Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Ipiranga 2752/402, 90610-000, Porto Alegre, RS, Brazil,
AAPS PharmSciTech. 2014 Feb;15(1):189-97. doi: 10.1208/s12249-013-0053-z. Epub 2013 Nov 22.
A dissolution method to analyze atorvastatin tablets using in vivo data for RP and test pilot (PB) was developed and validated. The appropriate conditions were determined after solubility tests using different media, and sink conditions were established. The conditions used were equipment paddle at 50 rpm and 900 mL of potassium phosphate buffer pH 6.0 as dissolution medium. In vivo release profiles were obtained from the bioequivalence study of RP and the generic candidate PB. The fraction of dose absorbed was calculated using the Loo-Riegelman method. It was necessary to use a scale factor of time similar to 6.0, to associate the values of absorbed fraction and dissolved fraction, obtaining an in vivo-in vitro correlation level A. The dissolution method to quantify the amount of drug dissolved was validated using high-performance liquid chromatography and ultraviolet spectrophotometry, and validated according to the USP protocol. The discriminative power of dissolution conditions was assessed using two different pilot batches of atorvastatin tablets (PA and PB) and RP. The dissolution test was validated and may be used as a discriminating method in quality control and in the development of the new formulations.
开发并验证了一种使用体内数据进行瑞舒伐他汀片剂分析的溶出度方法，用于反向压力（RP）和测试批次（PB）。在使用不同介质进行溶解度测试后，确定了适当的条件，并建立了沉降条件。所用条件为桨板设备，转速为 50rpm，900mL 磷酸钾缓冲液 pH6.0 作为溶出介质。从 RP 和仿制药候选 PB 的生物等效性研究中获得体内释放曲线。使用 Loo-Riegelman 方法计算吸收分数。为了将吸收分数和溶解分数的值联系起来，获得体内-体外相关性水平 A，有必要使用时间比例因子相似于 6.0。使用高效液相色谱法和紫外分光光度法对定量溶解药物量的溶出度方法进行了验证，并根据 USP 方案进行了验证。使用两种不同的阿托伐他汀片剂（PA 和 PB）和 RP 的两个不同的试验批次评估了溶出度条件的区分能力。溶出度试验得到验证，可用于质量控制和新制剂开发中的鉴别方法。
