Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
J Pharm Sci. 2010 Apr;99(4):1639-53. doi: 10.1002/jps.21954.
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 doxycycline hyclate are reviewed. According to the Biopharmaceutics Classification System (BCS), doxycycline hyclate can be assigned to BCS Class I. No problems with BE of IR doxycycline formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bioinequivalence caused by these factors appears to be low. Doxycycline has a wide therapeutic index. Further, BCS-based dissolution methods have been shown to be capable of identifying formulations which may dissolve too slowly to generate therapeutic levels. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing doxycycline hyclate as the single Active Pharmaceutical Ingredient (API) provided that (a) the test product contains only excipients present in doxycycline hyclate IR solid oral drug products approved in the International Conference on Harmonization (ICH) or associated countries; and (b) the comparator and the test products comply with the BCS criteria for "very rapidly dissolving" or, alternatively, when similarity of the dissolution profiles can be demonstrated and the two products are "rapidly dissolving.".
审查了与决定允许放弃体内生物等效性（BE）测试以批准含有盐酸多西环素的即时释放（IR）固体口服剂型的批准相关的文献数据。根据生物药剂学分类系统（BCS），盐酸多西环素可被归类为 BCS 类别 I。据报道，含有不同赋形剂和采用不同生产方法的 IR 多西环素制剂的 BE 没有问题，因此这些因素引起的生物等效性风险似乎很低。多西环素有很宽的治疗指数。此外，基于 BCS 的溶解方法已被证明能够识别可能溶解速度太慢而无法产生治疗水平的配方。结论是，对于含有盐酸多西环素作为唯一活性药物成分（API）的 IR 固体口服剂型，可以进行生物豁免，前提是：(a) 测试产品仅包含在国际人用药品注册协调会议（ICH）或相关国家批准的盐酸多西环素 IR 固体口服药物产品中存在的赋形剂；(b) 比较剂和测试产品符合“速溶”的 BCS 标准，或者可以证明溶解曲线的相似性，并且两种产品都是“速溶”。
