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방출 실험 방법에 따른 Propranolol·HCI-Polyvinyl alcohol hydrogel Hollow type 좌제로부터의 약물방출 특성

Title
방출 실험 방법에 따른 Propranolol·HCI-Polyvinyl alcohol hydrogel Hollow type 좌제로부터의 약물방출 특성
Other Titles
Release profiles of propranolol·HCl from PPH-PVA hydrogel hollow type suppository using various release tests
Authors
宋美沃
Issue Date
1994
Department/Major
대학원 약학과
Keywords
방출실험PropranololHCI약물방출
Publisher
이화여자대학교 대학원
Degree
Master
Abstract
좌제로부터의 방출 및 토끼 직장 흡수를 실험하고 in vitro-in vivo의 상관관계를 가지는 방출 실험법을 찾기 위하여, model drug으로 수용성인 Propranolol·HCl (PPH)을 사용하고 기제로는 Polyvinyl alcohol(PVA)hydrogel을 사용하여 PPH 원말을 중공부에 봉입시킨 중공좌제와 기제에 약물을 분산시킨 통상형 좌제를 제조하였다. 제조된 좌제를 Paddle method, Muranishi method 및 Dialysis tubing method의 3가지 방출 실험법으로 방출 용매량과 교반속도를 변화시키면서 좌제로부터의 약물 방출 양상을 관찰한 결과 교반속도와 방출 용매량의 변화에는 별로 영향을 받지 않았다. 통상형에 비해 중공좌제는 초기에 방출 지연 양상을 나타내었으나 시간의 경과에 따라 방출 속도가 빨라져서 24시간에는 통상형과 거의 같은 누적 방출량을 나타낸다. 방출 실험 방법에 따라 방출 양상의 차이를 보이는데 Paddle method는 24시간에 거의 전량 방출되나 Dialysis tubing method나 Muranishi method에서는 70-90%정도 약물이 방출되어 방출량에 차이를 보였다. 좌제의 토끼 직장 투여 후 중공좌제의 t_(max)는 통상형에 비해 지연되었고 C_(max)는 낮았으나 4시간부터는 통상형보다 높은 혈중 농도를 나타내었고 AUC_(0-8)는 중공좌제가 통상형의 1.6배 이상이었다. 이는 방출실험에서의 중공좌제 및 통상형 좌제로부터 방출 패턴과 유사하였다.;In order to study release and absorption in rabbits of drug from the suppository and to find release test collelated with the in vivo-in vitro, a hollow type suppository containing PPH powder in the cavity and a dispersing drug conventional type suppository in the base were prepared using Polyvinyl alcohol(PVA) hydrogel as a base and water-soluble PropranololㆍHCI(PPH) as a model drug. Drug release from the prepared suppositories were measured by three different type of method, Paddle method, Muranishi method and Dialysis tubing entyod in 400, 500 and 900ml volume of pH 7.4 Phosphate Buffer and at 50, 100rpm of stirring rate. As a result of studying on release profile for chaging volume of pH 7.4 Phosphate Buffer and stirring rate from suppositories, both stirring rate and volume of mdeium had a little effect. As compared with a conventional type suppository, a hollow type suppository showed a sustained period of initial release phase but as time goes by release rate was getting faster that hollow type suppository reached almost same as cumulative released amount in 24-hour. According to various release test, the release profile showed difference. paddle method had almost released out in 24-hour but Dialysis tubing or Muranishi method had about 70-90% drug released. After a rectal adminstration in rabbit, the of hollow type suppository was more sustained than conventional type suppository. It agreed to the result of high initial relase from conventional type suppository in release test. But from 4-hour plasma concentration was higher than conventional type suppository and AUC_(0-8) was more than 1.6 times than those of conventional type suppository.
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