Controlled Release of Gelucire-based Solid Dispersions Containing Poorly Water-Soluble Drug = Gelucire를 기초로 한 고체분산체(solid dispersion)의 난용성 약물의 제어 방출.

국문 초록 (Abstract)

Pranlukas(PLK)와 같은 난용성 약물은 낮은 용해도와 용출율을 보이고, 생체이용율도 낮아 제제상의 어려움이 있다. 본 실험에 서는 낮은 용출율을 개선하고, 적절한 제어방출 방법을 개발하 기 위하여, Gelucire44/14^(??) (GEL)를 바탕으로 한 PLK 고체분산체 에 4 가지 폴리머(PEO, HPMC, RSPO, Stearyl alcohol )를 섞어 용 융법(melting method)으로 조제하였다. 폴리머를 첨가하지 않은 PLK-GEL 고체분산체와 폴리머를 첨가한 고체분산체를 인공장 액(pH 6.8) 상에서 용출 실험을 실시하여, 약물의 제어 방출과 그에 따른 적절한 제형을 선택하였고, DSC 와 PXRD 를 이용하 여, 약물의 구조 변형을 평가하였다. 그 결과, 고체분산체에서 부분적인 무정형의 PLK 를 확인할 수 있었다. 특히, PEO 와 HPMC 를 이용한 PLK-GEL 고체분산체 제제는 제어방출을 조절 하는데 유용하게 응용될 것으로 기대된다.

다국어 초록 (Multilingual Abstract)

PLK, a poorly water-soluble drug (1.2㎍/ml H2O at 25℃) was selected as a model drug. Poor solubility is generally associated with poor dissolution characteristics and poor oral bioavailability. In order to improve these characteristics and to expulse controlled release system, Gelucire 44/14^(??)(GEL)-based solid dispersions of PLK with 4 kinds of polymers were manufactured by the melting method. Dissolution tests of GEL-based PLK solid dispersion were investigated to check proper polymer and formulation for controlled drug release. The structural behaviors of GEL-based PLK solid dispersion were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). It was shown that the drug existed partially amorphous in the solid dispersion. GEL-based PLK solid dispersion with PEO, HPMC could be applied to prepare the controlled release system of PLK.

목차 (Table of Contents)

• Abstract = 5
• 1. Introduction = 6
• 2. Materials and Methods = 10
• 2.1. Materials = 10
• 2.2. Solid dispersion and controlled release = 10
• 2.3. In vitro dissolution study = 11
• 2.4. Differential scanning calorimetry (DSC) = 12
• 2.5. Powder X-ray diffraction (PXRD) = 12
• 3. Results and Discussion = 15
• 3.1. Effect of GEL amount in solid dispersion = 15
• 3.2. Dissolution profile on various polymers = 17
• 3.3. Effect of PEO Dissolution of GEL-based solid dispersions capsule = 19
• 3.4. Dissolution profile on granule and capsule = 22
• 3.5. Physical characterization of GEL-based PLK solid dispersions = 27
• 4. Conclusion = 27
• 5. References = 28