좌제로부터의 약물의 방출제어에 관한 연구

Abstract

좌제로부터의 약물의 방출제어를 도모하기 위하여 Poly Vinyl Alcohol(PVA) hydrogel을 기제로 사용한 중공좌제를 제조하였다. model drug으로는 난용성 약물인 Indomethacin(IDM)을 사용하였으며 약물자제의 용출속도증가를 목적으로 Poly Vinyl Pyrrolidone(PVP)와 lactose를 carrier로 두종류의 Solid Dispersion System(SDS)를 제조하고 각각을 중공좌제의 중공부에 봉입하여 IDM-SDS중공좌제를 제조하였다. SDS의 용출실험결과에서 IDM-Lactose-SDS(1:2)및 IDM-PVP-SDS(1:1)의 1시간 누적 용출량은 IDM원말이 52%였음에 비해 각각 86%및 100%로 현저히 증가되었다. 분말 X-ray회전실험과 DSC의 결과에서 IDM-SDS는 원말의 결정성이 감소되었음을 확인할 수 있었다. 좌제로부터의 방출실험결과 IDM원말중공좌제의 24시간 누적방출량이 17%였음에 비해 IDM-Lactose-SDS를 봉입한 중공좌제및 IDM-PVP-SDS를 봉입한 중공좌제는 각각 57%및 51%로 IDM의 방출이 증대되었다. 또한 IDM 50mg에 해당하는 IDM-SDS의 반은 중공부에 봉입하고 반은 기제에 분산시킨 좌제(Type C)를 제조하여 초기방출및 누적 방출량을 증대시킬 수 있었다. IDM-Lactose-SDS와 IDM-PVP-SDS의 Type C좌제의 토끼직장 흡수실험결과 약물의 흡수는 지속적이었으나 in vitro에서의 약물방출과 다른 양상을 보였다.;In order to study the release control of drug from the suppository, the hollow type suppositories were prepared using PVA hydrogel as a base. Indomehtacin(IDM, poorly water soluble) was chosen as a model drug and for the improvement of IDM solubility, Two types of Solid Dispersion System(SDS) was prepared using Lactose and PVP as a carrier. Three types of hollow type suppositories were prepared with IDM-Lactose-SDS and IDM-PVP-SDS(Type B: SDS only in cavity, Type C:1/2 SDS in cavity and 1/2 SDS in base, Type D: 1/2 SDS in cavity and 1/2 IDM powder in base) and for the comparative study, a conventional suppository(Type A) and a hollow type suppository(Type B) with IDM powder were prepared. All suppositories contained 50mg as IDM. In vitro dissolution test of the SDS showed that the dissolved amount of IDM-Lactose-SDS and IDM-PVP-SDS for 1-hour were 86% and 100% respectively whereas that of IDM powder was 52%. In vitro release test from the suppositories showed that the released amount of Type B with IDM-Lactose-SDS or IDM-PVP-SDS for 24-hours were 3 and 3.5 times respectively compared with Type B with IDM powder. After a single rectal administration to rabbits, the AUC_(0->9) of Type with IDM powder and Type C with IDM-Lactose-SDS or IDM-PVP-SDS were 1508, 1009 and 730(㎍/ml/min) respectively and this result does not correspond with in vitro release characteristics.