塞普沙辛製劑之體外研究及生物藥劑分類系統免除生體相等性試驗初探   全文下載

In Vitro Testing of Ciprofloxacin Formulations and Preliminary Study on BCS Biowaiver

本文研究目的是比較塞普沙辛（ciprofloxacin）錠劑之品管及檢視其在生物藥學分類系統（BCS）之免除生體相等性試驗（biowaiver）的可行性。塞普沙辛是一種合成的?諾酮（quinolone）類廣效型抗生素，亦是生物藥學分類系統的第三類藥物。第二類及第三類的免除生體相等性試驗藥物有時須要科學驗證，塞普沙辛在pH 值6 以下具有高溶離度，而高於pH 值6 時其溶離度變差，因此性質介於第二類及第三類之間。比較10 種屬性相同及新品牌製劑的粉碎度、硬度、平均重量、含量均一性、崩散度及溶離度後，發現某些廠牌塞普沙辛的體外試驗其硬度、崩散度及溶離度有明顯差異。但所有廠牌的溶離度測試均符合藥典規定。然而，在0.1N 鹽酸溶液和磷酸緩衝溶液（pH 6.8）其溶離度有明顯的變化，而在醋酸緩衝溶液（pH 4.5）並沒有明顯變化。實驗結果推測可能是因為藥品的配方以及（或者）製造過程影響溶離度及生物可用率，而所觀察到的體外試驗差異也必須藉由體內生物等效研究加以確認。

The purpose of this study was to compare the technical quality of ciprofloxacin tablets and examine the feasibility of biopharmaceutical classification system (BCS) biowaiver. Ciprofloxacin is a synthetic quinolone derivative anti-infective agent that has been classified as a Class 3 substance according to the biopharmaceutics classification system. Due to the importance of ciprofloxacin as an antibiotic for widely resistant bacteria and the importance of price in a community basis, different ciprofloxacin products available on the market were analyzed. The possibility of extending biowaivers to ciprofloxacin was also examined. Waiver for Class 2 and Class 3 drugs is sometimes scientifically justified. Ciprofloxacin has properties that are intermediate between BCS Classes 2 and 3, as the drug is highly soluble below pH 6 and poorly soluble above this pH. Ten generic brands and the innovator brand were compared on friability, hardness, average weight, content uniformity, disintegration and dissolution. In vitro testing indicates significant variations among some brands in terms of hardness, disintegration and dissolution. Dissolution testing met pharmacopeial requirements for all brands. However, significant variations in dissolution profiles were observed in 0.1N HCl and in phosphate buffer (pH 6.8) with no difference detected in acetate buffer (pH 4.5). The results suggest that the formulation and/or the manufacturing process affect the dissolution and thus the bioavailability of the drug products. The significance of the observed in vitro differences must be confirmed by an in vivo bioequivalence study.