Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn Campus, 75 DeKalb Avenue, Room WL 313, Brooklyn, New York, NY, 11201, USA.
Triclinic Labs, 2660 Schuyler Ave Ste A, Lafayette, IN, 47905, USA.
AAPS PharmSciTech. 2020 Jun 12;21(5):172. doi: 10.1208/s12249-020-01702-3.
Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components. To overcome these challenges, standard and uniform working practices are required that are not only helpful in preparation of stable FeSSGF but also serve as a harmonizing guide for the collection of dissolution/solubility samples and their subsequent processing (i.e., handling and assay). The optimization of sample preparation methodology is crucial to reduce method-related variance by ensuring specificity, robustness, and reproducibility with acceptable recovery of the analytes. The sample preparation methodology includes a combination of techniques including filtration, solvent treatment, and centrifugation to remove the interfering media-related components and excipients from the analyte. The analytes of interest were chromatographically separated from the interfering analytes to quantify the drug concentration using the new high-performance liquid chromatography methods with ultraviolet detection. The methods developed allow rapid sample preparation, acceptable specificity, reproducible recoveries (greater than 95% of label claim), and quantification of study drugs (ibuprofen and ketoconazole). The sample preparation technique and method considerations provided here for ibuprofen and ketoconazole can serve as a starting point for solubility and dissolution testing of other small molecules in FeSSGF.
在制药行业，从新产品的早期开发到预测生物等效性，不同生物相关介质中的溶解测试和溶解度测定都引起了相当大的兴趣。在所有生物相关流体中，制备进食状态模拟胃液（FeSSGF）以及处理溶解/溶解度测试中来自 FeSSGF 的样品被认为是相对具有挑战性的。挑战包括在采样、过滤时保持 FeSSGF 介质的稳定性，以及减轻赋形剂和牛奶成分的分析干扰。为了克服这些挑战，需要标准和统一的工作实践，这些实践不仅有助于制备稳定的 FeSSGF，而且还为收集溶解/溶解度样品及其随后的处理（即处理和分析）提供了协调指南。优化样品制备方法学对于通过确保分析物的特异性、稳健性和重现性以及可接受的回收率来减少方法相关的变异性至关重要。样品制备方法学包括各种技术的组合，包括过滤、溶剂处理和离心，以从分析物中去除干扰介质相关成分和赋形剂。感兴趣的分析物与干扰分析物进行色谱分离，使用新的高效液相色谱法（带有紫外检测）定量药物浓度。开发的方法允许快速进行样品制备，具有可接受的特异性、可重现的回收率（大于标签声称的 95%）以及研究药物（布洛芬和酮康唑）的定量。这里为布洛芬和酮康唑提供的样品制备技术和方法注意事项可以作为在 FeSSGF 中对其他小分子进行溶解度和溶解测试的起点。
