TM QUAN TRNG KH NNG T CA T DC TRN C TNH

CA VIN NN C CHUN B BI S TO HT KH KCH HOT

M (MADG)

Hiroshi Takasakiaa, Etsuo Yonemochid,*, Roman Messerschmidc, Masanori

Itoa,Koichi Wadaa, Katsuhide Teradab

a) Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima Minamimachi

Chuo-ku Kobe Hyogo, 650-0047, Japan

b) Faculty of Pharmaceutical Science, Toho University, 2-2-1 Miyama

Funabashi Chiba, 274-8510, Japan

c) Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr. 65, 88400
Biberach a.d. Riss, Germany

d) Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-

ku, 142-8501 Tokyo, Japana

Thng tin bi bo

Lch s bi bo

nhn ngy 16 thng 5 nm 2013

Nhn c dng sa i ngy 30 thng 7 nm 2013

c chp nhn vo ngy 15 thng 8 nm 2013

C sn trc tuyn 27 Thng 8 2013

T kho:

m kh c kch hot

Cht hp th m

Kh nng t
TM TT

i vi ht kh c kch hot m (MADG), cellulose vi tinh th (MCC) hoc silic

dioxide c xut cho giai on hp th m. Mc tiu ca nghin cu ny l
nh gi s ph hp ca cc s la chn t dc nh l cht ht m i vi c ch
phn hy ng sa trn cng thc thuc . Bn cnh loi MCC m cao v
m thp, cc cht b sung ca MAMS,bt tinh bt (S1500), crospovidon
(Kollidon CL) v carmellose calcium (ECG 505) c nh gi. S nghin ct
ht cao (HSG) c hng dn nh mt quy trnh tham kho. Thi gian tan r
tng th ca tt c vin nn do MADG sn xut nhanh hn ng k, trong khi
cng v s thay i khi lng bng hoc cao hn so vi quy trnh HSG. Kh
nng m bt ca cc cht ht m khc nhau c xc nh l mt gii php
chnh nhanh chng tan r, trong khi rng ca vin thuc ch nh hng n
cng cn t ca vin nn.

I. Gii thiu

nghin ct cao (HSG) l mt trong nhng quy trnh ph bin nht trong
ngnh dc phm v n cung cp cc ht nh d chy c cha thnh phn hot
cht phn b u. N c kh nng che giu nhng c tnh gy bt li v cng
nh lm cn bng cc bin i c th xy ra trong qu trnh pht trin sn phm
thuc hoc bng cch tm ngun cung cp hot cht t cc nh cung cp khc
nhau. T quan im ch bin, HSG km hn quy trnh ch to ht nn trc tip
kh v cn thm mt bc sy kh sau giai on kt t trong cc thit b ring
bit, chng hn nh khay sy hoc my sy tng si. khc phc iu ny, my
to ht mt ni nung lm kh cc ht bng l vi sng hoc bng my sy chn
khng ( kh t h tr ) sau khi ng t. Ngoi vic gia tng ng sut nhit ca
sn phm do nng lng vi sng, s hnh thnh cc adhesion trn cc thnh ht
hoc. S ph v ht do lc c hc l nhng thch thc trong qu trnh sy.

Do , ht kh c kch hot m (MADG) c th a ra mt thay th th v

kt hp cc li ch ca HSG ng thi c th trnh c cc vn lin quan
n sy c m t trn. Cng ngh ny ban u c m t bi (Ullah v cng
s) nm 1987. Ton b qu trnh l tng c th c thc hin trong qu trnh
nghin ct thng thng, kt qu t vic trn trc cc thnh phn cho qu trnh
nghin trn u cui cng ca cht h tr chc nng nh cht lm phn r
hoc bi trn trc qu trnh nn. Do , vic chuyn cc sn phm trung gian
trong qu trnh x l sang cc thit b khc c th khng cn thit, v vy tit
kim c thi gian v chi ph. Cui cng, do cc bc chuyn l ngun ch yu
nm ngoi mong mun, MADG l qu trnh to ht l tng cho vic sn xut cc
dng bo ch liu thuc dng rn t cc hp cht c hiu lc cao.

Qu trnh MADG c th c chia thnh hai giai on khc nhau: giai

on tp trung v giai on hp th m (Ullah v cng s, 2009b). API ban
u, cc cht ha tan trong nc v cht kt dnh c trn sn trong my to ht
v cht kt dnh c kch hot bi mt lng nc nh to thnh cc ht.
MADG thng yu cu lng gim ng k cht lng to ht so vi mt quy trnh
HSG thng thng (1-4% (m / m)) ca khi lng ht to c(Ullahet al.,
2009b). Trong giai on hp th, m trong cc ht gim v phn phi cho
ton b hn hp bng cch thm mt thnh phn khng tan trong nc nh mt
cht bt hp th.

Hu ht cc nghin cu u cho rng cellulose vi tinh th v cc lp silic

oxit keo hoc crospovidone l cc cht hp th nc tt cho MADG (Chen v
cng s, 1990, Christensen v cng s, 1994. Railkar v Schwartz, 2001a, b,
Ullah v cng s, 2009a, B). Ullah cho bit Avicel PH 200LM (loi m thp:
nc <1,5% (m / m)) v Aerosil 300, ngoi chc nng chnh ca chng trong
cng thc vin thuc, rt thch hp lm cht hp th cho MADG v chng l cc
t dc c hm lng nc rt thp (Ullah v cng s, 2009a, b). Christensen
nh gi tinh bt nguyn cht v cc hn hp ca tinh bt v cellulose vi tinh
th nh l cht hp th (Christensen v cng s, 1994). Mc d tinh bt t nhin
c tm thy h tr tnh ng nht v s phn hy nhanh ca vin thuc,
cng gim. y c th l mt du hiu bin dng n hi c a ra bi bn
cht t nhin sau chu k nn.

Mc ch ca nghin cu ny l im quy chun cc cht hp th m

thng thng cho MADG lin quan n tnh cht ca ht v cc tnh cht ca
vin thuc. Cc cht thay th mi c nh gi: tinh bt c tin gelatin
ho vi c tnh bt tt hn so vi tinh bt t nhin v cht m v c thng
c s dng Nht Bn phun magnesium aluminometasilicate kh c kh nng
hp th cht lng cao (Hentzschel, 2011). Cht phn hy (crospovidone,
canarmose calci) cng c nh gi. Hn na, l do phn hy nhanh cc vin
nn do MADG sn xut, kt hp vi nng sut cng tuyt vi c iu tra.
m t ca cht hp th m bng nc c o n tnh cht ha l tng ng
vi thi gian tan r ca cc vin thuc. HSG c tin hnh so snh.

2. Vt liu v phng php

Cc l 250 g c ch bin trong mt my nghin ht ln (Diosna P1 / 6,

Diosna) c trang b mt b to ht 1 L. Cc thng s ch bin c gi khng
i trong sut qu trnh kt t (1 pht) v tp trung (3 pht) : tuabin khuy 500
rpm, my bm 1200 rpm. Cc hn hp hon tt c nn thnh tm phng c b
mt c ng knh 8 mm v khi lng 200 mg trn my p lch tm (Korsch
EK0, Korsch) vi cc lc nn khc nhau l 2,5 kN; 5,0 kN; 7,5 kN; 10,0 kN v
15,0 kN.

2.1. HSG gin on

Cht lactose monohydrat tinh khit (Granulac 200, Meggle) v cellulose

vi tinh th (Avicel PH101, FMC) lm cht n cha mt lng nh cht st oxit
(Univar Ltd.) kim tra s ng nht v hn hp ban u c trn vi cht kt
dnh. Polyvidone (Povidone K25 , BASF) v c to ht bng cch thm 20% (m
/ m) nc thng qua mt my bm nhu ng. Povidone K12 c s dng
trong mt th nghim trc. Tuy nhin, vic s dng lp Polyvidone c nht
thp khng mang li kt qu ht hon chnh. Cc ht t c tri qua mn chn
2 mm, sy kh trong my sy khay (my sy khay 10ES, Nagato) 60C trong
50 pht v sng bng my sng sng hnh nn (sng sng 1,0 mm, Quadro
Comil U5, Powrex). Cc thnh phn ca crospovidon disin-tegrant (Kollidon CL,
BASF) v sng trc cht bi trn magnesium stearate (Magnesium stearate
vegetable, Faci) cui cng c trn vi cc ht nh trong 5 pht (my trn
Turbla, T2F, Shinmaru Enterprises).

2.2. M MADG

Cht lactose monohydrat loi mn (Granulac 200, Meggle) cha mt lng

nh cht st oxit (Univar Ltd.) c trn vi cht kt dnh Polyvidone
(Povidone K12, BASF) v c to ht bng cch phun nc 2% (m / m) trong 15
giy (ng knh vi phun 0,3 mm, p sut khng kh phun 2,5 bar) vo trong
b to ht. Trong mt th nghim trc, lp Polyvidone (Povidone K25) c
nht cao khng tch t bng cch thm vo lng nc thp ny. Do ,
loi nht thp c chn, theo phn loi (Ullah v cng s, 2009a, b).
Trong giai on hp th 2 pht, cc cht hp th m theo sau c thm vo
trong khi my bm dng li: cellulose vi tinh th (Avicel PH102 & Avicel PH200
LM, FMC) cng vi keo silic dioxide (Aerosil 200, Degussa), magi
aluminometasilicate (MAMS, Neoallumin S, Tomita), tinh bt c tin
gelatin ho (Starch 1500, Colorcon), crospovidone (Kollidon CL, BASF) hoc
canxi carmellose (ECG 505, Gotokuchemical).

Theo cc cng thc c m t trc y (Ullah v cng s, 2009a, b)

Cellulose vi tinh th nh l cht hp th m khong mt phn t hn hp to
ht nh, trong khi n c tm thy rng cc thnh phn ca cc cht hp th
m khc c th c gim ng k m khng thay i s lng ln (v d kch
thc ht hoc m cn st li) ca kt qu to ht (Bng 1 )

Cui cng phn hy crospovidon (Kollidon CL, BASF) v magnesium

stearat bi trn tinh th c trn trc tip vo my to ht trong 1,5 min
pht v 0,5 pht tc vng tua gim 250 rpm.

2.3. Phn b kch thc ht

S phn b cc kch thc ht ca hn hp hon tt c o bng my sng

phn tch(Robot Shifter RPS-95, Seishin) gm c cc tm sau: 355 m, 250 m,
180 m, 125 m, 90 m, 75 m. M, 63 m thi gian sng lc 5 pht mc rung
4 v xung khong 1 giy. Ni suy ra nt cho mt d10, d50 v d90 v c xc
nh bng cch s dng phn mm Easysieve (Retsch). Khong thi gian nh
gi cht lng phn phi c tnh nh sau (d90 - d10) / d50.

2.4. Mt ln v mt khai thc

Mt khi lng v mt pha trn ca hn hp hon tt c xc

nh trong mt cc mu 100 mL trn h thng o lng bt (My kim tra bt PT-
R, Hosokawa micron) bng cch s dng 180 vi. T l Hausner nh l mt i
din cho tnh lu ng c tnh nh l t l ca mt khai thc v mt
ln: ( c khai thc / s lng ln). Kh nng chy c phn loi theo tiu
chun Hoa K v Phar-macopedial ca cc tiu chun xut sc (1,00-1,11), tt
(1,12-1,18), cng bng (1,19-1,25) n kh (1,26-1,34).

2.5. Mt mt khi sy kh

Thit hi do sy (LOD) ca hn hp cui cng c o bng cn bng m

(HG63-P, Mettler Toledo) 105 C trong 10 pht. Cc nh gi c tin hnh
trn cc mu pha trn cui cng 3 cc v tr khc nhau ca khi nh gi
vng qu m t.

2.6. cng ca tablet v dy

cng ca vin nn v chiu cao ca vin thuc c o bng my o

cng ca my tnh bng (TBH425, ERWEKA). Cng ko c tnh nh 2 F /
(* D * T): trong F l cng, v o dn truyn D v T v dy ca vin.

2.7. Thi gian tan r ca my tnh bng

Thi gian tan r ca vin thuc c o 37C s dng my th phn hu

(NT-400, Toyama) 30 chu k / pht. Khng b sung thm.

2.8. rng ca vin thuc

rng ca vin thuc () c tnh bng cch s dng cng thc

True
= 1-(m/ * V),

True
Trong m v V l khi lng v th tch ca cc bng. Mt tht ( )
c o bng mt thit b o rung bng mng thy ngn (Amico).

Bng 1 Cng thc c s dng trong th nghim MADG (% khi lng

vin).
Giai on X l (LPRa) HSG MAD
x l (20%) G (2%)
1 Granulac 200 65.0 64.5 64.5 79.4 79.4 85.4 85.4
Oxit St 0.1 0.1 0.1 0.1 0.1 0.1 0.1
Povidone K25 5.0 _ 5.0 _ _ _ _
Povidone K12 _ 5.0 _ 5.0 5.0 5.0 5.0
Avicel PH101 26.4 _ _ _ _ _ _

2 Avicel PH 200LMb _ 26.4 _ _ _ _ _

Avicel _ _ 26.4 _ _ _ _
PH102SCGb _ 0.5 0.5 _ _ _ _
Aerosilb _ _ _ 12.0 _ _ _
MAMSb _ _ _ _ 12.0 _ _
S1500b _ _ _ _ _ 6.0 _
Crosspbovidoneb _ _ _ _ _ _ 6.0
ECG505b
3 Crosspovidone 2.5 2.5 2.5 2.5 2.5 2.5 2.5
Magnesium 1.0 1.0 1.0 1.0 1.0 1.0 1.0
stearate
Tng 100.0 100.0 100. 100. 100. 100. 100.0
cng 0 0 0 0

1= S kt tinh/Khi lng ln; 2= m hp th; 3= ng dn chnh v

pha trn cui
a
= T l cht lng / bt

b
= Cht hp th m

2.9. Kh nng thm nc v cht ht m

o lng bn c thc hin 25 C vi cng b mt c cn

bng (K21, KRUSS GmbH), trong o khi lng ca cht lng hp ph
so vi thi gian. kim tra cht hp th m, mi cht hp th c
ng gi trong mt ng khng g. th nghim vin, vin thuc c a
trc tip vo ng khng r. ng khng g c cha cht ht m hoc vin
thuc c h xung nc v lu thi gian c thc hin khi nc
tip xc vi ng khng g. Trng lng nc xm nhp vo t dc hoc
vin thuc c ghi li theo thi gian. S liu c thu thp mi 20 ms.
nh gi kh nng t, t ln u v mao dn t (g2 / s) c tnh
ton da trn cu hnh.

Mi quan h gia thi gian v trng lng c tnh bng phng

trnh Washburn, trong thi gian t l thun vi bnh phng ca trng
lng (phng trnh (1)). Phng trnh (1) c chuyn i thnh
phng trnh (3) thng qua phng trnh (2). bnh phng ca xp nh
hng n bnh phng trng lng.

2 L . 2 . c .cos
w = .t (1)

L : Nng lng t do trn b mt ca dung dch (N/m)

: Mt cht lng (kg/m3)

: Gc tip xc ()

: nht ca cht lng (Pas)

c : Hng s c (m5)

r : Bn knh mao dn (m)

n : S mao mch

R : Bn knh (m)

3. Kt qu v tho lun

3.1. Quy trnh MADG v cc c tnh ca ht

 Bng 1 cho thy cc cng thc c s dng trong nghin cu ny.
Cc ht cho tt c cc cng thc c tt. Khng c s kt dnh tng
hay s hnh thnh khi u ln. c tnh ca ht c th hin trong bng 2.
Kch thc ht trung bnh ca m (68-107 m) nh hn so vi kch thc ht
ca HSG (119 m). L do c th l do lng nc thp hn c s dng cho
MADG so vi HSG (Christensen v cng s, 1994). V l do ti sao cc
khong phn b kch thc ht bng cch thm S1500, Kollidon CL v
ECG 505 rng hn so vi cc cht hp th nc khc, hoc l lng cht
hp th c th qu cao hoc lng cht kt dnh c th qu thp i vi
cc cng thc ny .

Cc h s Hausner ca ht MADG c chp nhn (1,19-1,32), v

do s khc bit khi lng ca vin thuc trong qu trnh nn (0,28-
0,41%) l tng ng, nh i vi cc ht c sn xut bi HSG (0,41%).
Cc kt qu tng t c bo co bi cc nh nghin cu khc
(Christensen v cng s, 1994), kch thc ht nh ca cc ht c to ra
dng nh khng c tc ng ln n s thay i khi lng ca vin
thuc.

Do t l ca ht Hausner c sn xut bi Avicel PH 102 (1,25) cao

hn ht to bi Acicel PH200 LM (1,19), kch thc ht ban u c th c
nh hng n h s Hausner ca hn hp cui cng. Mc d vy, s thay
i khi lng vin thuc ca cc cng thc c cha Avicel PH102 l chp
nhn c (0.37%).

LOD ca hn hp cui cng t cc ht c sn xut bi Avicel PH

102 (3,39%) tng ng vi sn phm c sn xut t Avicel PH200 LM
(3,40%), cho thy c hai cng thc c cn bng vi mi trng xung
quanh trong sut qu trnh.

3.2. Sc cng
nh hng ca cht hp th m n bn ko c kho st .
Hnh. 1 cho thy sc cng ca vin nn nh l mt chc nng ca lc nn.
Phn ln cht hp th m trong cc cng thc c bn ko . bn
ko ca vin nn cha Avicel PH200LM (3,21 MPa: lc nn 10 kN), Avicel
PH102 (3,53 MPa: lc nn 10 kN)
 Hnh. 1.Sc p nn v sc cng ca vin nn (Mean n = 10, SD)

Hnh. 2. Thi gian tan r so vi bn ko ca vin nn (Mean n = 6,

min / max).

v MAMS (3,70 MPa: lc nn 10 kN) cao hn ng k so vi cc vin nn

sn xut bi HSG (1,84 MPa: lc nn 10 kN). bn ko ca cc vin nn
c cha ECG 505 (2,35 MPa: lc nn 10 kN) v Kollidon CL (1,71 MPa:
lc nn 10 kN) cho thy nn gn nh tng ng vi vin nn sn xut
bi HSG, trong khi cc vin nn c cha S1500 (1,49 MPa: lc nn 10
kN) thp hn HSG. MAMS thun khit cho thy nn cao do din tch b
mt ln (Hentzschel v cng s, 2012). V MCC tinh khit c th t c
 nn cao lc nn thp (Jivraj et al., 2000). Kh nng nn nh gn ca
MAMS thun khit, Avicel 200LMand Avicel PH 102 c th nh hng
n s gia tng sc cng ca my tnh bng.

Avicel PH102 cao hn ng k khi chun b theo quy trnh MADG so

vi vin nn c sn xut bi HSG. N ch ra rng tnh nn ca MCC
bng ht t gim do gim mi mn ban u ca MCC (Badawy v cng
s, 2006; Staniforth Et al, 1988). Do , l do c th l do s mt nn
MCC ny trong qu trnh HSG.

Hnh. 3. Tnh nng hp th nc (Mean n = 3, SD).

 Bng 2 : c im ca ht v bin th khi lng ca vin thuc

3.3. Thi k tan r

nh hng ca cht hp th m vo thi gian tan r c iu

tra. Hnh. 2 cho thy thi gian tan r ca vin nn nh l mt chc nng
ca bn ko. Thi gian tan r ca vin thuc do HSG sn xut c ko
di vi cng ko cng. V d, thi gian tan r ca vin nn c sn
xut bi HSG hn 5 pht 2,86 MPa. Ngc li, thi gian tan r ca
vin thuc do MADG sn xut nhanh hn ng k so vi vin nn sn xut
bi HSG. c bit, cc vin nn c cha Avicel PH 200LM, Avicel PH102
v MAMS phn hy nhanh hn cc vin nn cha ECG505 v S1500.
Nhng kt qu ny gi rng cc c tnh hp th m c th c tc ng
n thi gian phn hu.

3.4. nh gi s khc bit v thi gian phn hu ca thuc gia HSG

v MADG

S khc bit v thi gian phn hu (HSG: 61 giy, Avicel PH102: 18

giy) c quan st thy gia cc vin nn sn xut bi HSG v MADG c
cng thc tng ng v bn ko (HSG: 1,84 MPa, Avicel PH102: 1,72
MPa). Khi s tan r ca thuc vin c lin quan n kh nng t v xp
(Fukami v cng s, 2006), tnh cht t v tnh xp ca vin thuc c
iu tra.

Hnh. 3 cho thy cu hnh hp th nc ca vin nn. Cc hnh vi t

c chia thnh hai hin tng: t ban u v t. S t ban u c
nh ngha l lm t b mt ca lp thuc vin. Sau , nc xm nhp
vo vin thuc, c nh ngha l lm t mao mch. Vic t ln u tin
c tnh bng cch s dng hi quy tuyn tnh 5 im, trong khi t do
mao mch c tnh bng cch s dng hi quy tuyn tnh trng thi cn
bng. Hnh. 4 cho thy t ban u v t cho cc vin nn sn xut t
HSG v MADG. Hnh. 5 cho thy rng ca vin nn.

Kt qu l s t ban u khng cho thy bt k s khc bit no (p>

0,05), trong khi s t ca mao mch cho thy s khc bit thng k gia
cc vin nn sn xut bi HSG v MADG (p <0,05). V rng ca vin
thuc cho thy s khc bit thng k gia cc vin nn c sn xut bi
HSG v MADG (p <0,05).

Cc hnh vung ca rng sn xut bi MADG cho thy tng 24%

so vi rng ca HSG, c th l do hnh vung trng lng (hp th nc)
tng ln. Trng lng ( hp th nc) do MADG sn xut cho thy tng
47% so vi trng lng do HSG sn xut 20 giy. Vic t mao mch c
th c tc ng n 23% cn li. Cc kt qu ny cho thy rng ca vin
thuc (ng gp c tnh 24%) v s t ca mao mch cho my tnh bng
(ng gp c tnh 23%) c th nh hng n thi gian tan v ca vin
thuc do MADG sn xut.
 Hnh. 4. Lm t ban u v mao mch ca vin nn c sn xut bi
HSG v MADG Wetting (Mean n = 3, SD).

Qu trnh ht t gim rng ca cellulose vi tinh th. S gim ny

l do s gim khi lng l rng gia cc cu trc nh hn (Badawy v
cng s, 2006). S gim mi mn ca MCC c th c tc ng ng k
n s t v m hi ca mao mch MCC, dn n s thm thu nc thp
vo vin.
 Hnh. 5. mn ca vin nn c sn xut bi HSG v MADG Porosity
(Mean n = 10, SD)

xc nh thi gian tan r ca vin nn sn xut bng MADG c s

khc bit ng k, nh hng ca kh nng cha nc ca cht ht m khc
nhau trong thi gian tan r c kho st.Hnh 6 cho thy m t
ban u v s lm t mao dn nh l mt c trng ca thi gian tan r.
bn ko ca vin nn khong 1,5 MPa cho nh gi ny. Mt ng
biu th theo hm m c s dng cho vic nh gi d liu.

Kt qu l t ban u v s lm t mao dn tng quan vi thi

gian phn hu (Kh ban u R2 = 0,724, s lm t mao dn R2 = 0,939).
C th thy rng kh nng cha nc ca cht ht m c tc ng tch cc
ln thi gian phn hu. MAMS (0,0321 g2 / s), Avicel PH200LM (0,0338
g2 / s), Kollidon CL (0,201 g2 / s) v Avicel PH102 (0,0183 g2 / s) lm t
mao dn nhanh hn ECG 505 v S1500 (khong 0,0001 g / s) . ECG 505 l
cht phn r lm trng n (Fukami v cng s, 2006), v S1500 c c
tnh ging nh ECG505. Kt qu ny cho thy ECG 505 v S1500 c th
ht nc thay i cu trc trong qu trnh hp th m. rt
ngn thi gian tan r, s cn phi s dng mt cht hp th m cao s
dng cho MADG.

3.6. nh hng ca kh nng tm t vin nn trong thi gian tan r

xc nh thi gian tan r ca vin nn sn xut bng MADG c s

khc bit ng k, nh hng ca kh nng cha nc ca cht ht m khc
nhau trong thi gian tan r c kho st.Hnh 7 cho thy m t
ban u v s lm t mao dn nh l mt c trng ca thi gian tan r v
hnh 8 cho thy xp ca vin nn nh l mt c trng ca thi gian tan
r. bn ko ca vin nn khong 1,5 MPa cho nh gi ny. Mt ng
biu th theo hm m c s dng cho vic nh gi d liu.

Cht ph gia Magnesium stearat Mg(C18H35O2)2 thng c s dng

lm cht bi trn. Sau khi nn cht, magi stearate ph ln b mt ca
vin nn. Ngi ta cng bit rng magi stearat c nh hng tiu cc n
s phn r ca vin nn (Uzunovic v Vranic, 2007, Wang v cng s,
2010).Lm t ban u ch c mi tng quan yu vi thi gian tan r (R2
= 0.11) v do ch c th ng gp nh vo thi im tan r khc nhau,
cho thy rng khng hoc ch c s khc bit nh trong phn b magi
stearat trn b mt cc vin nn. Khi xp ca vin nn m vin nn c
cha MAMS cho thy xp cao hn ng k lin quan n vng b mt
bn trong cao hn, xp ca vin nn cha MAMS c th c nh
hng tch cc n thi im phn hu.
 Tuy nhin, khng c s khc bit ng k trong xp gia cc vin
nn MADG khc. t ca mao dn tng quan vi thi gian phn hu
(R2 = 0,686). Ngi ta cho rng magi stearat khng gy nh hng ng
k n cu trc mao dn v do chng ti cho rng thi gian phn hu
nhanh c th l do s t ca mao dn.

4. Kt lun

Chng ti chun b cc vin nn MADG s dng Avicel

PH200LM, Avicel PH102, MAMS, S1500, Koolidon CL v ECG 505. Cc
vin nn ny, ngoi tr S1500, cho thy kh nng nn v phn hy nhanh
chng so vi vin nn sn xut bi HSG. Loi Avicel PH200LM m thp
khng chng minh c bt k u im no so vi Avicel PH102, nh cc
tc gi khc m t trc y. S tan r ca vin nn do MADG sn xut
nhanh hn ng k so vi quy trnh thay th HSG. L do c th l do thm
nc tt hn ca cellulose vi tinh th trong cng thc so vi HSG. Tc
m t ban u v lm t mao dn tng ln. V vy, khng ch t dc ht
m lm tng kh nng hp th m, m cn gp phn lm cho thi gian
tan r nhanh.

Thi gian tan r ca vin nn do MADG sn xut tng quan vi s

lm t ca mao dn. xp ca vin thuc c sn xut bi MADG cho
thy ch c mt nh hng nh n thi gian tan r. C th cho rng thi
gian phn hu nhanh ch yu l lm t mao dn.

Da trn nhng kt qu ny, MADG cung cp mt quy trnh n gin

v tit kim chi ph ngoi vic sn xut vin nn phn hy nhanh.
Li cm n
Chng ti cm n ng Mr.Kenta Fujinuma t i hc Toho v s h tr ca
ng trong phn tch kh nng tm t.

Ti liu tham kho

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