利用複因子試驗設計法探討 Ramipril 膠囊之處方研究

A Study on Formulation of Ramipril Capsules by Factorial Experiment Method

陳九如(Chiu-Ju Chen)

指導教授 ： 詹道明

高雄醫學大學/藥學院/藥學研究所/碩士(2004年)

摘要

Ramipril是一種具降血壓效能的「血管緊縮素轉化脢抑制劑」。它用於治療高血壓、心衰竭，並改善心衰竭病人之心肌梗塞。本實驗利用複因子試驗設計法來找出最適合ramipril快速釋放膠囊的處方。
本實驗將探討自製處方與原廠處方在ramipril膠囊製備、含量均一度、安定性及溶離曲線圖的差異。二因子的三階試驗設計法將以ramipril膠囊釋出的百分比為依據，並以ANOVA來分析檢定變因。體外溶離試驗是依據USP 23的第一法來進行。膠囊的溶離及含量均一度是利用HPLC來分析的。膠囊貯存在不同的溫度及溼度下，以便檢測安定性。
試驗設計法證明prejel與溶媒pH值，對ramipril膠囊釋出有顯著的影響。在高溫貯存膠囊時，會使ramipril膠囊的含量明顯減少。自製處方與原廠處方皆有符合藥典對含量均一度的要求。自製處方與原廠處方的溶離曲線圖，將以相似因子法來評估二者的差異。
本實驗的結果指出，當處方含有高劑量的prejel，且在溶媒pH值為7.4時，會與原廠的處方有相似的溶離曲線圖。

關鍵字

相似因子 ； 試驗設計法

並列摘要

Ramipril is an active inhibitor of angiotensin converting enzyme with antihypertensive activity. It is used in the treatment of all forms of hypertension, heart failure, and following myocardial infarction to improve survival in patients with clinical evidence of heart failure. A statistical factorial experimental design was used to optimize the formulation of immediate-release ramipril capsules.
The ramipril capsules properties, uniformity content, storage effects, and dissolution profile, were studied and then compared to those of the innovator’s product. A three-level factorial design was employed to evaluate the effects of the two factors on the percentage release of ramipril; the subsequent data was compared using analysis of variance (ANOVA). In-vitro drug release test of the ramipril capsules was performed according to the USP 23 apparatus 1. The concentration of the dissolution solution and uniformity content of the capsules were assayed using a HPLC method. Storage effects at various temperatures and relative humidity on the stability of the formulations were also studied.
The experimental design study illustrated that prejel and pH value of the media had significant effect on the release percentage of ramipril capsules determined. A higher storage temperature showed a significant degradation effect on the ramipril capsules. It was found that the qualities of the innovator’s product met the pharmacopoeia requirements. The similarity factor (f2) between innovator’s product and the formulated samples was employed to compare their similarity, and satisfactory results were obtained.
These preliminary results indicate that to mimic the release profile of the innovator’s product by incorporating a higher percentage of prejel in pH 7.4 is possible.

並列關鍵字

similarity factor ； ramipril ； experimental design

參考文獻

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