Szoleczky Réka, Budai-Szűcs Mária, Csányi Erzsébet, Berkó Szilvia, Tonka-Nagy Péter, Csóka Ildikó, Kovács Anita
Egis Pharmaceuticals Plc., Laboratory of Finished Product Analytical Development 3, Bökényföldi Str. 116-120, 1165 Budapest, Hungary.
Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös Str. 6, 6720 Szeged, Hungary.
Pharmaceutics. 2022 Mar 26;14(4):707. doi: 10.3390/pharmaceutics14040707.
The aim of our study was to adapt the analytical quality by design (AQbD) approach to design an effective in vitro release test method using USP apparatus IV with a semi-solid adapter (SSA) for diclofenac sodium hydrogel. The analytical target profile (ATP) of the in vitro release test and ultra-high-performance liquid chromatography were defined; the critical method attributes (CMAs) (min. 70% of the drug should be released during the test, six time points should be obtained in the linear portion of the drug release profile, and the relative standard deviation of the released drug should not be over 10%) were selected. An initial risk assessment was carried out, in which the CMAs (ionic strength, the pH of the media, membrane type, the rate of flow, the volume of the SSA (sample amount), the individual flow rate of cells, drug concentration %, and the composition of the product) were identified. With the results, it was possible to determine the high-risk parameters of the in vitro drug release studies performed with the USP apparatus IV with SSA, which were the pH of the medium and the sample weight of the product. Focusing on these parameters, we developed a test protocol for our hydrogel system.
我们研究的目的是采用质量源于设计（AQbD）方法，设计一种有效的体外释放测试方法，该方法使用带有半固体适配器（SSA）的美国药典（USP）装置IV来检测双氯芬酸钠水凝胶。定义了体外释放测试的分析目标轮廓（ATP）和超高效液相色谱法；选择了关键方法属性（CMA）（测试期间至少70%的药物应释放，在药物释放曲线的线性部分应获得六个时间点，释放药物的相对标准偏差不应超过10%）。进行了初步风险评估，确定了CMA（离子强度、介质pH值、膜类型、流速、SSA体积（样品量）、细胞个体流速、药物浓度%和产品组成）。根据结果，可以确定使用带有SSA的USP装置IV进行的体外药物释放研究的高风险参数，即介质pH值和产品样品重量。围绕这些参数，我们为水凝胶系统制定了测试方案。
