Nghiên cứu ảnh hưởng của hydroxypropyl-β-cyclodextrin đến độ ổn định của thuốc tiêm đông khô phantoprazol

N g h i e n CLFU - Ky t h u a t<br /> <br /> <br /> Nghien ciru anh htfong ciia hydroxypropyl-p-<br /> r f r<br /> <br /> cyclodextrin den do on dinh cua thuoc tiem<br /> dong kho pantoprazol<br /> Pham Xuan Chung, Nguyen Van Long,<br /> Dao Minh Huy, Nguyen Minh Trang<br /> Truang dai hoc Dugc Ha Noi<br /> <br /> Dat van de - Tu siy, tu vi khi hau CLIMACELL.<br /> Pantoprazol (PTZ) la mdt chit thude nhdm - May phan tieh nhiet vi sai SETARAM<br /> benzimidazol. Cung gidng nhu cae chit khac ciing DSC131.<br /> nhdm, PTZ khdng bin, d i bi phan huy trong mdi Phu'ang phap nghien eu'U<br /> trudng acid '^' ®' nen da cd nhiiu bien phap duge ap Phuang phap phan tich nhiet vi sai (DSC)<br /> dung d i lam tang do dn dinh cua ehung nhu: sii' Nghien ciru tinh c h i t nhiet hgc va tuang tac<br /> dung ta dugc kiim '^°' hoac hdn hgp ta duge kiim hda ly cua PTZ vdi ta duge, tir dd lya chgn<br /> '"*', sir dung cac chit chdng oxy hda, bao c h i dang duge cae ta duge lam tang tinh dn dinh cua<br /> vien bao tan trong rudt '^®' hoac dang thude tiem hoat chit trong edng thu'C thude tiem ddng khd<br /> ddng khd... Muc tieu eua nghien eiru nay la danh PTZ bing phuang phap phan tich nhiet vi sai<br /> gia anh hudng cua hydroxypropyl-p-cyclodextrin (DSC). Vdi eae d i i u kien:<br /> din do dn dinh eua thude tiem ddng khd PTZ. - T d e d g q u e t 10°C/phut<br /> Nguyen lieu, thiet bj va phu'O'ng -Khoang quet-25-250°C.<br /> - M i u chuan: nhdm hydroxyd.<br /> phap<br /> - Mdi trudng: khdng khi.<br /> Nguyen lieu<br /> Phuang phap dong kho<br /> - Natri pantoprazol sesquihydrat x u i t xir:<br /> Bao c h i thude tiem ddng khd PTZ 40 mg<br /> . Tay Ban Nha, dat tieu ehuin Dugc dien Chau<br /> Au (EP6). bing phuang phap ddng khd vdi cac thdng sd:<br /> -Ddng lanh: -70°C, thdi gian: 6 gid.<br /> - Cac ta duge: natri hydroxyd, manitol,<br /> arginin, dinatri EDTA (Trung Qudc), - s i y sa c i p : -15°C, thdi gian: 20 gid, tdc do<br /> hydroxypropyl-p-cyclodextrin (Trung Qudc) dat gia nhiet 0,5°C/1 phut.<br /> tieu ehuin nha san x u i t - s i y thir c i p : +25°C, thdi gian: 20 gid, tde<br /> - Cae hda chit tinh khiit phan tich: acetonltril, do gia nhiet: 0,25°C/1 phut<br /> natri dihydrophosphat dinatri hydrophosphat Phu'O'ng phap sac ky long hieu nang cao<br /> dikali hydrophosphat va acid phosphoric (Merck), (HPLC)<br /> dat tieu chuan nha san x u i t Xae dinh ham lugng PTZ va ty le tap c h i t<br /> - Niit nhdm (Viet Nam), nut cao su f^isc), Ig trong c h i p h i m thude tiem ddng khd bing<br /> thuy tinh trung tinh i^uic), dat tieu ehuin nha phuang phap HPLC. Vdi cac d i i u kien:<br /> san xuit. - Pha ddng: Acetonltril va dem phosphat pH7.<br /> T h i i t bj - Cot HPLC: C I 8 (5 |j.m) 4,6 X 150mm.<br /> - May ddng khd LABCONCO. - Detector tu" ngoai: bude sdng 290nm.<br /> - May Ige mang SATORIUS vdi mang Ige ed - T h i t i e h tiem: 20pl.<br /> kich thude 0,2ijm. - Tdc do ddng: 1 ml/phut<br /> - May do pH Inonab pH 370. Phu'O'ng phap lao hoa cap toe<br /> - May s i c ky Idng hieu nang cao hieu Danh gia mgt sd chi tieu chit lugng eua thude<br /> SHIMADZU 10AVP. tiem ddng khd nhu: hinh thu'C cua bgt ddng khd;<br /> <br /> TAP CHI DUOC HOC - 12/2010 (SO 416 NAM 50) 19<br />  Nghien CLFU - Ky thuat<br /> mau sic, do trong eiia dung djch pha lai; ham nhiet manh khoang 160-170°C (tuang irng diem<br /> lugng PTZ, ty le tap chit. Vdi cac diiu kien: chay eua manitol), mdt pic tda nhiet khdng dac<br /> • - Cudng birc: trong tu 100°C. tarng khoang 190°C (tuang U'ng nhiet do phan<br /> - Trong tu vi khi hau: nhiet do 40°C ± 2, do huy eua PTZ) cd cudng do tuang irng (8mW va<br /> i m 75 ± 5%. 21,4mW) thip han so vdi pic tda nhiet ciia PTZ<br /> trong hon hgp M l (53mW) va PTZ ty do<br /> - D i i u kien phdng thi nghiem: nhiet do 25 -<br /> (130mW). Diiu nay cd the dugc giai thieh nhu<br /> 35°C, do i m 55% - 85%.<br /> sau: HP-p-Cyd la ta dugc cd kha nang dn djnh<br /> K§t qua nghien CIFU va ban luan cac hoat chit khdng b i n , do tao ra cae khung bao<br /> Kit qua nghien CLPU anh hu'O'ng cua bgc xung quanh phan tu hoat chit cho nen han<br /> hydroxypropyl-p-cyclodextrin d i n do 6n ehi sy tiip xue eua hoat chit vdi mdi trudng xung<br /> djnh cua PTZ quanh, tuy nhien day ehi la hdn hgp vat ly nen vin<br /> Danh gia anh hudng cua hydroxypropyl-p- edn cac phan tir PTZ ty do, trong qua trinh gia<br /> cyclodextrin (HP-p-Cyd) d i n do dn dinh cua nhiet ehi nhO'ng phan tCr PTZ tiip xiic vdi HP-p-<br /> PTZ trong cac hdn hgp vat ly M l , M2, M3 gdm: Cyd mdi tao phu'c hdn hgp PTZ - HP-p-Cyd, hdn<br /> PTZ, manitol va HP-p-Cyd bing phuang phap hgp nay b i n vu'ng vdi nhiet han so vdi PTZ ty do<br /> DSC vdi eae diiu kien dugc ghi d phin trong khoang nhiet do da khao sat, do dd cudng<br /> Phu'O'ng phap phan tich nhiet vl sal. K i t qua do pic chi giam di nhieu chir khdng m i t (Jdng thdi<br /> dugc trinh bay trong bang 1 va hinh 1: cudng do eua pic cung phu thugc vao ty le HP-p-<br /> Cyd ed trong hdn hgp.<br /> Bang 1: Thanh phin hdn hap vat ly<br /> Thanh phan Ml M2 M3 Nhu vay, trong hdn hgp vat ly vdi manitol va<br /> Manitol (mg) 120 120 120 HP-p-Cyd, PTZ b i n vu'ng vdi nhiet han, ty le HP-<br /> p-Cyd ed trong hdn hgp cang Idn, PTZ cang bin<br /> PTZ (mg) 50 50 50<br /> virng. K i t qua nay cung phii hgp vdi nghien eiru<br /> HP-(3-Cyd (mg) 50 150<br /> eua M.EI-Badry va cdng sy v i anh hudng eua ty<br /> Ty le PTZ:HP-p-Cyd 1:0 1:1 1:3<br /> le HP-p-Cyd trong hdn hgp (omeprazol:HP-p-Cyd)<br /> d i n do dn dinh cua omeprazol (mdt chit trong<br /> nhdm benzimidazol)'^l<br /> Kit qua danh gia anh hu'ong cua HP-P-Cyd<br /> din do 6n djnh ciia thude tiem dong kho PTZ<br /> Tren ca sd k i t qua thu dugc tir phuang phap<br /> DSC vdi hdn hgp vat ly, tiin hanh bao c h i thude<br /> tiem ddng khd PTZ vdi m i u CT233 ed HP-p-Cyd<br /> va m i u CT234 khdng cd HP-P-Cyd. Mdi me ddng<br /> khd 200 Ig theo ciing mdt quy trinh.<br /> Danh gia bang cam quan va bang phuvng<br /> phap HPLC<br /> San phim sau khi ddng khd duge theo ddi<br /> Hinh 1: Dwang biiu diin phan tich nhiet vi trong diiu kien cudng birc, eu the: Cae m i u<br /> sai (DSC) cua PTZ (1), manitol (2), HP-^-Cyd duge 6§ trong tu 100°C. Mdi 2 gid, kiem tra hinh<br /> (3), hdn hap Ml (4), M2 (5) va M3 (6). thirc, mau s i c cua banh thude; mau s i c , do due<br /> Kit qua hinh 1 eho thiy: Dudng nhiet cua eae eua dung dich pha lai vdi 2,5ml nude c i t pha<br /> hdn hgp vat ly M2, M3 gdm PTZ, manitol, HP-P- tiem; ham lugng hoat c h i t va ty le tap chit<br /> Cyd ed pic rdng trong khoang 50-100°C (tuang dugc xac djnh b i n g phuang phap HPLC. Kit<br /> U'ng vdi sy mit nude cua HP-p-Cyd), mdt pic thu qua dugc trinh bay trong bang 2 va 3:<br /> Bang 2: Anh hwang cua HP-^-Cyd din hinh thuc bdt va dung dich pha lai cua thude tiem ddng khd PTZ<br /> Bgt dong kho Dung dich pha lai<br /> Thai gian<br /> CT233 CT234 CT233 CT234<br /> 0 gid Hinh banh thuoc,trang, min Hinh banh thu6c,trang, min Trong, kh6ng mau Trong, kh6ng mau<br /> Sau 2 gid Hinh banh thuic, tring, min Hinh banh thuic, tring, min Trong, kh6ng mau Trong, khong mau<br /> Sau 4 gid Hinh banh thuic, tring, min Hinh banh thu6c, Trong, kh6ng mau Trong, mau vang<br /> vang, kh6ng min nhat<br /> <br /> <br /> 20 TAP CHI Dl/OC HOC - 12/2010 (SO 416 NAM 50)<br /> • Nghien CLFU -• Ky thuat<br /> Bang 3: Anh hwang cua HP-P-Cyd din dodn dinh cua thude tiemddng khd PTZ<br /> Ham Iwg'ng (%) PTZ Ty le (%) tap chat<br /> Thcyi gian<br /> CT233 CT234 CT233 CT234<br /> 0 gid 103,01 104,92% 0,06% 0,09%<br /> Sau 2 gid 99,51 99,05% 0,71% 1,32%<br /> So sanh Giam 3,50% Giam 5,87% Tang 10,8 l l n Tang 14,6 lan<br /> Sau 4 gid 97,96% 95,73% 1,56% 4,51%<br /> So sanh Giam 5,05% Giam 8,19% Tang 26 lan Tang 50,1 lan<br /> <br /> K i t qua bang 3 cho thiy: sau 2 gid d i d d i i u 234 d i u eho pie thu nhiet tai khoang tir 160-<br /> kien cudng birc (nhiet do 100°C), ham lugng 170°C tuang irng vdi nhiet do ndng chay<br /> PTZ trong san phim pha c h i theo edng thire manitol (cudng do tuang u'ng la-90mW va -<br /> 233 giam it han so vdi san phim ddng khd theo 138mW) va ngay sau khi ndng ehay la mgt trang<br /> cdng thu'C 234 (3,05% va 5,87%), trong khi ty le thai tda nhiet khdng dac trung (tuang quan vdi<br /> tap chit bj phan huy eung ft han (0,71% - tang nhiet do phan huy cua PTZ - 190°C) vdi cudng<br /> 10,8 lin va 1,32% - tang 14,6 lin). Sau 4 gid, do tuang irng 34mW va 80mW, chu'ng td sau khi<br /> tuang u-ng la (5,05% va 8,19%) va (1,56% - ddng khd PTZ khdng edn d dang tinh t h i ma da<br /> tang 26 lin va 4,15% - tang 50,1 lin). chuyin sang dang vd djnh hinh. Tuy nhien, cudng<br /> Danh gia bang phwcrng phap DSC do cua eae pie tren dudng nhiet eua san phim<br /> Cae san phim ddng khd theo edng thu'C 233 ddng khd theo edng thirc 233 d i u thip han cudng<br /> va 234 dugc danh gia bing phuang phap DSC do cac pic tuang u'ng tren dudng nhiet cua san<br /> vdi cac diiu kien dugc ghi d phin Phu'ang phim ddng khd theo cdng thire 234.<br /> phap phan tich nhiet vi sal. K i t qua duge trinh Nhu vay, k i t qua tu* phuang phap DSC phu<br /> bay trong hinh 2: hgp vdi kit qua thu duge tu" phuang phap HPLC,<br /> ca hai phuang phap d i u eho thiy bdt ddng khd<br /> theo edng thire 233 b i n virng vdi nhiet han bdt<br /> ddng khd theo edng thu-c 234, diiu nay chu'ng td<br /> ring HP-P-Cyd da lam tang do dn djnh vdi nhiet<br /> ciia thude tiem ddng khd PTZ.<br /> K i t qua nay eung phii hgp vdi nghien eu'U<br /> ciia mgt sd tac gia tren t h i gidi v i anh hudng<br /> cua HP-P-Cyd vdi mdt sd c h i t trong nhdm<br /> benzimidazol [^-^•^".<br /> Tu' k i t qua thu dugc, cac me t i i p theo sir<br /> dung HP-p-Cyd lam ta dugc de dn djnh thude<br /> tiem ddng khd PTZ.<br /> Kit qua nghien eu'U anh hu'O'ng eua ty le<br /> HP-P-Cyd d i n do 6n dinh eua thude tiem<br /> Hinh 2: Dwang biiu diin phan tich nhiet vi sai ddng kho PTZ<br /> (DSC) cua PTZ (1), manitol (2), HP-^-Cyd (3), bdt T i i n hanh ddng khd vdi eiing mgt quy trinh<br /> ddng khd cua cdng thirc 234 (4) va 233 (5) ky thuat cac edng thire ed eung ta dugc k i i m , ta<br /> Kit qua hinh 2 eho thiy: Dudng nhiet eua dugc tao khung, ta dugc chdng oxy hda, nhung<br /> san pham ddng khd theo cac cdng thirc 233, sir dung lugng HP-p-Cyd khac nhau:<br /> Bang 4: Khdi Iwang HP-p-Cyd sw dung trong cac cdng thirc thude tiem ddng khd PTZ<br /> Cong thii-c 306Y 3063 871 872 873 3182 2872 1971 7972 ^973 1974 1975<br /> Kh6i lugng<br /> HP-p-Cyd 50 100 150 200 300 350 400 450 600 750 900 1050<br /> sir dung (mg)<br /> <br /> <br /> <br /> TAP CHI DUOC HOC - 12/2010 (SO 416 NAM 50) 21<br />  Nghien CLFU - Ky thuat<br /> Danh gia bing cam quan va bing phipcmg nay khdng t i n hanh danh gia cae chT tieu khac.<br /> phap HPLC - San phim sau khi ddng khd theo cae edng<br /> vi cam quan thu^ 3061; 3063; 871; 872; 873: 3182: 2872 cd<br /> - Cac m i u pha e h i Iheo cdng thire 1972; 1973; hinh banh thude dep, mjn, cho nen tiip tuc danh gia<br /> 1974; 1975 khdng ddng lanh, khdng thanh hinh cae chi fieu khae nhu ham lugng hoat c h i t ty le tap<br /> banh thude hoac banh thude cd t>i mat khdng mjn, chat Tiin hanh lao hda cudng birc vdi cae diiu<br /> cd tach Idp. khdng xdp (cdng thire 1971). VI vay, kien nhu d phin Phipong phap lao hoa cip tdc.<br /> eae san phim sau ddng khd theo cac cdng thirc K i t qua dugc trinh bay trong bang 5 va hinh 3:<br /> Bang 5: Ham Iwang (%) PTZ va tyle (%,) tap chitcua thude tiem ddng khd PTZ trong cac cdng thirc<br /> Thai gian CT3061 CT3063 CT871 CT872 CT873 CT3182 CT2872<br /> 0 gid 100,01 99,89 106,70 102,30 106,70 100,08 107,6<br /> <br /> Ham Iwang Sau 2 gid 95,51 96.38 103,49 99,28 104,14 97,95 105,55<br /> (%) So sanh (giam %) 4,50 3,51 3,21 3,02 2,56 2,13 2,15<br /> pantoprazol Sau 4 gid 93,96 94,33 102,20 98,30 103,19 97,06 104,48<br /> So sanh (giam %) 6,05 5,56 4,50 4,00 3,51 3,02 3,12<br /> Ogid 0,12 0,13 0,12 0,12 0,09 0,08 0,09<br /> Sau 2 gid 1,21 1,13 1,01 0,99 0,59 0,43 0,51<br /> Ty le (/a) So sanh (lln) 10,08 8,69 8,42 8,25 6,56 5,38 5,67<br /> tap chat<br /> Sau 4 gid 2.51 2,00 1,71 1,53 1,01 0,89 0,91<br /> So sanh (lln) 20.92 15.38 14.25 12,75 11.22 11.13 10,11<br /> <br /> 3 -<br /> <br /> j<br /> 1 2,5- ,<br /> (%)<br /> <br /> <br /> <br /> <br /> • " I ? - '"»<br /> o<br /> \^<br /> — • — Sau 2 gicT<br /> Q. 1.5 - •^. -^ -Sau2opcr<br /> — » — Sau4gicr Sau4^<br /> ~-*^ "~ —*-<br /> 1<br /> P *^^\ "^^^'^ *<br /> j 0.5-<br /> <br /> 0 -<br /> 0 50 100 150 200 250 300 350 4O0)4S0<br /> 450 () 50 100 150 200 250 300 350 4O0 450<br /> <br /> Ltpcmg h f - p - C y d SLP d u n g i LifOTig rP-p-Cyd si> dung<br /> !<br /> s<br /> (b)<br /> <br /> Hinh 3: Dd thi bieu diin sw phu thude cua ty le tap chat va do giam ham Iwang PTZ<br /> vao Iwgng HP-fi-Cyd trong thanh phin thude tiem ddng khd PTZ<br /> (a)- Bp giam ham lugng PTZ sau 2 va 4 gid; (b).'Fy le tap chit trong bot dong kh5 sau 2 va 4 gid<br /> K i t qua tren eho t h i y vdi ciing thanh phin la (6,05%) va (2,51% - tang 20.92 lin). Trong<br /> trong cdng thirc, do dn dinh eua thude tiem ddng khi dd n i u lugng HP-P-Cyd sir dung la<br /> khd PTZ 40mg phu thude vao lugng HP-p-Cyd 350mg/lg, san p h i m ddng khd sau 2 gid d i d<br /> su= dung. Lugng HP-P-Cyd sir dung cang nhiiu nhiet do 100°C, ham iugng PTZ trong san phim<br /> do dn dinh cua thude tiem ddng khd PTZ cang pha e h i theo cdng thu'C 3182 chT giam (2,13%),<br /> cao. Vdi lugng HP-p-Cyd sir dung la 50mg/lg, ty le tap chit (0,43% - tang 5,38 lin), sau 4 gid,<br /> san phim ddng khd sau 2 gid de d nhiet do tuang irng la (3,02%) va (0,89% - tang 11,13<br /> 100°C, ham lugng PTZ trong san p h i m pha e h i lin). Tuy nhien, n i u t i i p tuc tang lugng HP-P-<br /> theo cdng thire 3061 giam (4,5%i), ty le tap c h i t Cyd SLf dung trong cdng thuc thi khdng nhung<br /> (1,21% - tang 10,08 lin), sau 4 gid, tuang irng do dn ^ n h cua thude tiem ddng khd PTZ khdng<br /> <br /> <br /> 22 TAP CHi DU'OC HOC - 12/2010 (SO 416 NA.M 50)<br />  N g h i e n CLFU - Ky t h u a t<br /> tang (nhu san phim bao e h i theo edng thirc P-Cyd ed trong cdng thire. Trong nghien ciru<br /> 2872) ma cdn khdng ddng khd duge (nhu dung nay, thude tiem ddng khd PTZ 40mg dn djnh<br /> djch pha c h i theo cae cdng thuc 1972; 1973; han ea khi su" dung 350mg/lg HP-p-Cyd.<br /> 1974; 1975) hoic hinh thue x i u (khdng thanh - K i t qua danh gia do dn djnh cua thude tiem<br /> hinh banh thude, khdng xdp) nhu san phim ddng PTZ bing phuang phap HPLC phu hgp<br /> ddng khd theo cdng thire 1971. vdi k i t qua tu- phuang phap DSC.<br /> Danh gia bang phuveng phap DSC<br /> Cae san pham ddng khd duge danh gia bing Summary<br /> phuang phap HPLC ddng thdi eung duge danh Hydroxypropyl-p-cyclodextrin increase the<br /> gia bing phuang phap DSC vdi eae diiu kien stability of pantoprazole in lyophilized injectable<br /> dugc ghi d phin Phu'ang phap phan tich nhiet powder. However, the stability depends on the<br /> vl sai. Kit qua duge trinh bay trong hinh 4: proportion of hydroxypropyl-P-cydodextrin in the<br /> formulation. The research indicates that,<br /> pantoprazole lyophilized injectable powder is the<br /> most stability with hydroxypropyl-p-cyclodextrin<br /> 350mg/vial. The pantoprazole stability were<br /> evaluated by method DSC and HPLC.<br /> A formulation consists of pantoprazole sodium<br /> sesquihydrate, sodium hydroxide, mannitol,<br /> disodium EDTA, hydroxypropyl-p-cyclodextrin with<br /> reasonable proportion and water for injection were<br /> improved. Pantoprazole lyophilized injectable<br /> powder was prepared in laboratory scale, each<br /> batch comprised 200 vials.<br /> Hinh 4: Dwang biiu diin phan tich nhiet vi<br /> sai (DSC) cua PTZ (1), manitol (2), HP-p-Cyd Tai lieu tham khao<br /> (3), bot dong khd theo cdng thirc 3061 (4), 871 1. A.KristI, Acido-basic properties of proton pump<br /> (5), 873(6) va 3182 (7). : inhibitors in aqueus solutions, Drug Dev. Ind. Pharm.,<br /> Kit qua hinh 4 eho thiy: Dudng nhiet ciia (2009), 35, p. 114-117.<br /> san phim ddng khd theo cae edng thire 3061; 2. Ana Figueiras et al. Solid-state characterization<br /> 871; 873; 3182 d i u khdng ed pie phan hiiy cua and dissolution profiles of the inclusion complexes of<br /> PTZ, tuy nhien cudng do eiia eae pic thu nhiet omeprazole with native and chemically modified beta-<br /> cyclodextrin, Eur J. Pharm. Biopharm., (2007), 67,<br /> khae nhau phu thugc vao lugng HP-p-Cyd cd<br /> p.531-539.<br /> trong edng thire, trong dd bdt ddng khd theo<br /> 3. Ana Figueiras et al, In vitro evaluation of natural<br /> edng thuc 3182 (su- dung HP-p-Cyd 350mg/lg)<br /> and methylated cyclodextrins as buccal permeation<br /> ed cudng do pic thip n h i t enhancing system for omeprazole delivery, Eur. J.<br /> Nhu vay, k i t qua tu' phuang phap DSC eung Phanv. Biophanv., (2009), 71, p. 339-^45, .<br /> phii hgp vdi k i t qua thu dugc tu' phuang phap 4. Ana Figueiras et al, The role of 1-arginine in<br /> HPLC, ea hai phuang phap d i u cho t h i y bdt inclusion complexes of omeprazole with cyclodextrins,<br /> ddng khd theo cdng thu'C 3182 su' dung HP-p- AAPS PhamiSciTech., (2010), 11,1, p. 233-240.<br /> Cyd 350mg/lg b i n vu'ng vdi nhiet han ca, d i i u 5. Chantal Holvoet et al. Development of an<br /> nay eung phii hgp vdi k i t qua nghien ciru anh omeprazole parenteral formulation with<br /> hudng eua ty le HP-p-Cyd d i n do dn djnh cua hydroxypropyl-beta-cyclodextrin, Pharm. Dev.<br /> Teehnol., 12, p.327-336, (2007).<br /> PTZ trong hdn hgp vat ly.<br /> 6. M.EI-Badry et al. Effects of Kollicoat IR and<br /> Kit l,uan hydroxypropyl-beta-cyclodextrin on the dissolution<br /> Tu' nhirng k i t qua nghien ciru, thye nghiem rate of omeprazole from its microparticles and enteric-<br /> thu duge, riit ra mdt sd k i t luan: coated capsules, Phanv. Dev. Teehnol., (2010), 15,<br /> - HP-p-Cyd lam tang do dn djnh PTZ. Tuy 5, p.500-510.<br /> nhien, mu'C do dn djnh phu thude vao lugng HP- >•; • (Xem tiep trang 13)<br /> <br /> TAP CHi DUOC HOC - 12/2010 (SO 416 NAM 50) 23<br />  Nghien CLFU - Ky thuat<br /> Ket luan san xuit dugc 5% thiit bj y t i hien dai.<br /> v i mang lu'ai phan phdi TTB y t§ Phin ldn TTB y t i tap trung d cae benh vien<br /> He thdng phan phdi TTB y t i dugc hinh Idn d thanh phd Idn nhu Ha Ngi, TP Hd Chi<br /> thanh tir TW d i n dja phuang va dugc m d rdng Minh, Da Ning... la nhO'ng nai cd he thdng y t i<br /> vdi sy tham gia cua nhiiu thanh phin kinh t i phat triin, dan sd ddng va giao thdng thuan Igi.<br /> nhu: Doanh nghiep nha nude, cdng ty TNHH, Summary<br /> cac cdng ty lien doanh... trong dd eae cdng ty To complete our medical facilities supply<br /> TNHH ludn ehiim ty le cao nhit. Nam 2008 ed system which Is aimed to improve the quality of<br /> 751 cdng ty TNHH tham gia kinh doanh TTB y heathycare service and disease prevention for<br /> t i . Pham vi hoat ddng cua eae DN nay r i t rdng, our people, by retrospective method, we have<br /> duge quyin kinh doanh cac mat hang do Bd Y done a survey on the whole system and come to<br /> t i quy djnh. the findings as follow: the medical facilities<br /> sd lugng cac ca sd san x u i t TTB y t i tang supply system is widespread and has a pool of<br /> nhanh qua cac nam g i n day, nam 2008 ed 56 1.157 teachnical staff (in2007). In 2008, there<br /> ea sd, tang 16,7 % so vdi nam 2007 were 751 companies, most of which are liability<br /> limited ones, involving in this system. In 2008,<br /> Nam 2008 ca nude cd 13.433 ea sd y t i sir<br /> the number of medical facilities importing<br /> dung TTB y t i , trong dd cac benh vien ehiim<br /> companies was 650 in group 4,2%, and 10,85%<br /> 6,73% tren tdng sd nhung gia trj d i u tu TTB y<br /> up as compared with 2007 and 2006<br /> t i lai r i t Idn.<br /> respestively. The import value of medical<br /> v i c l u ngudn nhan lye trong nganh TTB<br /> facilities was 202,5 milion USD, in 2008<br /> y t§<br /> increased by 5,6% against 2007, etc.<br /> Nhin Chung cdn thiiu can bd du nang lye<br /> The Ministry of health and Department of<br /> quan ly chuyen mdn ky thuat va nghiep vu<br /> Medical facilities and Works continue to provide<br /> thuang mai. Sy phan bd ngudn nhan lye khdng<br /> instructions on the implementation of the<br /> diu, ehu y i u tap trung d cae thanh phd Idn.<br /> National medical facilities policy and the Project<br /> V§ cc c l u va s y phan bd TTB y t i tren thj on the reseach and manufacturing of medical<br /> tru'd'ng facilities with a focus on strengthening State<br /> Trang thiit bj y t i nude ta da phin la duge management over medical facilities and human<br /> cac cdng ty nhap khiu tir nhiiu nude tren t h i development for medical facilities.<br /> gidi. Nam 2007 cd 70 thj trudng eung c i p TTB y Tai lieu tham khao<br /> t i cho Viet Nam, tdng gia trj nhap khau dat<br /> 1. Bp Cdng thuong, Tong quan thi trudng trang<br /> - 191,7 trieu USD. Nam 2008, ed 53 qudc gia x u i t<br /> thiit bj Y te. Tap chi Thong tin Thwang mai, (2008),<br /> khiu TTB y t i vao Viet Nam, tdng gia trj nhap Sd ra thang 10 nam 2008<br /> khiu dat 209,5 trieu USD, tang 5,6%o so vdi nam 2. Bd Y t i , Nghien ciru che tao va san xult trang<br /> 2007. Nhat Ban v i n d i n d i u v i kim ngaeh x u i t thiit bj y t i Ha Ndi, NXB Y hgc (2005)<br /> khiu TTB y t i vao Viet Nam, ehiim tren 16%> thj 3. Bd Y te, Ky yeu hdi nghj trien khai chinh sach<br /> phin. Trong dd san xuit trong nude mdi dap qudc gia ve TTB y t i giai doan 2004-2008, Ha Ndi,<br /> irng dugc khoang 40% nhu c i u sir dung va mdi (2008).<br /> <br /> <br /> <br /> N g h i e n e u ' U . . . (Tiip theo trang 23)<br /> 7. R.P.Raffin et al, Gastro-resistant microparticles 9. T.Comoglu et al. Development and in vitro<br /> containing sodium pantoprazole: Stability studies and evaluation of pantoprazole-loaded micropheres. Drug<br /> in vivo anti-ulcer activity, The Open Dnig J., (2007), 1, Del., 15, p. 295-298, (2008).<br /> p. 28-35. 10. Wei He et al. Influences of sodium carbonate<br /> 8. R.P.Raffin et al, Pharmacokinetics evaluation of on physicochemical properties of lanzoprazole in<br /> soft agglomerates for prompt delivery of enteric designed multiple coating pellets, AAPS<br /> pantoprazole-loaded microparticles, Eur J. Phanri. PharmSciTech., inpress, (2010).<br /> Biophamn., 74, p.275-280, (2010).<br /> <br /> <br /> TAP CHi DUOC HOC - 12/2010 (SO 416 NAM 50) 13<br />