目的 在口服固體制劑仿制藥體外溶出相似性評價研究中，針對批內(nèi)溶出量相對標(biāo)準(zhǔn)偏差（RSD）較大、無法滿足相似因子（f₂）法適用條件的情況，驗(yàn)證非模型依賴多變量置信區(qū)間法在溶出曲線相似性評價中的使用區(qū)別。方法 參考FDA和CFDA發(fā)布的《口服固體制劑溶出度試驗(yàn)技術(shù)指導(dǎo)原則》，使用兩種不同的非模型依賴多變量置信區(qū)間法，即Bootstrap統(tǒng)計(jì)驗(yàn)證方法（BS）和Mahalanobis distance多變量分析法（MD）對模擬的參比制劑與仿制制劑溶出數(shù)據(jù)相似性進(jìn)行評價。結(jié)果 利用BS法得出仿制批與參比批的f₂預(yù)期值（f₂^*）=59.965，大于50。MD法得到參比批次間多變量統(tǒng)計(jì)矩最大值是1.559 4，并將其確定為相似性限度，仿制批與參比批多變量置信區(qū)間90%上限為2.656 7，大于相似限度。結(jié)論 采用BS法評價體外溶出具備相似性，而采用MD評價方法則不具備相似性。因此，對于同一組數(shù)據(jù)，選用不同的評價方式可能會得出不同的結(jié)論。

Objective In the study of evaluation of consistency for in vitro dissolution of oral solid dosage forms of generics, we verified the differences of non-model dependent multivariable confidence interval method for evaluating the similarity of dissolution profiles in the case of with significantly different in within-batch dissolution profile RSD which was unable to apply f₂ approach. Method According to Guidance for Industry:Immediate Release Solid Oral Dosage Forms (released by FDA and CFDA), we used two different model independent multivariate confidence region procedure, i.e. Bootstrap statistical verification method (BS) and Mahalanobis distance multivariable analysis method (MD), to evaluate the similarity of dissolution data of reference product and generic product. Results For BS, the f₂^* is 59.965, f₂^*>50. For MD, the maximum of inter-batch multivariable statistic moment of reference product is 1.559 4, indicated that the reference product and generic product had similar quality. However, the inter-batch 90% upper limits between reference drug and generic drug was 2.656 7, which was larger than similar limit. Conclusion It was showed that reference product and generic product were similar when BS method was used. In contrast, MD method indicated that they were different. Therefore, different evaluation methods may result in contrary conclusions for the same data.