高分子材質的水性分散液製備包覆顆粒之研究
Preparation of coated granules using ploymeric aqueous dispersion
中文摘要
本研究主要在於評估探討利用高分子材質的水性分散液, 以濕式造粒法 planetary 形式的攪拌造粒機中製備藥物的包覆顆粒或結晶之可行性評估的影響因素可分 為製程條件和處方成份. 其中的製程條件包括有高分子材質的水性分散液的傾倒 速度和攪拌造粒機之轉速. 而處方方面評估的包括塑化劑的用量, 分散液的濃度 及黏度等,其影響性將以溶離特定百分比所需時間作比較標準的包覆效率為主要 評估基準. 並同時測定包覆顆粒的物化性質,包括有流動性, 密度, 和粒度分佈等.
進而將所得的包覆顆粒混合不同賦形劑而壓製成間質性錠片, 期能篩選出能賦予 錠片控釋效果的賦形劑種類和用量, 其中也將評估不同壓錠力對此錠片控釋的影 響性.由實驗結果顯示,攪拌機轉速較小者,包覆效率較好. 處方中高分子聚
合物的含量愈高,包覆效率愈好,而壓錠力對藥物釋放效率不具影響性, 其決定因 素在於藥物本身之溶解度. 酒精的添加無法改善包覆效果必須藉助於賦形劑的加 入才可延緩藥物的釋放. 至於藥物釋放機轉則以適當的數學模式加以探討, 結果 符合 Hiquchi equation.
英文摘要
The main objective of this study is to evaluate the potential possibility of Wet- granulating drug particles into coated granules in a planetary-typer Mixer using polymeric aqueous dispersion as a gran- ulating agent. The factors evaluated can be divided into the process and formulation variables. In this study,the process variables that have been examined include the pouring rate of aqueous dispersion and stirring rate. The formulation variables that have been studied include the additional amount of plas- ticizer, and the polymer content in aqueous disper- sion and its viscosity ect..The extent of influence of these factors have been judged mainly based on the coating efficiency, which is indicated by the dissolution time need for certain fraction being released. Simultaneously,the physical properties of coated granules, including flowability, bulk and tapped densities and size distribution ect., have been tested. Furthermore, coated granules have been compressed into matrix tablets after mixing with excipients. Hopfully,the kind of excipients and its used amount, which building into the tablets with desired controlled-release property,can be screened.
Moreover, the effects of compression pressure on the controlled-release characters of the tablets have been evaluated and been used as a reference to screen the formulation for the matrix tablets. The results indicated that slower stirring rate ,larger amount of polymer in the formulation would result in better coating efficiency.The compression pressure did not affect the drug release rate. It is determined by the drug solubility
itself. The addition of alcohol in the formulation could not improve coating efficiency.
Drug release could be delayed by adding excipients. As for drug release mechchanism, could be described to by Hiquchi equation transport model.
