Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brasilia, Brazil.
J Pharm Sci. 2011 May;100(5):1618-27. doi: 10.1002/jps.22409. Epub 2011 Jan 19.
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing metronidazole are reviewed. Metronidazole can be assigned to Biopharmaceutics Classification System Class I. Most BE studies that were identified reported the investigated formulations to be bioequivalent, indicating the risk of bioinequivalence to be low. Formulations showing differences in bioavailability showed dissimilarities in in vitro dissolution profiles. Furthermore, metronidazole has a wide therapeutic index. It is concluded that a biowaiver for solid IR formulations is justified, provided: (a) the test product and its comparator are both rapidly dissolving; (b) meet similarity of the dissolution profiles at pH 1.2, 4.5, and 6.8; (c) the test product contains only excipients present in IR drug products approved in International Conference on Harmonisation (ICH) or associated countries in the same dosage form; and (d) if the test product contains sorbitol, sodium laurilsulfate, or propylene glycol, the test product needs to be qualitatively and quantitatively identical to its comparator with respect to these excipients [corrected]..
审查了与决定允许豁免体内生物等效性 (BE) 测试以批准含有甲硝唑的即时释放 (IR) 固体口服剂型的批准相关的文献数据。甲硝唑可归入生物药剂学分类系统 I 类。大多数确定的 BE 研究报告表明所研究的制剂具有生物等效性，表明生物不等效的风险较低。显示生物利用度差异的制剂显示出体外溶解曲线的差异。此外，甲硝唑具有较宽的治疗指数。结论是，对于固体 IR 制剂，可以进行生物豁免，前提是：(a) 测试产品及其参比制剂均快速溶解；(b) 在 pH 值 1.2、4.5 和 6.8 下，溶解曲线具有相似性；(c) 测试产品仅包含在国际人用药品注册技术协调会 (ICH) 或相关国家批准的 IR 药物产品中存在的赋形剂，且 (d) 如果测试产品含有山梨糖醇、月桂基硫酸钠或丙二醇，则测试产品需要在这些赋形剂方面与参比制剂在定性和定量上完全相同[已更正]。
