M t s v d s iro thuc

2.5.1.iu ch siro thuc bng cch ho tan ng vo dung dch dc cht

a. Siro iodotanic (theo DVN I, tp I)

Iod 2g
Tanin 4g
Nc ct 400 g
ng trn g 600 g
Tn nh iod cho vo bnh thu tinh. Thm tam in, nc theo s lng ghi
trn v 100 g ng. un cch thu gn 60c, th n h thong khuy. Khi od a
tan ht v dung dch khng cn phn ng vi giy h tin h bt, cho lng ng
cn li vo bnh v tip tc un cch thu cho tan ht ng.
Ch phm m u nu , v ngt, sn.
Siro ny c t trng 1,30 20c.
C th iu ch siro iodotanic theo cng thc sau:
Iod 0,1 g
Kali iodid 0,1 g
Nc 1g
Acid tanic 0,25 g
Glycerin 5g
Siro gm 25 g
Siro n v. 100 g
Ho tan iod v kali iodid trong nc v trn vi dung dch ta n in trong
glycerin. Sau thm siro gm v 5 g siro n. un cch thu hn hp 60c.
Thnh thong khy cho n khi lm l hn hp pha long vi lOml nc ct khng
cn cho phn ng vi h tinh bt. Thm lng siro n cn li v trn u.
b. Siro cnh kin trng (theo DVN I, tp I).
Cnh kin trn g 30 g
Nc ct 500 ml
Dung dch amoniac 1% 700 ml
ng trn g 1800 g

82
 Tn nh cnh kin trng trong c s, cho vo b t s c np, thm 500 ml
nc, un cch thu si trong 2 gi lin, thnh thong khuy bng a thu tinh.
ngui gn ly nc v lc qua vi tha.
Thm 500 ml dung dch amoniac 1% vo b, un cch thu si trong 1 gi
thnh thong khuy. ngui, gn nc, lc qua vi th a ri tp tru n g vo dch
sc u.
Chit mt ln na bng 200 ml dung dch amoniac 1% theo cch trn, cui
cng vo dch sc tp trung trn cho va 1000 ml.
Thm 1,8 kg ng vo 1000 ml dch sc, y kn, un cch thu, thn h
thong khuy cho ta n ht ri lc qua vi. Siro th u c lng snh, m u vng hi
nu, c th hi c l, mi thm cnh kin trng, thong m i vani, v ngt.
T trng 25C: 1,298 - 1,32
c. Siro st I I sulfat (theo USP 23)
S t II sulfat 40 g
Acid citric 2,1 g
Cn bc h 2 ml
Saccharose 825 g
Nc ct v. 1000 ml
Ho tan s t II sulat, acid citric, cn bc h v 200 g saccharose trong 450ml
nc, lc dung dch th u c. Ho tan phn ng cn li trong dch lc, thm
nc 1000 ml (lc li siro nu thy cn thit). Bo qun trong l kn, tr n h nh
sng.
d. Siro loratadin 0,5%
L oratadin 0,1 g
Propylen glycol 7,2 g
Glycerin 18,0 g
Acid citric khan 0,7 g
N atri benzoat 0,1 g
Saccharose 54 g
C ht m u v
C ht lm thm v
Nc tin h k hit v. 100 ml
L siro thuc c tc dng khng histam in m nh, tc dng ko di, iu tr
vim mi d ng, s mi thi tit, vim da d ng, m y ay.

83
 e. S iro terbulatin 0,3%
Cng thc: Terbutalin sulfat 0,3 g
Glyceryl gaiacolat 13,3 g
Nipagin 0,9 g
Nipasol 0,2 g
Saccharose 600 g
Glycerin 125 g
N atri dihydro phosphat 1,2 g
Acid citric khan 1,2 g
C ht thm v
Nc tinh khit v. 1000 ml
L siro thuc c ch nh iu tr hen ph qun, vim ph qun, kh ph
thng v cc bnh phi khc c km co tht.

2.5.2. iu ch siro thuc bng cch ho tan dc cht, dung dch dc cht vo siro n

a. Siro cloral (theo DVN I, tp I)

Cng thc: Cloral hydrat kt tinh 5,0 g
Nc 4,5 g
Cn bc h 0,5 g
Siro n 90,0 g
Ho tan cloral hydrat trong nc, thm cn bc h, siro n, k h u y u.
C ht lng snh, khng mu, mi bc h, v ngt, hi ng. T trng khong
1,306 1,314.
6. Siro Brocan (52 TCN - 217 - 87)
Cng thc: Calci bromid 2,25 g
Cloral hydrat 0,39 g
Siro n v. 100,0 g
C tc dng an thn, gy ng
c. Siro dextromethophan 0,3%
Cng thc : D extrom ethophan hydrobrom id 0,30 g
Nipagin 0,045 g
Nipasol 0,029 g
Ethanol 0,250 g

84
 Dung dch glucose 60% 100,00 g
NaOH v. pH 4,75
C ht thm v
Nc tinh khit v. 100 ml
Thuc c tc dng du ho khng gy nghin thay cho codein v cc ch phm
cha morphin gy nghin.
d. Siro bromhexidin
Bromhexidin hydroclorid 0,08 g
Carboxymethyl cellulose 0,35 g
Glycerin 2g
Acid benzoic 0,1 g
Propylen glycol 5g
N atri saccharin 0,03 g
N atri cyclamat 0,3 g
Acid tartric 0,16 g
Dung dch sorbitol 70% 25,8 g
Ethanol 2,7 ml
C ht mu, cht thm v.
Nc tin h khit v. 100 ml
L siro thuc c tc dng tiu cht nhy, ch nh iu tr vim th an h qun
km hen,...

2.5.3. Siro dng cho ngi bnh tiu ng

Nhng ngi b bnh tiu ng khng c php dng ng. vn c
th cho ngi bnh s dng mt s thuc di dng siro, ngi ta thay siro n
iu ch t ng saccharose bng siro c cng thc nh sau:
N atri carboxym ethyl cellulose 1g
Nipagin 0,2 g
Saccharin 0,2 g
Ethanol 2 ml
Nc v. 100 g
Ho tan nipagin v saccharin trong ethanol. Rc n a tri carboxym ethyl
cellulose ln m t nc, thnh thong khuy cho n khi ho ta n hon ton. Thm
dung dch nipagin v saccharin trong ethanol. Trn u.
C ht lng snh, khng mu, v ging siro n.

85
3. Thuc nuc chanh

3.1. nh ngha

Thuc nc chanh l nhng dung dch acid, mui hu c, v c, c lm

ngt, lm thm v i khi c hi C 0 2 dng ung gii kht, trong th n h phn c
mt s' dc cht.
Thuc nc chanh c tc dng iu tr thng l thuc nc chanh ty, nc
chanh acid gii c kim, thuic nc chanh chng nn.

3.2. K thut iu c h

Dung mi pha thuc nc chanh l nc ct.

Cc acid tham gia vo thnh phn thuc nc chanh c th l acid hu c hoc
v c (acid sulfuric, acid tartric, acid citric,...)- Cc mui thng dng magnesi
citrat, n a tri ta rtra t, kali b ita rtra t. Mun nc chanh c hi C 0 2 (gas) c th sc
C 0 2 vo thuc nc chanh iu ch hoc c th to C 0 2 ngay trong dung dch
bng cch cho n a tri hydrocarbonat phn ng vi acid c trong dung dch.
Thuc nc chanh thng c iu ch bng cch ho ta n v trn ln cc
cht c trong cng thc. i vi thuc nc chanh c hi, lng C 0 2 trong dung
dch ph thuc vo th n h phn v cch iu ch. Nu ho ta n natri
hydrocarbonat, sau ho tan acid, C 0 2 to th n h s m t i m t p h n ln.
Nu pha ring cc dung dch n a tri hydrocarbonat v acid, v ch trn ln
trc khi dng, c th gi c lng C 0 2 nhiu hn. Tuy nhin cng c th trn
chung acid v n a tri hydrocarbonat kh vo mt chai c th n h dy, c sy
kh, c dung tch gp 2 ln th tch dung dch thuc nc chanh cn pha ch. Sau
thm siro. Cho nc hoc dung dch dc cht vo chai sau cng. y n t m
bo kn.
C th lc cc thuc nc chanh khng c hi. Thuc nc chanh c hi
thng khng lc. Khi cn c th lc ring cc dung dch acid v natri
hydrocarbonat trc khi trn ln vi nhau.
Dung dch thuc nc chanh do cha mt lng ng n h t nh, l mi
trng th u n li cho vi khun, nm mc p h t trin. V vy, ch pha ch khi dng.
C th bo qun mt hai ngy ch mt.
khc phc nhc im chng hng v d m t C 0 2 ca thuc nc chanh,
hin nay sn xut cm hoc vin si bt c th n h phn tng t (acid, cc
mui, n a tri hydrocarbonat, ng, cht lm thm,...). Khi dng ho ta n cm hay
vin vo nc ct hoc nc un si ngui.

3.3. M t s v d

3.3.1. Pha ch thuc nc chanh acid citric c hi

Cng thc:
- Dung dch 1:

86
 N atri hydrocarbonat 4,0 g
Siro n 15,0 g
Nc v 100 ml
- Dung dch 2 :
Acid citric 3,5 g
Siro acid citric 15,0 g
Nc v. 100 ml
Trong mt chai ho tan n a tri hydrocarbonat trong nc sau thm siro
n. Trong mt chai khc, ho ta n acid citric ri thm siro n.
Khi dng, ung mt tha dung dch 1, sau ung mt tha con dung dch 2.
Kh carbonic to th n h ngay trong d dy, c tc dng chng nn.
Nu mun pha ch (ch ng vo mt chai), dng cng thc sau:
Acid citric 15,0 g
N atri hydrocarbonat 2,0 g
Siro n 15,0 g
Nc v. 100 ml
Cho acid citric v n a tri hydrocarbonat vo y chai. Thm siro. Sau cho
nc t t v cn th n vo chai tr n h xo trn lp nc siro. y n t kn, lc
trc khi dng.

3.3.2. Thuc nc chanh ty magnesi citrat

Cng thc: Acid citric 32 g
M agnesi hydrocarbonat 20 g
Nc ct 300 ml
Siro n 75 g
Cn v chanh ti 1g
Ho tan acid citric trong mt b t s. C th un nng acid citric chng
tan. Thm t t m agnesi hydrocarbonat, va thm va khuy. Khi phn ng
kt thc (ht si bt), lc dung dch ny vo chai c sn siro n v cn chanh
ti. y nt.
Mui ty magnesi citrat c to thnh do phn ng ca magnesi hydrocarbonat
vi acid citric.
Nu khng c m agnesi hydrocarbonat c th th ay bng m agnesi oxyd 8,80 g.
Ch phi ghi lng m agnesi c itrat c trong cng thc trn nhn. D n n h n
ph "lc trc khi dng".

87
3.3.3. Thuc nc chanh ty natri tartrat

Cng thc: Acid tartric 20 g

N atri hydrocarbonat 22 g
Siro acid tartric 60 g
Nc ct 400 ml
Cho 5 g acid tartric vo chai. Sau cho ton lng siro acid ta rtric vo
chai. Ho tan ring n atri hydrocarbonat vo mt t nc, ri thm lng acid
tartric cn li. Khuy k. Lc dung dch vo chai. y np kn.
Dung dch trong sut, khng mu, v ngt hi chua.
Cng thc trn cho mt thuc nc chanh c 30 g n a tri ta rtra t. M un c
nhng lng n a tri ta rtra t khc nhau, phi tnh lng acid ta rtric v n a tri
hydrocarbonat cn dng.
Ch iu ch dung dch khi cn. Trn nhn ghi lng n a tri ta r tr a t c trong
cng thc v dn nhn ph "lc trc khi dng".

4. Nc thm

4.1. nh ngha

Nc thm l nhng ch phm th u c bng cch ct dc liu hoc bng

cch ho tan tinh du trong nc. Nc thm cha nhng hot cht d bay hi
ca dc liu thc vt nh tinh du, cc acid bay hi (izovalerianic, cyanhydric,...)-
Trong bo ch, nc thm thng c dng lm cht dn hoc dung mi
cho mt s dc cht c mi kh chu. Ch mt s nc thm c tc dng dc l
nh nc thm l o, nc thm bc h, h nh nhn ng.

4.2. K thut iu c h

iu ch nc thm thng dng dc liu ti hoc kh c cha cc hp

cht d bay hi hoc cc tinh du.
Khi ct dc liu ti s th u c th n h phm trong v thm. N hng i vi
mt s' nc thm (qu, inh hng...) ch c th th u c th n h phm t t khi s
dng dc liu kh.
Cc cht bay hi v tin h du thng c trong nhiu b p h n khc n h a u ca
thc vt nhng hay gp n h t l hoa, l v v. c n phi th u hi dc liu ng
lc: Hoa nn thu hi lc sp n, l th u hi lc cy sp ra hoa hoc chm ra hoa,
qu th u hi lc bt u chn, r cn h n h thng c th u hi khi cy p h t
trin hon ton.
Nu iu ch nc thm bng cch ho ta n tin h du trong nc, phi dng
loi tin h du tt, khng dng nhng loi tin h du qu lu, b oxy ho do
nh hng ca khng kh v nh sng, b bin m u v thay i m i v.

88
4.2.1. Phng php ct ko bng hi nc

iu ch nc thm t cc dc liu mng m anh (hoa, l...) thng dng

phng php ct ko bng hi nc. Dng c ct ko bng hi nc bao gm b
phn to hi nc, b phn cha dc liu v b phn ngng t ni lin vi bnh
hng. Hi nc c dn t b phn un si, sc vo nc ngm dc liu, li
cun cc tinh du v cht thm bay hi sang b phn ngng t to th n h nc
thm.
Phng php ct ko bng hi nc c u im l dc liu ch tip xc vi
hi nc, khng tip xc vi y ni un, trn h c hin tng qu nng lm hng
dc liu v lm nc thm c mi kht, c n ch l trc khi ct, dc liu phi
c chia nh thch hp (hoa, l c bt th; r, ht, qu nghin mn va).
quy m ln, n h t l vi dc liu rn chc, ngi ta dng phng php
ct trc tip. Dc liu v nc c cho thng vo ni un. dc liu khi tip
xc vi y ni, thng t v hoc sng cch xa y ni. Cng c th cho dc
liu vo gi ngp trong nc. i vi dc liu r n chc, tin hnh ngm dc
liu trong 24 gi vi nc ri mi tin hnh ct.
Khi ch nc thm bng phng php ct, cn ch trong giai on u,
dc liu cn cha nhiu tin h du, nn ch un nng va phi, m t khc b phn
ngng t phi lnh tr n h hao h t tinh du. Nu tin hnh ct qu nhanh,
t l tinh du trong th n h phm s thp. Thng thng nhng phn nc thm
hng c u tin cha nhiu hp cht th n nc (aldehyd, alcol, cc acid...) v
c mi thm d chu.
Nc thm hng c cn lc k, sau yn v gn tinh du khng tan
(nu c) bng bnh gn. Lc nc thm qua giy lc hoc bng thm t vi nc.

4.2.2. Phng php ho tan tinh du trong nc

V nc thm th u c bng phng php ct thng kh bo qun v cng
vic iu ch i hi nhiu thi gian nn ngi ta dng cc phng php ha
tan iu ch nhanh chng nc thm.
C th iu ch nc thm bng cch pha long mt dung dch tinh du
cn vi nc. Dung dch tinh du cn c pha ch theo cng thc sau:
Tinh du 1g
Ethanol 90 v. 100 ml
Mun iu ch nc thm, trn 3 ml dung dch trn vi 97 ml nc ct,
khuy k v lc.
Mt phng php iu ch khc l dng cht trung gian phn tn tinh du
trong nc. Cc cht trung gian thng dng l: bt talc, kaolin, bt giy lc...
Tinh du 1g
Nc ct v. 1000 ml
Bt talc 10 g

89
 Nghin trn bt talc vi tinh du. Sau thm nc v k huy lc k. yn
24 gi, thn h thong khuy. Sau lc dung dch qua giy lc th m nc.
H s tan ca cc tinh du trong nc l 0,05 tng ng vi nng 0,5 g/1.
Trong cng thc trn phi dng tha tinh du v nc ch ho ta n cc phn thn
nc m r t t ho tan cc phn s nc v cc hydrocarbon kiu terp en c mt
trong tinh du. y, bt talc ng vai tr cht gy phn tn. Nc thm iu
ch bng phng php ny thng khng c trong do cc tiu p h n tin h du
hoc bt talc lt qua giy lc. Gp trng hp ny cn phi lc li ch phm.
Nhc im ca phng php l bt talc hp ph mt lng ln tin h du.
Mc d nc thm iu ch bng phng php ny khng c m i thm d
chu nh nhng ch phm thu c bng phng php ct, nhiu Dc in vn
quy nh dng phng php ny v bo m c nng tin h du xc nh v
cho php iu ch c tng lng nh nc thm.
Trong nhng nm gn y, nhng cht din hot kiu Tween c dng
ngy cng nhiu ho tan tin h du trong nc khi iu ch nc thm . Cng
thc nc thm i t tinh du nh sau:
Tinh du 2,0 g
Tween 20 20,0 g
Ethanol 200,0 ml
Nc ct v. 1000,0 ml
Cc th n h phm iu ch vi Tween lm cht tru n g gian ho ta n c mi
thm m nh hn, nng tin h du xc nh v c th bo qun c lu hn.

4.3. K im so t ch t lng, b o qun n c thom

Nc thm thng trong, khng m u, c mi c bit ca dc liu hoc

tinh du dng iu ch. T trng ca nc thm xp x t trng ca nc ct,
pH tru n g tnh hoc hi acid.
Tr nc l o v nc ct qu c hot cht xc nh, a s cc nc thm
khc cha khong 0,03% tin h du. nh lng tin h du bng phng php chit
hoc ct.
Nhng yu t phn hu nc thm l n hit , n h sng, khng k h v vi
khun, nm mc. Di tc dng ca n hit cao, mt p hn tin h du c th bay
hi, nh sng v khng kh oxy ho tin h du lm nc thm c m i k h t v tr
nn acid hn. Vi khun, nm mc p h t tri n trong nc thm lm ch phm thay
i mi, v, m u sc.
Cn ng nc thm trong l thu tin h m u, n t kn, ch m t. C th
thm nipagin, t l 0,05% bo qun.

90
4.4. M t s v d n u c tham

4.4.1. Nc thm l o
Cng thc: L o ti 100 g
Nc ct 400 ml
Ct nh, gi dp l o cho vo dng c ct ko bng hi nc. Tin hnh
ct v hng 100 ml nc thm. Lc nc thm qua giy lc thm nc.
Sau khi ct xong phi nh lng acid cyanhydric ton phn (kt hp v t
do). Nc thm l o phi trong, mi d chu, cha 0,1% acid cyanhydric. ng
l y, n t kn, ch ti.

4.4.2. Nc thm bc h
Cng thc: Ngn bc h ti 100 g
Nc ct v.
Ct nh ngn bc h. Ct ko vi hi nc. Hng ly 100 g th n h phm . Nu
khng c bc h ti, dng bc h kh, 20 g bc h kh ng vi 100 g bc h ti.
Thnh phm l cht lng hi c, m i bc h, v m t d chu. 100 ml nc
thm bc h cha 0,03 - 0,04% tinh du.
C th iu ch nc thm bc h bng phng php ho tan tinh du nh sau:
Tinh du bc h 1,5 g
Nc ct v. lOOml
Bt talc 15 g
Nghin tinh du bc h vi bt talc, sau lc m nh vi nc ct un si
ngui n 40 - 50c. yn 24 gi. Thnh thong khuy. Sau lc qua giy lc
thm nc. Dung dch trong hoc hi c, khng m u, c m i v bc h.

4.4.3.Nc thm tiu hi

Cng thc: Tinh du tiu hi 2g
Tween 20 20 g
E thanol 90 300g
Nc ct 678 ml
Trn tin h du tiu hi vi Tween 20. Thm ethanol. Thm dn nc ct
un si ngui n 40 - 50 c, va thm va khuy cho n khi dung dch trong
hon ton.

5. Potio
5.1. nh ngha, phn lo i

Potio l dng thuc nc ngt, cha mt hay nhiu dc cht, thng pha
theo n v cho ung tng tha (10 - 15ml).

91
 Cc potio thng hay gp trong pha ch theo n, tuy vy cc Dc in
cng c quy nh mt s cng thc potio nh: potio cn qu, potio chng nn...
C th phn potio thnh 3 loi:
- Potio chnh tn (potio dung dch)
- Potio hn dch
- Potio nh dch
Dung mi v cht dn ca potio l nc, nc ct thm, nc hm hoc nc
sc dc liu. Cng c trng hp dng cn thp (potio cn qu).
Dc cht tham gia vo th n h phn ca cc potio r t a dng. C th l cc
cn thuc, cao thuc, cc ho cht d tan trong nc hoc t tan trong nc, cc
ho cht d bay hi (ether, ethanol, tinh du...).
Ngoi ra trong th n h phn cc potio cn c cc cht lm ngt (siro n, siro
thuc hoc hn hp cc siro).
Nh nu, trong cng thc ca potio c th c cc cht khng ta n trong
nc phi phn tn di dng hn dch mn hoc nh tng (potio n h dch).
Potio hn dch, potio nh dch p dng cc phng php iu ch hn dch,
nh tng s c nu trong chng hn dch, nh tng.

5.2. K thut iu c h

V th n h phn ca cc cht phc tp nn kh c th ra mt phng php

iu ch chung. Sau y ch nu ln mt s' im cn ch trong khi iu ch
dng thuc potio ny.
- Nu trong potio c cn thuc, cao lng, phi trn k cn thuc, cao lng
vi lng siro c trong n trc khi thm cc dc cht khc v ch t dn. Nu
lng cn thuc di 2 g, c th ly theo git, bng ng m git hp thc. Nu
lng cn thuc qu 2 g, phi dng cn.
- Cc cao mm v cao c thng c ho ta n trong siro nng hoc
glycerin.
- Nhng dc cht tan c trong trong dung mi v cht dn thng c
ho tan trc ri lc vo chai.
- i vi cc potio c dc liu, phi un si nc sc hoc hm dc
liu. Nu khng c ch dn c bit, t l dc liu, thng dng ch nc sc
hay nc hm l 2% (dc liu l l hoa) v 4% (dc liu l g, thn, r).
- Nu trong potio c tinh du, phi nghin tinh du vi ng p hn tn
u tinh du, ri trn vi lng siro c trong cng thc.
Khi iu ch potio cn ch tr n h cc tng k c th xy ra, n h t l cc
tng k ho hc.

92
 Do cha mt lng nh ng, cc potio l mi trng th u n li cho s pht
trin ca vi khun, nm mc. Ch nn iu ch khi dng hoc dng trong 1 - 2
ngy, ng vo chai 60 - 125 ml. Nn bo qun cc potio trong chai n t kn,
ch mt.

5.3. M t s v d

5.3.1. Potio cn qu (theo DVN, tp I)

Cng thc: c n qu 4 ml
Ethanol 20 ml
Siro n 20 ml
Nc ct v. lOOml
Ho cn qu vi ethanol. Thm siro, khuy u. Thm nc va lOOml.
Trn u.
Dung dch m u da cam, mi qu, v ngt v cay.
Bo qun trong chai kn.

5.3.2. Potio gm
Cng thc: Bt gm arabic 10 g
Siro n 10 ml
Nc ct v. 150ml
Nghin gm vi siro. thm nc hoa cam, ri thm nc ct v 150 ml.
Cht lng trong hoc hi c, m u vng nht, v ngt mi hoa cam.
C th iu ch potio gm theo cng thc sau:
Dch nhy gm arabic 25% 20 g
Siro cam 20 g
Nc ct v. 100 gml
Potio gm thng dng lm cht dn cho cc potio c dc cht rn
khng tan trong nc.

5.3.3. Potio c cn thuc

A ntipyrin 2g
Cn aconit Hai mi lm git
Siro hoa cam 30 g
Nc ct v. 150 ml

93
 Cn 30 g siro hoa cam vo chai. Dng ng m git hp thc, nh vo chai
25 git cn aconit. Lc trn. Ho tan ring antipyrin trong nc. Lc dung chch
antipirin vo chai. Trn u.

5.3.4. Potio c cao thuc

Cao mm canhkina 2g
Cn qu 10 g
Siro v cam ng 30 g
Nc ct v. 150 ml
Ly mt na lng siro v cam ng, un nng ho tan cao mm canhkina.
Trn cn qu vo lng siro cn li. Hp hai siro vi nhau, trn u ri thm
nc va 150 ml. trn h ta cc alcaloid trong cao canhkina nn th ay nc
ct bng dung dch nhy gm arabic 5%.

5.3.5. Potio c tinh du

Calci gluconat 10 g
N atri benzoat 5g
Tinh du khuynh dip 56 git
Siro codein 30 g
Siro n 20 g
Nc ct v. 150 gml
Mun phn tn u lng tinh du khuynh dip c trong n, phi nghin
tin h du vi mt t ng. Calci gluconat t tan trong nc lnh, c n ch tng
k gia calci gluconat v n a tri benzoat to calci benzoat k t ta.
C th iu ch n ny theo cch sau:
Tn mn mt t ng trong ci (khong 20 g), thm tin h du kh u y n h dip
nghin trn k. Trn u hn hp tinh du - ng vo siro codein v siro n.
Ho tan nng calci gluconat. Sau khi ngui, lc vo hn hp trn. K huy k.
Thm dung dch n a tri benzoat. B sung nc ct va 150 ml.

6. Elixir

6.1. nh n g h a - k thut iu c h

Elixir l nhng ch phm thuc lng, cha mt hay nhiu dc cht, thng
cha t l ln ethanol v saccharose hoc polyalcol (nh glycerin) cng m t s"
ch t ph thch hp (nh cht bo qun chng nm mc...).
Elixir thng c bo ch sao cho liu dng c tn h bng s th a cafe
(5ml). Elixir c th c iu ch di dng gi bt, cm kh trc khi s dng
mi ha tan cm hoc bt trong nc. K th u t iu ch elixir c bn ging nh

94
iu ch dung dch thuc nc, siro thuc. Do th n h phn c ethanol, glycerin,
propylen glycol nn elix c n nh v sinh kh dng tt hn, bo qun c
lu hn.

6.2. M t s v d

6.2.1. Elixir paracetamol

Cng thc: Paracetam ol 24 g
E thanol 96 100 ml
Propylen glycol 100 ml
Cn clororm 20 ml
Siro n 275 ml
C ht mu, cht lm thm v.
Glycerin v . 1000 ml
Ho tan paracetam ol vo trong hn hp ethanol, propylen glycol, cn
cloroorm, thm cht mu, cht lm thm, siro n, ri thm glycerin va .
Khuy u.

6.2.2. Elixir phenobarbitan

Cng thc: Phenobarbitan 3g

Ethanol 90 400 g
Glycerin 400 g
C ht m u, cht lm thm v.
Nc tinh khit v. 1000 ml
Ho tan phenobarbitan trong ethanol. Thm cc cht cn li ri thm nc
va , khuy u.

6.2.3. Elixir piperazin citrat

Cng thc: Piperazin c itrat 187,5 g
Glycerin 100 ml
Siro n 45 g
C ht mu, cht lm thm v.
Nc tin h khit v. 1000 ml
Ho tan piperazin c itrat trong 300ml nc, thm cc cht cn li v thm
nc va 1000 ml. Khuy u.

95
7. Dung dch cn (ethanol) thuc

7.1. nh n gh a - k thut iu c h

Dung dch cn l nhng ch phm lng dng trong hoc dng ngoi, gm c
mt hoc nhiu dc cht ho tan hon ton trong ethanol.
Dung mi iu ch dung dch cn l ethanol v cc hn hp ethanol -
nc, c th ho tan c cc cht nha, tinh du, alcaloid base, v m t s cht
hu c khc (resorcin, long no, menthol, acid salicylic...)-
tan ca cc ho cht trong ethanol ph thuc vo nng ethanol.
Thng iu ch dung dch bng cch ho tan hon ton dc ch t trong
dung mi. Cc dung dch ethanol c tnh cht cm quan, l ho tn h ring, c
trng cho cc thnh phn c trong dung dch.
kim nghim cc dung dch cn thng tin h n h nh tnh, nh lng
hot cht, xc nh hm lng ethanol v o t trng ca dung dch.

7.2. M t s v d

7.2.1. Cn iod 5% (theo DVNII)

Cng thc: Iod 5g
Kali iodid 2g
Ethanol 70 v. 100 ml
Ho tan 2g kali iodid trong 10 ml ethanol 70. Cho thm iod nghin nh,
ri thm ethanol 70 cho 100 ml. Khuy cho n khi ta n hon ton.
Dung dch trong, m u nu, mi c trng.
Ch phm phi c t n h t 70% ethanol.
Trong cng thc ny kali iodid va l cht tru n g gian ho ta n va l cht n
nh.
I2 + H20 -> HI + HOI
HI + CH3 - CH2OH -> CH3 - CH2I + H 20
HOI + CH3 - CH2OH - CH3 - CHO + H20 + HI
CH3 - CHO + HOI -> CH3 - COOH + HI
CH3- CH2OH + CH3- COOH -> CH3- CH2- ooc - CH3+ H20
Nhng phn ng ny a n s th ay i m u sc, tng acid v gim
nng iod ca ch phm . Nu trong ethanol c vt m ethanol, m ethyliodid to
th n h s gy kch ng da v nim mc. Nu trong ethanol c vt aceton, aceton s
b halogen ho to triiodoaceton CH3 - c o - CI3. C ht ny c tn h cht kch ng
nim mc.

96
 Khi c m t kali iodid, cc phn ng s xy ra nh sau:
I2 + H20 -> HI + HOI
HI + HOI + KI -> KI3 + H20
Do nng iod t do khng b bin i v ch phm khng c tnh cht
kch ng.
Bo qun cn iod trong bnh c n t thu tin h mi, ch mt.

7.2.2. Cn long no 10% (theo DVNI)

Cng thc: Long no thin nhin hay tng hp 10 g
Ethanol 90 v. 100 ml
Ho tan long no trong 80 ml ethanol. Thm ethanol va 100 ml.

7.2.3. Cn bc h
Cng thc: Tinh du bc h 20 g
Ethanol 90 v. 1000 ml
Cho tinh du bc h v ethanol 90 vo mt chai c n t kn. y n t v lc
cho tan. Dung dch trong, khng mu, c mi v bc h.

7.2.4. Cn cha hc lo, nm da

Cng thc: Acid benzoic r 50 g
Acid salicylic 50 g
Iod 25 g
Ethanol 90 v. 1000 ml
Ho tan dc cht nghin mn trong ethanol 90, khuy u.

8. Dung dch glycerin

8.1. nh n gh a - k thu t iu ch

Dung dch glycerin cn gi l thuc glycerin, l nhng ch phm lng cha

dc cht ho tan trong glycerin dng ngoi.
Thng ho tan trong glycerin nhng dc cht nh acid boric, borax, iod,
tanin v nhiu cht khc.
Glycerin c nht cao, v vy khi ho tan dc cht nn un nng nh (40 -
50C) lm gim nht ca glycerin v lm tng ta n ca dc cht. i khi
phi hp glycerin vi ethanol lm dung mi.

97
8.2. M t s v d

8.2.1.Dung dch acid boric v tanin trong glycern

Cng thc: Acid boric l,0g
Tanin 2,0g
Glycerin 20,Og
Cho acid boric v tanin vo chai c sn glycerin. un cch thu ho tan.
Acid boric tc dng vi glycerin, to thnh acid glyceroboric l mt acid m nh.

h 2- o h ho c h 2- o v
I \ I \
C H -O H + B OH C H - O - B - O H +2H20
CH2- OH ho h ,2--
c 'OH

dung dch ny kch ng nim mc, c th dng n a tri hydrocarbonat

tru n g ho acid glyceroboric. Khi trung ho, phi thm n a tri hydrocarbonat t t
trn h tro dung dch ra ngoi.

8.2.2. Dung dch glycerin - iod

Cng thc: Iod 2g
Kali iodid 4g
Nc bc h 4g
Glycerin 90 g
Ho tan kali iodid v iod trong nc bc h ri trn vi glycerin.
Dung dch trong, m u nu , snh, c mi iod v bc h.
C th pha ch dung dch glycerin - iod theo cng thc sau:
Dung dch cn iod 10% 10 g
Glycerin 90 g

8.2.3. Dung dch Bromoorm (theo DVNI)

Cng thc: Bromobrm 10 g
Glycerin 30 g
Ethanol 90 60 g
Cn vo mt bnh thu tin h c n t m i ethanol, bromoform v glycerin.
Trn u.
C ht lng khng mu, trong sut, v ngt, mi bromobrm v ethanol. D ung
dch c t trng bng 1. Mt gam ch phm cho 60 git.
Bo qun trong l mu, kn.

98
 8.2.4. Dung dch digitalin 0,1% (theo DVNI)
Cng thc: D igitalin Mi centigam
E thanol 90 46 g
Glycerin 40 g
Nc ct v. 100 ml
Ho tan digitalin trong ethanol, thm glycerin v cui cng thm nc va
lOOml.
Dung dch trong, khng mu, v ng. C h phm c t trng gn bng nc
nhng c sc cng b m t nh so vi sc cng b m t ca nc. Mt gam ch
phm cha 0,001g digitalin v cha 50 git.

8.2.5. Dung dch nh tai cloram phenicol 5% trong propylen glycol

Cng thc: Cloramphenicol 5g

Propylen glycol v. 100 ml
Clormphenicol t ta n trong nc, d tan trong propylen glycol. P ha ch dung
dch bng cch ho tan dc cht trong dung mi un nng, khuy u.

9. Dung dch du
9.1. nh ngha - k thut iu c h
Dung dch du l nhng ch phm th u c bng cch ho ta n mt hoc
nhiu dc cht trong du.
Trong bo ch ngi ta thng dng du oliu, du hng dng, Vit Nam
hay dng du lc v du th u du.
Ngi ta iu ch du lc bng cch p lnh h t lc. D u lc l cht lng
mu vng sng, c mi v v d chu. T trng ca du lc bin i trong khong
0,914 - 0,920 20c. Ch s" x phng ho : 185 - 195. Ch s acid khng qu 3. Ch
s iod 84 - 100.
Du lc c th n h phn ch yu l cc glycerid ca cc acid arachidic,
linoxeric, oleic v linoleic. D u lc t ta n trong ethanol, ta n trong ether, cloroform
v ether du ha.
Du th u du l du bo p lnh t h t cy th u du (R icinus communis.
Lin), h C sa (Euphorbiaceae)\ l cht lng trong, sng v nht, khng m u
hoc vng r t nht; v kh chu. T trng ca du th u du khong 0,953 - 0,964.
Ch s x phng ho 176 - 186. Ch s" acid khng qu 3. Ch s iod 82 - 90. Ch s
acetyl khng di 140. Du th u du ta n theo bt c t l no trong ethanol tuyt
i v trong acid acetic long. Tan trong mt th tch ethanol 95% v trong hai
th tch ethanol 90%.
Ngoi du lc, du th u du, c th dng du vng, du h n h nhn, du h t
thuic phin, du ng vt (gan c).

99
 Du c th ho tan c cc cht bo, cc tin h du, nha, alcaloid base, mt
s cht v c (phosphor, iod...)
Thng thng, dung dch du c pha ch bng cch ho ta n dc cht
trong du. Dc cht cn phi kh tr n h lm c dung dch v tr n h lm bin
i du trong khi bo qun.
tng tc ho tan, c th un nng nh du. Ho ta n nng cc ch t bay
hi (tinh du) phi tin hnh trong l n t kn.
Mun ho tan nhanh dc cht, c th dng mt dung mi tru n g gian trn
ln c vi du nh ether, cloroform, aceton... Dc cht c ho ta n trong
dung mi trung gian thch hp ri trn ln vi du, sau lm bay hi dung mi
tru n g gian bng cch hm nng.
i vi nhng cht kh tan trong du, c th dng cht tru n g gian ho tan.
Mt s alcaloid base s ho tan trong du n hanh hn nu dc ch t chuyn thnh
mui oleat.
Sau khi pha ch, c th lc dung dch du qua giy lc c l xpln v
c sy kh. tng tc lc, thng lc nng.
Tnh cht ca dung dch du ph thuc vo dc cht c trong ch phm .
Dung dch du phi khng c c mi i kht. Nu khng c bo qun
cn thn, dung dch du d b bin cht (thu phn v oxy ho) di tc dng ca
oxy trong khng kh, ca m, nh sng, vi khun. N hng sn phm phn hy
du c th gy kch ng da v lm bin cht cc dc cht c trong ch phm .
ngn nga hin tng oxy ho du, c th dng cc ch t chng oxy ho (BHA,
BHT, tocoferol).
Bo qun dung dch du trong l kh, y kn, trn h nh sng, ch kh mt.

9.2. M t s v d

9.2.1. Dung dch du long no (theo DVNI)

Cng thc: Long no thin nhin hoc tng hp 100 g
Du lc v. 1000 ml
Cho long no nghin nh v du lc vo mt bnh dung tch 1500 ml,
th n h thong khuy cho n khi tan ht. C th lm ta n n h an h bng cch un
cch thu 40c.
Ch phm m u vng, mi long no.

9.2.2. Dung dch du khuynh dip

Cng thc: Tinh du khuynh dip 2g

Du lc 98 g
Trn u. Thu c cht lng snh, m u vng nht, m i khuynh dip.

100
10. Dung dch cao phn t v dung dch keo

10.1. D ung d ch cao phn t

Dung dch cao phn t l nhng dung dch cha cht tan l cc hp cht cao
phn t, c khi lng phn t vi chc nghn n hng triu, chiu di phn t
c th bng 10 ln kch thc micell trong dng dch keo. Cc hp cht cao phn
t c th c cu trc mch thng hoc cu trc phc tp b t ng hng. Khi ho
tan trong dung mi cc cao phn t cng to h phn tn v l h ng th. Tuy
nhin cc cht cao phn t khng c kh nng i qua m ng bn thm , nhng
nng v nhit n h t nh dung dch cao phn t c th chuyn t th sol (th
dung dch cc phn t phn tn t do trong dung mi lng) sang th gel (cc phn
t an xen to m ng li nh hnh giam gi cc cht lng dung mi vo trong
cu trc mng li), th gel l th cht nh hnh khng b chy lng.
Do qu trn h ho tan cao phn t qua 3 giai on: cao phn t trng n do
solvat ho, tip tc trng n do dung mi khuch tn mt chiu vo cao phn t,
cui cng l giai on ho tan. Do k th u t pha ch dung dch cao phn t cn
c thi gian ngm trong dung mi cho trng n, sau mi ho tan.
V d:
Dung dch gelatin dc dng
Thnh p h n : G elatin dc dng 10 g
Nc ct 180 ml
Cch iu ch: Ngm gelatin trong nc cho trng n hon ton (khong 30
pht), sau un cch thu di 60c, khuy cho n khi ho tan hon ton, thu
c dung dch ng nht.
Ch n h : Dng mt tha canh trong trng hp chy m u d dy.

10.2. Dung d ch keo

Dung dch keo l h siu vi d th, trong cc phn t tp hp th n h cc
micell (tiu phn keo), c kch thc t nanom et n 0,lm icrom et. c im dung
dch keo r t khng bn vng, cn c cc cht bo v keo. Cc cht bo v keo
thng dng l cc cao phn t, trong dung dch c vai tr lm tng nht, to
lp o bo v cc h t keo, tr n h s keo t ng vn do tp hp cc micell.
V d:
Dung dch Protargon
Thnh p h n : Protargon 1g
Nc ct v. 200 ml
Protargon dng bt vng nu hoc nu khng mi, v hi ng. Protargon
l mt ch phm phc hp bc oxyd v ptrotein, trong protein ng vai tr cht
bo v keo bc oxyd. Protargon cha 8% bc. Thng pha dung dch 1% lm
thuc nh m t. dung dch 0,5% th t ra bng quang.

101
 Cch p h a ch\ Cho mt lng nc ct khong 150ml vo cc c b m t ln.
Rc nh nhng mt lp mng protargon ln b m t ca nc v yn cho n
khi protargon h t nc, trng n v ho ta n hon ton vo dung dch. Khng
nn khuy khi protargon cha tan hon ton, v s lm bt protargon dnh li
th n h cc, v trong khi vn cc c bt kh, cn tr qu trn h tan. S au khi
protargon tan hon ton khuy u, lc dung dch qua bng vo l. Ra bng vi
nc ct v b sung cho n th tch quy nh.
Dung dch protargon r t nhy cm vi nh sng. Di tc dng ca nh
sng, bc oxyd c trong protargon s b phn hu, chuyn th n h bc kim loi. Bo
qun dung dch trong l thy tinh mu.

102