Brazilian Health Surveillance Agency, Anvisa, Division of Bioequivalence, Brasilia, Brazil.
J Pharm Sci. 2012 Jan;101(1):10-6. doi: 10.1002/jps.22756. Epub 2011 Sep 15.
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 stavudine (d4T) are reviewed. According to Biopharmaceutics Classification System (BCS), d4T can be assigned to BCS class I. No problems with BE of IR d4T 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. Furthermore, d4T has a wide therapeutic index. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing d4T as the single active pharmaceutical ingredient (API) provided that (a) the test product contains only excipients present in the IR d4T drug products that have been approved in a number of countries for the same dosage form, and (b) both test product and its comparator are either "very rapidly dissolving" or "rapidly dissolving" with similarity of dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8.
审查了与豁免体内生物等效性（BE）测试以批准含有司他夫定（d4T）的即时释放（IR）固体口服剂型的决定相关的文献数据。根据生物药剂学分类系统（BCS），d4T 可归类为 BCS 类别 I。尚未报道含有不同赋形剂和采用不同生产方法的 IR d4T 制剂的 BE 问题，因此，这些因素引起的生物等效性风险似乎较低。此外，d4T 的治疗指数很宽。结论是，对于含有 d4T 作为单一活性药物成分（API）的 IR 固体口服剂型，可以采用生物豁免，前提是（a）测试产品仅包含已在多个国家批准用于相同剂型的 IR d4T 药物产品中的赋形剂，并且（b）测试产品及其参比制剂均为“速溶”或“快速溶解”，在 pH 值为 1.2、4.5 和 6.8 时显示出相似的溶出曲线。
