- 學位論文
Propranolol長期釋放製劑之製備與評估
Preparation and Evalution of Propranolol Hydrochloride Extended Release Dosage Form
摘要
中文摘要 本研究目的為設計發展出一種Propranolol間質型長期控釋劑型（Propranolol extended-release matrices tablet）。 利用體外溶離試驗探討影響藥物釋出的因素包括：HPMC的黏度種類（4000 cps、30000 cps、15000 cps、100000 cps）、Drug/HPMC的比例（5/1、3/1、1/1.5、1/2）、Avicel的含量、潤滑劑的含量（0.5 %、1 %、2 %）以及製程的改變如：製備錠劑的方法（濕粒法、直接壓錠法）、壓錠的施力（100-200 kg/cm2）。 另外，利用Response surface methodology (RSM)之技術及二次多項式方程式，在多目標（藥物釋出百分率在第1.5，4，8，14，24小時，分別為：不可大於25 %，35-50 %，55-70 %，75-90 %，95-110 %。）的合適化技術下得到一合適化處方。其中以Drug/HPMC的比例與Avicel的含量設為independent factor，各時間點的藥物釋出百分率為dependent factor。 結果顯示，利用Response surface methodology (RSM)所得的合適化處方經由體外溶離試驗後藥物溶離曲線與預期的溶離曲線相符合。Propranolol自間質型長期釋放錠中之釋出機轉近似於Fickian diffusion。 經動物口服吸收試驗評估後，本實驗自製之Propranolol間質型長期釋放錠（Propranolol extended-release matrices tablet）的Cmax值較市售Propranolol速效錠低，MRT較長，顯示自製配方確實具有長期釋出之效果。而且亦有良好的體外/體內實驗藥物相關性存在（r＝0.996）。
並列摘要
英文摘要 Abstract The purpose of this study was to design and develop a Propranolol extended-release matrices tablets. The effects of viscosity of HPMC including 4000 cps, 30000 cps, 15000 cps, 100000 cps, Drug/HPMC ratio（5/1, 3/1, 1/1.5,）, amount of Avicel, lubricant level （0.5 %、1 %、2 %）, compaction pressure （100 kg/cm2, 130 kg/cm2, 200 kg/cm2）and so on were evaluated by the in vitro dissolution test. In addition, the response surface methodology (RSM) and multiple responses optimization utilizing quadratic polynomial equation were used to search for the optimal formulation with at 1.5, 4, 8, 14, and 24 hr were not more that 25 %, 35-50 %, 55-70 %, 75-90 % and 95-110 %, respectively. The drug/HPMC ratio and Avicel level were used as independent factor, and the release percents at different time interveral were used as dependent factor. The results showed that the optimized formulation provided dissolution pattern equivalent to the predicted curve which indicated that the which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HPMC matrices tablets followed quasi-Fickian diffusion. In vivo study, the Cmax was reduced and the MRT was prolonged for the Propranolol extended-release tablets. Furthermore, linear relationship between in vitro dissolution and in vivo absorption study was observed in the beagle dogs.