| 英文摘要 |
The characteristics of FDA's similarity factor (f2) are investigated and compared with those of the time-series approach proposed by Chow and Ki for the comparison of dissolution profiles. The results indicate FDA's similarity factor simply reflects the overall average difference in percent dissolved of drug, regardless of the different pattern of dissolution. It should be noted, however, that the percent dissolved data in the profile are highly correlated time-series data; they are not the independent variables that the FDA's method assumed. Moreover, the asymptote is usually reached within 45 minutes of dissolution for most of the immediate release solid dosage form products. A high f2 value can be manipulated if one includes several more data points at the asymptote to overcome the large differences observed in 15 to 45 minutes dissolution. Thus, the true difference in dissolution characteristics of the two products may be distorted. Although the f2 method has the advantage of simplicity, it lacks strict statistical justification. On the other hand, the time-series approach proposed by Chow and Ki is much more powerful in discerning differences in dissolution pattern between two drug products. However, Chow and Ki's method does not consider cases with a declined cumulative dissolution profile.
藥品的生體可用率特性為確保藥物治療之有效性及安全性之重要品質，各國皆經由法規之制訂加以嚴格管理。然而對同一廠商在優良藥品製造規範（cGMP）之管制下所生產的不同批次之同一製劑或生產配方或產程上有些微次要的變更者，允許以溶離曲線之比對代替昂價費時的人體試驗作為品質確保的方便方法。美國FDA公布溶離曲線比對的基準，但所用之類同度之意義曖昧，被認為有統計學上及藥劑學上之疑慮。本報告針對FDA之類同度以及Chow and Ki所提倡的時間數列解析法，以實例加以剖析檢討。結果顯示FDA類同度法雖然簡易，但不能反映溶離曲線真實的差異。時間數列解析法雖然比較靈敏能區別溶離曲線形的差異性，但對溶解度隨溶離時間減少之弱酸或弱鹼鹽類藥物之溶離曲線之比對無法使用。在缺少合理可靠的溶離曲線比對方法以及溶離特性和生體可用率尚無明確的相關性之狀態下，以簡陋的FDA類同度作為溶離曲線的比對方法而省略人體生體可用率及生體相等性試驗，必須相當的謹慎。 |
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