在製藥工業上，口服控制釋放方面主要以間質性系統(Matrix system)、儲藏式系統(Reservoir system)和滲透壓幫浦系統(Osmotic pump system)三種作為依據，對於不同賦形劑在所設計的劑型中扮演的角色及其賦形劑本身所擁有的性質應與控制釋放劑型本身做結合，以達到劑型設計本身所需的控制釋放結果，對於本研究來說，運用所製成的間質性錠劑外圍包覆一層膜衣，其膜衣的擴散機制是控制藥物釋放速率的關鍵，在這些膜衣的性質中，聚合物膜的親疏水性和膨脹性質對於藥物釋放速率和擴散機制的影響最為顯著。
目前本研究將所使用的模式藥物阿夫唑秦鹽酸鹽運用直接打錠法製備間質性錠劑，而在間質性錠劑中以12.5%、25%和50%三種不同比例的羥丙基甲基纖維素(Hydroxyl Propyl Methyl Cellulose, HPMC)作為控制釋放材質，運用製備完成的間質性錠劑以不同親疏水性比例之聚乙烯吡咯烷酮(Poly Vinyl Pyrrolidone, PVP) /聚乙酸乙烯酯(Poly Vinyl Acetate, PVA)作為膜衣包覆處方的原料，再以3%和5%為膜衣包覆百分比，而運用薄膜的藥物滲透試驗和膜衣機械強度試驗作為不同親疏水性膜衣輸送機制及機械性質之探討，而所製備完成的膜衣包覆錠劑的溶離試驗方法依據美國藥典(USP)的槳式(Paddle)模式(900 ml溶離液，37 ± 0.5℃和100 rpm的轉速)。
研究結果顯示，在間質性錠劑中增加HPMC的添加量則會降低藥物溶離的速率和藥物釋放百分比，可能主要為藥物經羥丙基甲基纖維素吸水所形成之膠體層擴散而進行藥物控制釋放，而HPMC越多，形成之膠體層越大，藥物釋放路徑越長，進而達到較慢的藥物釋放速率。
對於間質性錠劑所包覆之膜衣而言，增加親水性高分子在膜衣包覆的比例中，則會增加藥物溶離的速率和藥物釋放百分比，主要為膜衣成份中之親水性高分子材料在包覆膜衣之錠劑進入溶離液後會形成孔隙，進而使水分進入錠劑，藉由藥物溶解後經擴散方式通過膜衣以及包覆錠劑內部之間質性錠劑主成分HPMC經吸水膨脹後將部分膜衣撐破兩種方式釋放藥物，由於膜衣的親疏水性的不同以及包覆錠劑內部的HPMC量不同而使得膜衣的撐破時間點、破裂程度和溶離液滲透性也不同，所以也就有不同程度的控制藥物釋放效果。 Three common oral controlled delivery systems including matrix, reservoir, and osmotic pump system are often used in the pharmaceutical field. The aim of this study is to investigate the performance and mechanism of different formulations of alfuzosin hydrochloride using matrix and matrix-coating system. Different excipients such as water swellable polymeric matrices have found broad application in controlled release system, and diffusion often controls the rate of drug release from the system. Therefore, in order to control drug release, characterization of the effects of the polymer blends and polymer swelling on drug release diffusion is crucial. In the present study, direct compression method was utilized to prepare matrix tablets. The amounts of hydroxyl propyl methyl cellulose (HPMC) in matrix and various amount of hydrophilic / hydrophobic polymers in matrix -coating membrane were studied to assess drug release characteristics. The coating membrane used were percentage of 3% and 5%. Drug permeability and mechanical properties of polymer membrane with different composition were determined. Dissolution tests were performed according to the USP paddle method (900 ml medium, 37 ± 0.5℃ and 100 rpm). For matrix tablets, the results indicate that drug release rates can be decreased by increasing amount of HPMC. Swelling results are also consistent with drug release results. Higher swelling and less erosion were observed for tablet with higher amount of HPMC. For matrix-coating systems, the results indicate that drug release rates can be decreased by increasing amount of hydrophobic polymers in polymer blend and coating percentage. The results demonstrate that controlled release of alfuzosin hydrochloride is feasible using matrix and matrix-coating system.
