Nurhikmah Wilda, Sumirtapura Yeyet Cahyati, Pamudji Jessie Sofia
School of Pharmacy Bandung Institute of Technology, Ganesha 10, 40132, Bandung, Indonesia.
Sci Pharm. 2016 Feb 14;84(1):181-90. doi: 10.3797/scipharm.ISP.2015.09. Print 2016 Jan-Mar.
Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial methods available for dissolution tests of mefenamic acid solid dosage forms, i.e. methods of United States Pharmacopeia 37 (USP) and Pharmacopoeia of the People's Republic of China 2010 (PPRC). Indonesian Pharmacopeia V ed. (FI) adopted the USP method. On the other hand, many researches focused on the use of a 'biorelevant' medium to develop the dissolution test method. The aim of this research was to study the dissolution profile of mefenamic acid from its solid dosage forms (caplet and capsule) available in the Indonesian market with three different dissolution medium: USP, PPRC, and biorelevant fasted simulated small intestinal fluid (FaSSIF) media. The tested products consisted of the innovator's product (available only in caplet dosage form, FN caplet) and generic products (available as caplet and capsule). The dissolution test of the drug products in all dissolution media was performed in 900 mL of medium using apparatus II (paddle) at a temperature of 37°C and rotation speed of 75 rpm, except for the capsule product and for USP medium, both of which tests were done using apparatus I (basket) with rotation speed of 100 rpm. The solubility test of mefenamic acid was carried out in all media at temperature of 37°C. The result obtained from the solubility test showed that the the highest solubility of mefenamic acid was obtained in USP medium (approximately 2 mg/mL), followed by PPRC medium (about 0.5 mg/mL), and FaSSIF medium (approximately 0.06 mg/ml). In the dissolution test, percentage of drug dissolved in in the USP and PPRC media after 45 min for all products reached more than 75%, except for the PN caplet in USP medium which reached only about 44%. Meanwhile, in the biorelevant medium, the percentage of drug dissolved for all products did not exceed 16%. In all dissolution media, the capsule dosage form achieved the highest dissolution rate.
甲芬那酸是一种非甾体抗炎药（NSAID），广泛用于治疗轻至中度疼痛。甲芬那酸属于生物药剂学分类系统（BCS）中的II类药物，其水溶性较低但渗透性较高。有两种不同的药典方法可用于甲芬那酸固体剂型的溶出度测试，即美国药典37版（USP）方法和中华人民共和国药典2010年版（PPRC）方法。印度尼西亚药典第V版（FI）采用了USP方法。另一方面，许多研究集中在使用“生物相关”介质来开发溶出度测试方法。本研究的目的是研究甲芬那酸在印度尼西亚市场上的固体剂型（胶囊和软胶囊）在三种不同溶出介质中的溶出曲线：USP、PPRC和生物相关的禁食模拟小肠液（FaSSIF）介质。受试产品包括创新产品（仅以胶囊剂型提供，FN胶囊）和仿制药产品（以胶囊和软胶囊形式提供）。除胶囊产品和USP介质外，所有溶出介质中药物产品的溶出度测试均在900 mL介质中使用装置II（桨）在37°C温度和75 rpm转速下进行，这两种测试均使用装置I（篮）在100 rpm转速下进行。甲芬那酸的溶解度测试在所有介质中于37°C温度下进行。溶解度测试结果表明，甲芬那酸在USP介质中的溶解度最高（约2 mg/mL），其次是PPRC介质（约0.5 mg/mL）和FaSSIF介质（约0.06 mg/mL）。在溶出度测试中，所有产品在USP和PPRC介质中45分钟后药物溶解百分比均超过75%，但USP介质中的PN胶囊仅达到约44%。同时，在生物相关介质中，所有产品的药物溶解百分比均未超过16%。在所有溶出介质中，胶囊剂型的溶出速率最高。
