PHN1: t vn

Cc dng thuc quy c thng hp th nhanh nhng thi tr nhanh, do

ngi bnh phi dng nhiu ln trong ngy nht l cc thuc c thi gian bn
hy sinh hc ngn. iu ny gy phin phc cho nhng ngi bnh phi dng
thuc thng xuyn v nhiu khi ngi bnh khng m bo c ch liu
do qun thuc, ngi dy ung thuc gia ban m
Thuc tc dng ko di ra i khc phc c nhc im ni trn ca
cc dng thuc quy c, l gim s ln dng thuc, duy tr mt nng iu
tr ca dc cht thng xuyn trong mu gip cho ngi bnh trnh c cn
t pht nguy him, mt khc hn ch c nhng tc dng ph ca thuc (do
trnh c hin tng nh - y).
Indomethacin l mt trong nhng thuc chng vim phi steroid c tc
dng gim au, chng vim c s dng rng ri trong iu tr bnh thp khp,
vim khp mn - l nhng bnh o hi phi dng thuc trong thi gian di. Tuy
nhin, indomethacin c thi gian bn hy ngn v c nhiu tc dng ph. Do ,
vic dng cc ch phm indomethacin TDKD c kh nng gii phng t t dc
cht trong khong thi gin di lm gim bt tc dng ph, trnh phin phc
cho ngi bnh .
Nghin cu cc dng thuc TDKD ni chung v cc ch phm
indomethacin TDKD ni ring l yu cu cp thit. Trn th gii nhiu cng
trnh nghin cu bo ch indomethacin tc dng ko di c nhiu ch phm
c sn xut lu hnh trn th trng [16], [19]. Chnh v vy, chng ti thc
hin ti : "Nghin cu bo ch pellet indomethacin tc dng ko di" vi
cc mc tiu sau :
1. Ch to c pellet indomethacin bng phng php bi dn trong ni
bao truyn thng.
2. Ch to c pelet indomethacin tc dng ko di bng phng php
bao pellet indomethacin vi t dc tc dng ko di. Dng phng php ti u
ho la chn cng thc mng bao thch hp.

Phn 2 : Tng quan

2.1. S lc v thuc tc dng ko di
2.1.1. Khi nim
Thuc TDKD l nhng ch phm c kh nng gii phng hot cht lin
tc theo thi gian duy tr nng thuc trong mu trong phm vi iu tr
trong khong thi gian di nhm nng cao hiu qu iu tr v gim s ln dng
thuc cho ngi bnh.
Thuc TDKD t nht phi gim c mt na s ln dng thuc cho
ngi bnh so vi dng thuc quy c [7]
2.1.2. u nhc im ca thuc tc dng ko di [6] [7]
u im :
- Duy tr c nng dc cht trong m trong phm vi iu tr, gim
c dao ng nng thuc trong mu (trnh c hin tng nh - y) do
gim c tc dng khng mong mun ca thuc.
- Gim c s ln dng thuc cho ngi bnh, gim c phin phc,
trnh qun thuc, b thuc, m bo c s tun th ca ngi bnh theo ch
liu c ch nh, do nng cao c hiu qu iu tr. c bit l
nhng ngi mc bnh mn tnh phi iu tr di ngy.
- Nng cao c sinh kh dng (SKD) ca thuc do thuc c hp th
u n hn, trit hn.
Nhc im :
- Nu c hin tng ng c, tc dng ph hay khng chu thuc th
khng phi tr ngay thuc ra khi c th c.
- Thuc TDKD l nhng dng thuc i hi k thut cao. Khi ung, qu
trnh gii phng dc cht trong ng tiu ho li ph thuc rt nhiu yu t.
Do nu c sai st trong k thut bo ch hay nhng thay i sinh hc c th
ngi bnh u c th dn n nhng tht bi trong p ng lm sng so vi
thit k ban u. Ch c mt s t dc cht c ch di dng thuc TDKD



2.1.3. Cc m hnh bo ch thuc tc dng ko di [7].
2.1.3.1. H ct (Matrix)
* Ct ho tan
* Ct n mn
* Ct tr khuch tn
* Ct trao i ion
2.1.3.2. H mng bao [7]
Nguyn tc cu to : Bao dc cht bi mt mng ho tan chm hc n
mn dn trong ng tiu ho, ng vai tr l cc hng ro lm chm s gii
phng dc cht ra khi dng thuc.
* H mng bao khuch tn ( p dng trong phn thc nghim )
+ Nguyn tc cu to : Bao dc cht bi mt mng polyme khng tan
trong dch tiu ho, ng vai tr l hng ro khuch tn kim sot tc gii
phng dc cht.
+ C ch gii phng : Dc cht gii phng khi h theo ba giai on :
* Nc t mi trng bn ngoi thm vo mng, mng ht nc v
trng n. Giai on ny cn mt thi gian tim tng, tu theo kh nng thm
mi trng ca mng.
* Ho tan dc cht trong h
* Khuch tn dc cht ra mi trng bn ngoi.
+ Tc gii phng dc cht t h ra ngoi mi trng tun theo nh
lut Fick.
( )
2 1
. . C C S
e
D
dt
dQ
=

dt
dQ
: Tc khuch tn dc cht
D : H s khuch tn
S : Din tch b mt khuch tn
e : B dy mng bao khuch tn
C
1
: Nng dc cht trong mng
C
2
: Nng dc cht ngoi mi trng ho tan
Nh vy tc gii phng dc cht khi h ph thuc vo :
- Bn cht ca dc cht
- Bn cht ca mng bao
- Din tch b mt khuch tn
- B dy mng bao
+ Nguyn liu to mng : Cc polyme khng tan trong nc : ethyl
cellulose, polyvinyl acetat, hn hp eudragit ngoi ra c th thm cht lm
do (PEG, glycerin, acid stearic ) mng b rch v. Khi cn iu chnh
tc khuch tn ca dc cht ngi ta cho vo mng cc cht tan trong nc
(CMC, bt ng, natri clorid ) khi cc cht ny ho tan s to ra cc knh
khuch tn mi, mt s cht din hot (natri lauryl sulfat) cng c cho vo
mng tng kh nng thm nc ca mng.
+ u nhc im :
u im : Ti nhng thi im ban u C
1
>> C
2
( C
1
l nng
bo ho dc cht ), do vy : const C S
e
E
dt
dQ
= ~
1
. .
Nh vy tc gii phng dc cht l tng i hng nh theo thi
gian (xp x ng hc bc 0).
Nhc im : - i hi k thut bo ch cao, mt s sai st nh trong ch
to mng c th dn n gii phng nhanh hot cht. Do nhng dc cht c
tc dng mnh, ch s iu tr thp khng nn ch di dng ny, cc cht c
phn t lng ln, dc cht t tan cng khng thch hp . Gi thnh cao[16].
2.1.3.3. H thm thu
Nguyn tc cu to : dc cht d tan trong nc c dp thnh vin sau
bao ngoi vin mt mng bn thm c ming gii phng hot cht. Khi tip
xc vi dch tiu ho, nc i qua mng bn thm ho tan t dc thm thu v
dc cht to ra mt p ut thm thu trong vin cao hn p sut bn ngoi y
dung dch dc cht i qua ming ra mi trng bn ngoi. Do h TDKD
ny cn gi l bm thu thu [7].


2.2. S lc v pellet
2.2.1. nh ngha
Pellet c to thnh do qu trnh kt t ca cc tiu phn dc cht v
cc t dc thnh cc "ht thuc nh" c dng hnh cu hoc gn nh hnh cu,
thng c ng knh t 0,25mm n 1,5mm. Tuy nhin, pellet cng c th c
kch thc ln hn hoc nh hn tu theo k thut sn xut c th [4].
Bn thn pellet khng phi l mt dng bo ch hon chnh m ch l
nhng "ch phm trung gian" c a vo nang cng hoc dp thnh vin nn.
2.2.2. u nhc im ca pellet [4]
+ u im :
- Pellet cha dc cht khi a vo vin nang, vin nn s nng cao SKD
v an ton ca thuc khi ung. V pellet d phn b u trong ung tiu ho
(do c kch thc nh) nn lm gim s dao ng trong tc hp th thuc,
cng nh nng thuc trong mu. Pellet cn lm gim s dao ng trong tc
tho rng d dy, cng nh thi gian vn chuyn thuc trong ng tiu ho.
- Da trn pellet, c th to c dng thuc TDKD gii phng dc cht
t t ng tiu ho trong khong thi gian mong mun ti v tr hp thu ti
u.
- Pellet lm cho vic thit k dng thuc c thun li hn.
- Pellet c kh nng trn chy tt do d dng thu c cc vin nn,
vin nang c ng u v khi lng v hm lng cao.
+ Nhc im :
- Qu trnh sn xut pellet thng ko di v t tin.
- Qu trnh sn xut pellet i hi phi c thit b chuyn dng mc
kh cao.
- Pellet l mt ch phm trung gian nn bt buc phi c ng vo nang
cng hoc dp thnh vin nn trc khi a n tay ngi dng.
- ng u v khi lng v hm lng dc cht trong tng n v
sn phm chu nh hng ln vo mc ng u v kch thc v t trng
pellet, st ht tnh in, trng thi b mt ca pellet (th rp, gh gh), hm
lng dc cht trong tng pellet.


2.2.3. T dc dng trong k thut bo ch pellet
Trong bo ch pellet, t dc c s dng nhm hai mc tiu :
- Lm cho vic sn xut dng thuc c thun li.
- To cho dng thuc nhng c tnh, tnh cht nh mong mun.
Nhng t dc thng dng : T dc n, t dc dnh, t dc chng
dnh v t dc trn, t dc r, cht iu chnh pH, cht din hot, cht lm
tng kh nng to cu, cht iu khin gii phng dc cht [4].
2.2.4. Cc phng php ch to pellet [4], [12]
* Phng php bi n trong ni bao
Phng php ny gm hai giai on :
+ Gy nhn : Hn hp bt kp c a vo trong ni bao ang quay.
Phn dung dch t dc dnh vo khi bt. Nhn con c hnh thnh trong qu
trnh quay ca ni bao.
+ Bi dn : nhn c cho vo trong ni ang quay, dung dch t dc
dnh c phun u khp ln trn b mt ca nhn, ngay sau bt mn s
c thm vo khi nhn thm m tren. Khi tip xc vi khng kh nng thi
lin tc vo thit b, dung mi s bay hi v cc cu ni lng s c thay th
bng cc cu ni rn. Chnh cc cu ni rn ny gip cho lp bt gn cht vo
nhn. Qu trnh c lp li lin tc cho ti khi thu c cc pellet c kch
thc mong mun.
Trong mt s trng hp c th dng nhn con c sn
u im : Khng i hi trang thit b phc tp, d p dng
Nhc im : Tn thi gian, hiu sut to pellet khng cao.
Ngoi ra cn c cc phng php khc nh
* Phun sy v phun kt t
* Phng php to ht trong thit b tng si ci tin :
* n v lm trn
* Bao lp bng dung dch hay hn dch :

2.2.5. Kim tra cht lng pellet [4]
Di y l mt s ch tiu v phng php nh gi cht lng pllet :
- S phn b kch thc ht :
+ S dng b phn tch kch thc ht
+ S dng knh hin vi quang hc
+ S dng knh hin vi in t qut
+ Dng phng php phn tch hnh nh.
- Din tch b mt ca pellet : xc nh din tch b mt ca pellet
ngi ta da vo din tch b mt ring. Din tch b mt ring l din tch b
mt tnh cho mt n v th tch hay khi lng pellet.
- xp : Dng xp k thy ngn hoc knh hin vi in t qut.
- T trng biu kin ca c pellet c xc nh bng my o t trng ht,
cn t trng thc ca pellet c xc nh bng picnomet hoc bng phng
php thay th dung mi.
- bn c hc :
+ cng : Dng my th cng
+ mi mn : Dng my xc nh mi mn hay dng cc thit b bao
nh ni bao hay my bao tng si.
2.2.6. Bao mng pellet
+ Mc ch : - Bo v v tng cng s n nh ca dc cht.
- Che du mi v kh chu ca dc cht, lm tng gi tr thng phm
ca thuc.
- Bao tan rut (i vi cc dc cht b phn hy trong mi trng acid
ca d dy hoc kch ng nim mc d dy).
- iu khin qu trnh gii phng dc cht nhm to ra cc dng thuc
TDKD. S ko di tc dng t c l do phi hp cc pellet c bao bng
cng mt polyme nhng c b dy mng bao khc nhau hoc c bao bng cc
polyme c bn cht khc nhau, do m c tc v mc gii phng dc
cht khc nhau.
+ Thnh phn mng bao : - Cc polyme to mng. Tu vo mc ch m
la chn cc polyme thch hp : EC, HPMC )
- Cht lm do : DEP,DBP, PEG, Triacetin.
- Cht chng dnh : Talc, mangegi sterat.....
- Cht lm tng kh nng thm nc ca mng bo: Tween, Na
lauryl sulphat.
2.3. Indomethacin :
2.3.1. S lc v indomethacin :
a. Cng thc, ngun gc v tnh cht l ho [8, [16]
Cng thc phn t : C
19
H
16
ClNO
4

Cng thc cu to :
H CO
3
Cl
O
O
OH
N
CH3

Khi lng phn t : 357,8
Tn khoa hc : [1-(4-clorobenzoyl) -5- methoxy-2-methylindol-3-yl]
acetic acid.
* Tnh cht l ho
Indomethacin l bt kt tinh mu trng hay ng vng, khng c mi hoc
hu nh khng mi. Nhit nng chy 153
o
- 154
o
. Khng tan trong nc,
tan trong ethanol. aceton. Vng bn trong mi trng trung tnh hay acid yu,
phn hy trong dung dch kim mnh.
Indomethacin l mt acid hu c yu.
b. Dc ng hc [14]
Indomethacin hp thu nhanh khi ung v t c nng ti a trong
mu sau khi ung khong 2h. phn b vo h tun hon, h thn kinh trung
ng v mt lng nh vo sa m. Lin kt protein huyt tng vi t l cao,
khong 99%. chuyn ho nhanh chng qua gan bng cc phn ng kh methyl,
kh alkyl. thi tr qua thn theo nc tiu di dng chuyn ho (dng
gluconid lin hp). Thi gian bn thi trung bnh : T
1/2
= 2,6 - 11,2h tr s
sinh : T
1/2
= 15h - 30h
c. Tc dng dc l v ch nh [3] [9] [15]
- Indomethacin tc dng c c trn giai on u v giai on mun
(mn tnh) ca vim, c dng ch yu lm thuc chng vim, c bit trong
vim khp xng, h khp, vim t sng cng khp, vim a khp mn tnh
tin trin, vim dy thn kinh Indomethacin c dng iu tr bnh Gout
cp.
- Cng nh cc thuc chng vim phi steroid khc, indomethacin dng
trong iu tr cc chng au nh, au va nh au mn tnh sau phu thut, au
do vim (au khp, au c, au rng), au bng kinh, au u, k c au na
u
d. Liu lng, cch dng [3] [9] [15]
Lc u ung 25-50 mg , 2-3 ln/ ngy. Ung khi n hoc ngay sau khi
n, Nu bnh nhn dung np tt, hng tun tng thm liu 25-50mg ti 150-200
mg mi ngy.
e. Tc dng khng mong mun v chng ch nh [3] [9] [15]
liu iu tr, indomethacin gy tc dng ph t 35-50% bnh nhn do c
ch cyclooxygennase-1, ch yu ng tiu ho nh gy ri lon tiu ho, gy
lot d dy - ta trng v h thn kinh trung ng gy au u, chng mt, o
gic. Ngoi ra thuc cn gy c vi thn, lm tng thi gian chy mu, ko di
thi gian mang thai v gy kh .
Chng ch nh i vi nhng bnh nhn lot d dy - t trng, ngi b
bnh thn suy t bo gan nng, tr di 2 tui , ph n c thai v cho con b..
2.4. Mt s phng php ti u ho cng thc bo ch
K thut ti u ho s dng my tnh c chng t l phng php
c hiu qu la chn cng thc bo ch ti u. Di y, hai phng php
ti u ho thng dng s c trnh by .
2.4.1. Ti u ho da trn hm mc tiu bc 2 [2][14]
Phng php ti u ny gm nhng bc c bn sau :
- Xc nh cc yu t u ra (bin ph thuc) cn ti u ho
- Xc nh cc yu t u vo (bin c lp) nh hng n cc yu t
u ra.
- Thit k cc th nghim nhm phn tch nh hng ca cc bin c lp
ln cc bin ph thuc.
- Tin hnh cc th nghim theo cc thng s thit k.
- T cc kt qu th nghim, xy dng cc phng trnh hi quy dng a
thc bc hai biu din quan h gia cc bin ph thuc v cc bin c lp.
Nhng phng trnh ny cho php d on gi tr ca cc bin ph thuc khi
bit gi tr ca cc bin c lp m khng cn lm thm th nghim.
- Ti u ho cc bin ph thuc da trn cc phng trnh hi quy (hm
mc tiu bc hai) tm cc gi tr ti u ca cc bin c lp.
- Lm th nghim theo cc gi tr ti u ca cc bin c lp va tm c
kim tra v iu chnh nu cn.
Nh vy, vn ti u c m t mt cch ton hc l tm cc tiu
(hoc cc i) ca hm mc tiu F(x) vi nhng rng buc dng phng trnh
hoc bt phng trnh :
G
i
(X) > 0 i = 1, 2, 3 m (1) (rng buc dng bt phng trnh)
H
j
(X) = 0 j = 1, 2, 3,,,n (2) ( rng buc dng phng trnh)
Thng thng, rt kh gii quyt vn ti u c rng buc m khng
thay i v mt ton hc, v vy vn ti u c rng buc c chuyn sang
ti u khng rng buc bng cch thm cc hm s b nh sau :
( ) | | ( ) | |

=

+ u + =
n
j
j i
m
i
i
X H r X G r x F r X T
1
2 1 2
1
1
) ( ) , ( (3)
Trong : Khi G
i
(X) < 0 , u
i
= 1
Khi G
i
(X) > 0 , u
i
= 0
Hm T(X, r) l hm mc tiu khng rng buc chuyn i, trong r
l h s nghch o ca T(X, r). S hng th 2 v 3 trong phng trnh 3 ng
vai tr l hm s b v gi tr ca chng s tng mnh khi gi tr ca G
i
(X) m
hoc gi tr ca Hj(X) lch khi khng vi r l mt s dng nh.


2.4.2. Ti u ho da trn mng thn kinh nhn to [2], [13]
S vn hnh ca mng thn kinh nhn to (Artificial neural network -
ANN) da trn s m phng qa trnh thn kinh sinh hc din ra trong b no
ngi. S vn hnh ny c th xc nh mi tng quan gia nhng cp d liu
vo v ra v c th c coi l k thut nhn dng mu. ANN rt hu ch i
vi nhng m hnh h thng m mi quan h gia cc bin c lp v bin
ph thuc l rt phc tp (phng trnh hi quy dng a thc bc hai khng th
m t y mi quan h ny ) [2].

Y1 Y2
X X1 2
Yj Ym
Xi Xn
L p ra
L p n
L p vo



Hnh 1. Cu trc in hnh ca ANN

Hnh 1.. M t cu trc in hnh ca ANN. ANN c mt lp vo, mt
hay nhiu lp n v mt lp ra. Mi lp c mt hay nhiu n v ng vai tr
nh cc neuron. Cc n v cc lp gn nhau c kt ni hon ton vi nhau
bng nhng ng kt ni ng vai tr nh cc synap. Cng lin kt gia
hai n v c gi l "khi lng". S lng ca lp n hay s lng cc n
v trong lp n c xc nh tu . mi lp n v lp ra cc n v x l tp
hp cc thng tin vo t cc lp pha trc v sau p dng hm sigma tnh
ton gi tr ra cho cc lp tip theo theo phng trnh :

i j
X i W Y

= (4)

( ) { } Y
Y F
o +
=
exp 1
1
) ( (5)
Trong W
ij
l khi lng ca mi lin kt gia n v i trong lp hin
ti v n v j trong lp k tip v X l gi tr ra t lp trc . F(Y) c tnh
cho lp tip theo nh l gi tr ra.o l tham s lin quan ti dng ca hm sigma.
Tnh phi tuyn tnh ca hm sigma c tng ln khi gi tro tng. ANN "hc"
mi quan h phi tuyn xp x nh mt qu trnh gi l "hun luyn" bng cch
bin i Wij.
1.3.3. So snh th gii phng dc cht
C rt nhiu phng php c s dng nh gi xem hai th gii
phng dc cht ca hai ch phm l ging nhau hay khc nhau trong thng
dng hn c l test f
2
c quy nh bi c quan qun l dc phm v thc
phm M FDA [10]. [11]
f
2
: Ch s th hin s ging nhau ca hai ng cong ho tan (similarity
factor) c tnh bi cng thc :
( ) ) 6 ( 100 . .
1
1 lg 50
5 , 0
2
1
2

+ =

=

n
i
t t
T R
n
f
n : s im ly mu
R
t
: Phn trm dc cht ha tan ti thi im t ca mu i chiu.
T
t
: Phn trm dc cht ho tan ti thi im t ca mu th
Tiu chun t ra : hai th c coi nh tng t nhau nu f
2
nm
trong khong t 50-100, gi tr f
2
cng ln th hai th cng ging nhau. Mt
s nghin cu s dng f
2
nh mt thng s ti u ho (t ra bi ton tm f
2

max) [10], [11].







Nguyn vt liu - Phng php nghin cu

3.1. Nguyn vt liu v phng tin nghin cu

3.1.1. Nguyn vt liu

Nguyn liu Ngun gc Nguyn liu Ngun gc
Indomethacin Shanghai
Meheco
Trung Quc
Ethyl
cellulose
AG, Chem Fabuk
Ch-9470 buchs -
c
Avicel PH
102
i Loan Ethyl
cellulose
Fluka AG, Chem
Fabuk Ch-9470
Buchs - c
Lactose Anh Titan dioxyd Php
Polyvinyl
Pyrolidon
M Tween 80 Trung Quc
Ethanol Cng ty ho cht
c Giang
Diethyl
phtalat
B mn ho dc
- i hc Dc
H Ni
Talc Php


3.1.2. Phng tin nghin cu
- My o trc nghim ho tan Erweka DT (c)
- My o quang ph hp th t ngoi UV - Vis Heiosy (Anh)
- My o tc chy ca ht v bt Erweka GWF (c)
- Bt ry phn tch kch thc ht Erweka (c)
- My o th tch biu kin ca ht v bt Erweka SVM (c )
- My xc nh m Chyo IB - 30 (Nht)
- My xc nh mi mn Erweka TA 10 (c)
- Ni bao Erweka (c) c lp sng phung v h thng ht bi.
- My khuy a
3.2. Phng php nghin cu
3.2.1. Ch to pellet indomethacin:
Pellet indomethacin c ch to bng phng php bi dn trong ni
bao. Phng php ny gm 2 giai on :
- Gy nhn
- Bi dn
3.2.2. Ch to pellet indomethacin tc dng ko di;
Pellet c kch thc thch hp (1-1,25mm) c cho vo ni bao, quay
ni bao. Phun dch bao (c cha t dc TDKD) vo khi pellet, ng thi thi
gi nng lin tc vo ni. Sau khi phun ht dch bao vn th gi nng v cho
pellet quay trong ni bao 15 pht, sy pellet 50
o
C trong 3 gi n nh mng
bao [4].
3.2.3. Kho st mt s c tnh ca pellet, pellet tc dng ko di [4]
* o tc chy : Tc chy ca pellet v pellet tc dng ko di c
o trn my o Eweka GWF vi ng knh l phu 1,3cm.
Tc chyc tnh theo cng thc
v = tg
v : Tc chy (g/s)
: gc gi ng thng biu din s ph thuc ca khi lng pellet
chy theo thi gian v trc honh (trc thi gian).
* o khi lng ring biu kin : c tin hnh trn my o Erweka
SVM. Khi lng ring biu kin c tnh theo cng thc :
d = m/V
d : Khi lng ring biu kin (g/ml)
m : Khi lng pellet hoc pellet TDKD (g)
V : Th tch biu kin ca pellet (ml).
* Xc nh mi mn (p dng cho pellet cha bao) : tin hnh trn
my o Erweka TA 10. mi mn c tnh theo cng thc :
100 . (%)
1
2 1
m
m m
x

=
Trong :
s : mi mn
m
1
: Khi lng pellet trc khi b mi mn
m
2
: khi lng pellet sau khi b mi mn.
* Xc nh m : Tin hnh trn my xc nh m Chyo IB-30.
3.2.4. nh lngINDOMETHACIN trong pellet hoc pellet tc dng ko di
nh lng bng phng php o quang (tham kho tiu chun vin ca
DVN tp 3 vUSP24 )
3.2.5. Phng php bo ch vin nang Indomethacin :
Pellet Inolomethacin TDKD c ng vo nang cng bng thit b ng
nang th cng.
3.2.6. Phng php nh gi tc gii phng Indomethacin t pellet,
vin nang
Dng my trc nghim ho tan theo quy trnh ca USP 24.
3.2.7. Phng php so snh cc ng cong ho tan
Hai ng cong ho tan c so snh vi nhau theo phng php c lp
vi m hnh c quy nh bi c quan qun l dc phm v thc phm M
(FDA) [10], [11].
Phng php ny s dng ch s f
2
(similarity factor)
( )

+ =

=

100 .
1
1 lg . 50
5 , 0
1
2
2
n
t
t t
T R
n
f
n : s im ly mu
Rt : Phn trm INC h tan ti thi im t ca mu i chiu
t
t
: Phn trm INC ho tan ti thi im t ca mu th.
Tiu chun t ra : 2 ng cong c coi l ging nhau nu f
2
nm trong
khong 50-100.
3.2.8. Thit k th nghim v ti u ho cng thc mng bao
+ Da trn hm mc tiu bc 2
+ Da trn mng thn kinh nhn to :

d kin kt qu t c

1. Xc nh c cng thc bao ch pellet indomethacin v bao ch c
pellet indomethacin bng ni bao truyn thng t c yu cu mng
bao kim sot gii phng.
2. Kho st nh hng ca cc yu t c trong thnh phn mng bao ti tc
gii phng indomethacin khi pellet tc dng ko di.
3. s dng phng php ti u ho la chn c cng thc bo ch
mng kim sot gi phng bao ch vin nng indomethacin c m hnh
gii phng gn ging vin i chiu.