Nguyen H T, Shiu G K, Worsley W N, Skelly J P
Biopharmaceutics Research Branch, Food and Drug Administration, Washington, DC 20204.
J Pharm Sci. 1990 Feb;79(2):163-7. doi: 10.1002/jps.2600790217.
Dissolution of oral contraceptive combination products from six manufacturing firms was studied utilizing the rotating basket method at 100 rpm in 600 mL of 0.1 M HCl and 0.02% sodium lauryl sulfate (SLS). Most of the combination products of norethindrone (NE):ethinyl estradiol (EE) dissolved satisfactorily in water using the paddle method which was first proposed by U.S.P., whereas three of 18 tested products showed better dissolution in acidic aqueous medium containing SLS. Acidic medium with surfactant was also found to be suitable for combination products of norethindrone (NE):mestranol (ME) and norethindrone acetate (NEAc):ethinyl estradiol (EE). A modified U.S.P. assay procedure, a reversed-phase high-performance liquid chromatographic (HPLC) method with a mobile phase of acetonitrile and phosphate buffer, was used to analyze NE and EE concurrently. The NEAc and ME were analyzed separately in these combination products. The NEAc was found to hydrolyze to some extent (approximately 20% in 8 h) in acidic dissolution medium at room temperature, but less so at 4 degrees C. The NE was identified as the sole degradation product of NEAc hydrolysis and was also measured to account for the total amount of NEAc dissolved. A simple dissoluting testing method which utilizes a single dissolution medium was applicable for all oral contraceptive combination tablets surveyed.
采用转篮法，在转速为100转/分钟的条件下，于600毫升0.1M盐酸和0.02%十二烷基硫酸钠（SLS）中，对来自6家生产企业的口服复方避孕药产品进行溶出度研究。大多数炔诺酮（NE）：炔雌醇（EE）复方产品采用美国药典首次提出的桨法在水中溶出情况良好，而18种受试产品中有3种在含SLS的酸性水介质中溶出效果更好。还发现含表面活性剂的酸性介质适用于炔诺酮（NE）：美雌醇（ME）和醋酸炔诺酮（NEAc）：炔雌醇（EE）的复方产品。采用改良的美国药典分析程序，即使用乙腈和磷酸盐缓冲液作为流动相的反相高效液相色谱（HPLC）法，同时分析NE和EE。在这些复方产品中分别分析NEAc和ME。发现NEAc在室温下于酸性溶出介质中会有一定程度的水解（8小时内约20%），但在4℃时水解程度较小。NE被确定为NEAc水解的唯一降解产物，并且还测定了其占溶解的NEAc总量的比例。一种采用单一溶出介质的简单溶出度测试方法适用于所调查的所有口服复方避孕片片剂。
