TRP CHi V - DI/pC HOC QUflN S^ s 6 5-2014
NGHIEN COU X A Y DI/NG CONG THOTC MANG BAO CACH LY
CHO PALLET LANSOPRAZOL
Luvng Quang Anh'; Nguyin Nggc Chien"; Nguyin Bang Hoa"
TOM T A T
Nghien ci^u xdy dpng cdng thuc mdng bao each ly cho pellet lansoprazol (LPZ). OS khdo sat dupc dnh hudng cua polyethylen glycol 6000, lutrol, talc va ty le chat rIn trong djch bao din hl$u suit va kha nang giai phdng dupc chit trong mol trudng dpm phosphat pH 6,8 Bao mang each ly su dung polyme Id polyvinyl alcol vdi ty 16 tdng khli lupng so vdi pellet lansoprazol la 7,5%.
' TC^ khod: Pellet; Lansoprazol, Mdng bao each ly.
STUDY ON FORMULATION OF BARRIER COATING OF LANSOPRAZOLE PELLETS
SUMMARYFormulation of banier coating of lansoprazole pellets was studied. The influences of polyethylene glycol 6000, Lutrol, talc and solid percentage on the productivity of pellets, dissolution of lansoprazole from pellets in phosphate buffer of pH 6.8 were evaluated. The lansoprazole pellets were coated with polyvinyl alcohol up to 7.5% weight gain.
' Key words: Pellet; Lansoprazole; Barrier coating.
D A T VA'N B E 'sn d rupt. Han nua, mdng baa cdch ly Lansoprazol id thylc dilu trj loet da =?2^ ' ' f i"^'^ ^ * ' P^"^' "*'^" "'"''^ ""'''' diy - td trang thudc nhdm uc c h i bam =^,^'- Y' "^^^ "3*"^" ""'" ""^^ '^''"^ "^"^
proton, cd sinh kha dyng cao [3, 61. Hi^n *"•= ^ ' i ^ ™ " ? ^^° .<=^'='^ H '=° ^ "9*]'^ " " ^ ^ nay, cdc c h i phim chua LPZ trdn thj trudng *">"3. ^nh huang den dp on anh cua pellet chCi y|y dudi dang vien nang cung chua "^'^'^ '^^S "'"'' P^"^' ^^° ' ^ " " ™«t.
pellet bao tan d rupt vd deu phdi nhdp
ngeai. DP ddc dilm de bj phdn huy trong NGUYEN LIEU, TRANG THIET B| v A mdi trudng axit cua dupc chit, nen mdng PHUONG P H A P NGHIEN CifU bao tan d rupt Id yeu c l y bat bypc chp ^ .. . i . . dang bdp che pellet LPZ [1]. Tuy nhien, ^- ^^"^^" " ? " "' ^'^"^ ' t " ^ ' "!•
do cdc polyme bap tan d rupt thudng cc Nguyen lieu: LPZ dat tieu c h y i n tinh axit, vl chCra nhdm carboxyl t u do [5], Dupc dien My (USP 33), hydroxypropyl anh hudng d i n dd I n djnh cua LPZ, nen methylcellulose El 5 (HPMC), polyvinyl alcol mdng bao cdch ly dupc su dyng de ngan (PVA), dinatri hydrophosphat (Na2HP04), dupc chat t i i p xuc true t i i p vdi mdng bao polyethylen glycol 6000 (PEG 6000), lutrol.
' Hgc vi$n QuSn y
" Bai hoc Duac Hi N0i
NgtfO^ phin hoi (Corresponding): Luvng Quang Anh ([email protected]) Ngiy nhin bii: 01/04/2014; Ngiy phin bifn dinh gia bii bao: 13/05/2014
TRP CHi V - DVgiC HQC O U A N SV s S 5-2014
talc, suglets kich thudc 710 - 850 ym (Colorcon, Singapore) dat tieu chuin dupc dyng. Cdc dung mdi, hod chat khdc dat tieu chuin phan tich.
Trang thilt bj: he thong bao t i n g sdi Diosna (Due), mdy bao tarig sdi mini Caleva (Anh), mdy quang p h i UV - Vis Hitachi U- 1900 (Nhat), mdy sac kj idng hieu ndng cao Shimadzu t(/IQ220 (Nhdt), hp thong thu nghipm hpd tan Erweka DT600 (Duo).
2. Phu'o'ng phdp nghien ciru.
- Bao c h i pellet LPZ bang phuang phdp boi dan vdi suglets la pellet trp, su dung thilt bj ting soi Diosna vdi cdc thong s l ky thuat; nhiet dp khi vdp 50°C, dp md cua cOa gid (Fan) 90%, toe dp phun djch 4,8 - 6,6 ml/phut, dp suit khi phun 1,5 - 2,0 bar, dp suit ru 1,0 bar. Sau dc, bap mdng cdch ly cho pellet bdi d i n bang mdy bao ting sol mini Caleva vdi cdc thdng s l ky thuat: nhipt dd bao 42°C, t i c dp phun djch 40 ml/gid, dp suit khi phun 1,0 bar, khi thii vdc buong bao 80%
vd toe dp rung 10%.
- Hipu suit bao pellet dupc tinh theo cdng thuc:
Trong dd, H: hieu suit bao pellet (%);
m: khoi lupng pellet tang len sau khi bap (g); IVl: khii lupng chit ran trpng djch bao da dCing (g).
- Dp ddy mang bao dupc tinh thep ccng thuc:
D = ( a / b - 1 ) x 100%
Trong dd, D: dp day mdng bao (%); a:
ham iuang dupc chat trudc khi bao (%);
b: hdm lupng dupc chit sau khi bao (%).
Ojnh lupng LPZ trpng pellet bing phuang phdp quang p h i hap thu t u ngoai d budc sdng 283 nm. Dung mdi Id methanol, c6 so sdnh vdi dung djch chuin nIng d^
khodng 10 pg/ml.
- Ddnh gid dd hda tan dupc chat tii pellet: su dgng thilt bj canh khuiy, t i c d§
quay 75 vdng/phut. Mdi trudng thii': 900 ml dung djch dem phosphat pH 6,8, nhiet dp 37 ± 0,5°C. Thdi gian thO: 60 phijt.
IVloi cIc chira lupng pellet tuang ung khodng 30 mg LPZ. Do mat dp quang d budc sdng 283 nm cd so sdnh vdi mdu chuan (n = 3).
- Ddnh gia tinh khdng axit cua pellet:
su dyng thilt bj cdnh khuay, toe dd quay 75 vpng/phut. Mdi tnj'dng thu; 500 ml dung djch axit HCi 0,1 N, nhipt dp 37 ± 0,5°C.
Thdi gian thu: 60 phijt. Mdi c I c chua lupng pellet tuang lung khpang 30 mg LPZ. Tinh thdi gian bat d i u xuit hien pellet bj bien mdu vd ty Ip pellet bj biln mdu sau 60 phCit trong mdi trudng axit HCl 0,1 N (n = 6).
K§'T QUA NGHIEN cCru vA
B A N LUAN1. Anh huwng cua PEG 6000 din hieu suit va kha nang giai phdng LPZ.
Vdi vai trd Id chat hda dep su dyng trpng cdng thuc bap, khdi lupng PEG 6OO0 cd lien quan d i n hipu s u i t bao vd dp dec dai cua mdng bao, vl t h i anh hudng din kha nang giai phdng dupc chat. Tiin hdnh bao cdch ly pellet boi d i n vdi cdng thuc c6 lupng PVA, lutrol, talc co djnh, chi thay doi ty 1$ PEG 6000 trong cdng thuc djch bap.
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TAP CHi y - DirOC HOC OUiiN Sl^ sd' 5-2014 Sang 1; Anh hudng cua ty Ip PEG 6000 den hieu suit bao vd khd ndng gidi phong LPZ.
C6NG THDC PEG 6000 {%) Khi ndng giai ph6ng LPZ (%)
H i $ u s u ^ t t ) a n ( % ) Qud trinh bao
CONG T H Q C 1 1,0 69,29 69,24 Nhi^u bvi
CONG THilrc 2 1,25 90,85 76,65 Nhi^u bMi
C O N G T H Q C 3
1.5 90,46 85,89 Thu?n Ipi
Khi tdng ty Ip PEG 6000, hipu suit bao tang len, nhung khd ndng gidi phdng dupc chit khdng thay dii. Hipu suit bao dat cao nhit khi ty ip PEG 6000 Id 1,5%. Vi vay, lua chpn ty Ip nay d l khap sdt tiep thee.
2. Anh hu'dng cua lutrol d i n h i f u s u i t bao vd kha nang giai phdng LPZ.
Lutrol dupc su dyng trcng cdng thdc djch bao, vi nd Id td dupc on djnh trong nhilu dgng bdo chi. Dong thdi, lutrol it hut am trong qud trinh bao qudn, nen Idm tang do on djnh cua mdng bao cung nhu cua pellet nhdn [2, 5]. Tuy nhien, vdi tinh chdt Id mdt polyme, nen ty Ip lutrol khdc nhau cung anh hudng den hipu suit bao vd khd ndng gidi phdng dupc chit tO pellet.
Bang 2: Anh hudng cua lutrpl d i n hl#u suit bao vd kha ndng giai phpng LPZ.
CONG T H Q C Lutrol (%)
KhS nang g i l i pli6ng LPZ (%) Hi$u suSt bao (%) Qud trinh bao
CONG T H Q C 4 0,5 84,62 76,27 NhiSu bui
C 6 N G T H Q C 3
1,0 90,46 85,89 Thuan l<?i
CONG T H Q C 5 1,5 89,68 81,62 T h u | n l<?i
CONG THCfC 6 2,0 90,03 75,56 Kh6 khan
Khi tang ty 10 lutrol, kha nang giai phong du'Q'c chat tang len, dong thoi cung l^m tang hi0u suat bao. Nhu'ng khi ty le lutrol tang cao (2%), dich bao c6 dp nh61 cao, gay kho khan cho qua trinh bao v^ Icim giam hi$u su^t bao. Vi vgy, ty le lutrol 1% du'Q'c iLra chpn cho cac kh^o sat tiep theo.
3. Anh hiFO'ng cua khdi iLrgng talc d§n hieu sudt bao.
Sang 3:
C6NG THQC Taic (%)
Kha nSng giai ph6ng LPZ (%) Hi$u su^t bao (%)
Qud trinh bao
C O N G THCfC 7 0,5 91,05 79,22 Hi$n lu'O'ng c6
pellet bl dinh
C 6 N G THCfC 8 1.0 90,32 8 1 , 4 9 Hi^n tiPffng c6
pellet bi dinh
CONG T H Q C 3 1.5 90,46 85,89
ThuSn li?'i
C 6 N G T H O C 9
2,0 90,55 7 5 , 6 7
N h i k bui
Khi s u dyng talc vdi ty 1$ 0,5% vd 1,0% (ccng thirc 7 vd ccng thuc 8) cp hipn
tupng pellet bi dinh del hoac dinh ba, hipu suit bap chi dat khpang 80%. Qud trinh
TnP CHi V - DV9IC HOC OUAN SV sS 5-2014
Tuy nhien, khi tang ty le talc len 2,0% (cdng thuc 9), hipu suit bao gidm rd r$t, xull hien nhieu byi chit ran trong budng bao.
4. Anh hudng cua ty le chit rdn trong djch bao din hieu suit bao.
Bang 4:
CONG THQC Dung m6i (ml)
Ty 1$ chit f i n trong djch bao (%) KhS nSng giai phdng LPZ (%) Hi^u suit bao (%) Qud trinh bao
CONGTHOCIO 26 7,6 89,36 81,35 Thuan i(?i
CdNG THQC 3 20 10 90,46 85,89 Thu§n M
CONG THQC 11 16 12,5 91,12 75,30 Kh6 khan
CONG THQC12 13 15
Kh6 khan
((-): khong do dwQc)
Ty ip c h i t ran trong djch bao anh hupng d i n the chit djch bao vd hieu suit bao. Khi tdng lupng chit ran trcng djch bao, djch bao cd do nhdt cao, qud trinh bao gap khd khan, hieu suit bao giam.
Vdi ty le chit rdn trong djch bao chiim 15%, Sling phun bj tac, qud trinh bao khdng t h i tiip tyc. Vdi lupng chit ran trong djch bao thip, qud trinh bao thudn lpi, nhung se bi keo ddi. K i t qud cho thiy: khi ty Ip chit ran thay doi tiJ' 7,5 -12,5%, khd nang giai phdng dupc chit khdng thay d i i . Hipu suit bao dat cao nhat khi ty Ip chit ran Id 10% vd qud trinh bao thudn Ipi.
Vi vay, lua chpn ty le chat ran Id 10% che cac khao sdt tiip theo.
5. Anh hu-dng cua do day mang bao din hipu suit, kha nang giai phong LPZ tCr pellet bao each ly vd tinh khdng axit cOa mang bao tan d rudt.
Pellet bdi d i n duac bao each ly vdi SI) ddy mdng bao khdc nhau, sau dd bao tan d rupt tdng 25% khoi lupng so vdi pellet dd bao cdch ly, mdng bao tan d rupt co cdng thCrc bac g i m eudragit L100, triethyl citrat, titan dipxyd, talc, su dyng dung moi Id hdn hpp ethanol/nudc. Cdc mdu pellet bao tan d rupt dupc thu dp hda tan trong mdi trudng axit HCl 0,1 N trong 60 phiit de ddnh gid sa bp v l khd nang khang axit cua mdng bao.
Sang 5; Anh hudng cua dp ddy mdng bap den hipu suit, khd nang giai phdng LPZ tu pellet bap each ly vd tinh khdng axit cua mdng bao tan d rupt.
CdNG THQC Dp ddy mdng bao each ly (%) Kha nang giai phong LPZ (%) Hi$u su^t bao cdch ly (%)
Thoi gian bdt 6ku xuit hign pellet bao tan b ruOt bj bi4n mdu (phijt)
Ty le pellet bao tan o- nigt bj bien mdu sau 60 phut (%)
CONG THOC 3 5 90,46 85,89 32 23,65
CONG THQC 13 7,5 91,58 84,49 56 2,12
CONG THOC 14 10 89,80 83,93 56 2,05
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TAP CHf V - DirOC Hpc QURN S^^ Sd' 5-2014
Khi dp ddy mdng bao tdng len, kha
ndng gidi phdng dupc chit trong mdi trudng dem pH 6,8 nhu nhau, hidu suit bao thay doi khdng ddng k l . 0 cdng thuc 3, chi sau khodng 32 phut dd xuit hipn pellet bj biln mdu. C) cdng thuc 13 vd cdng thuc 14, thdi gian ndy g i n 60 phut.
Ty le pellet bao tan d rupt bj bien mdu sau 60 phut rat thip d cdng thuc 13 vd cdng thuc 14 (khodng 2%). Kit qua oho thiy; dp ddy cua mdng bac each ly cOng Idm tang kha ndng khdng axit cua pellet bao tan d rudt. Id Idp bao ve thu hai cho pellet nhdn khi mpt phan moi trudng axit da thim qua Idp mdng bao tan d rupt sau thdi gian thCf nghipm. Dd ddy mdng bao 7,5% (cdng thuc 13) dupc lua chpn d l tien hdnh bae cdch ly che pellet nhdn chua LPZ.
KET L U A N
Dd xdy dung dupc ccng thuc cua mdng bac cdch ly cho pellet nhdn chua LPZ (pellet nhdn dupc bdp c h i bang phuang phdp bdi dan). Thdnh phin cua mdng bac cdch ly gdm polyvinyl alcol, polyethylen
glycol 6000, lutrol, talc dupc hda tan va phdn tdn deu trong dung mdi thich hpp.
Bao mdng cdch ly bang polyvinyl alcol vdi ty le 7,5% so vdi pellet nhdn chua LPZ
T A I Lieu THAM K H A O
1. Bt mon Bio chS. Mdt s6 chuySn d l v l bdo che hipn dpi. Tdi ll$u ddo tgo sau dai hpc.
Trudng Oai hpc Dupc Hd NOi. 2005.
2 Hoing Ngoc Hung, VQ Chu HUng Ta dupc vi chat phy gia dCing trong dupc pham, m? p h i m vd thuc pham NXB Y hoc. 2006.
3 Horn JR et al. Similarities and differences among delayed release proton-pump inhibitor formulations Aliment Pharmacol Ther. 2005, 22, pp.20-24.
4. Rahman MA et al. Recent advances in pelietization technique for oral drug delivery:
A review. Current Drug Dev. 2009, 6 (1), pp. 122-129.
5. Rowe RC et al. Handbook of phannaceutlcal excipients. Pharmaceutical Press 2009.
6. Shi S etal Proton pump inhibitor an update their clinical use and pharmacokinetics. Eur J Clin Pharmacol. 2008, 64, pp.936-951.
