Abstract

The aim of present work was to improve physicochemical properties of model drug Chlorzoxazone by crystallo-co-agglomeration (CCA) in the presence of different polymers and excipients. Identification of Quality Target Product Profile and Critical Quality Attributes were done using Risk assessment and Failure mode effect analysis. CCA was formulated by applying Box–Behnken design followed by principal component analysis (PCA). CCA was further studied for its topographical, micromeritic, mechanical, compressional, and dissolution properties. Prepared CCA showed improvement in flow and packability with rich drug content (90.84%). Heckel parameters indicated greater plastic deformation (K = 0.8132) and tensile strength compared to the pure drug (K = 19.256 kg/cm²). CCA showed negligible elastic recovery (0.87%) compared to the pure drug (5.708%). Dissolution of the drug was increased to 2.69-folds compared to the pure drug after 60 min. No degradation or polymorphic transformation of the drug was observed even after stability study (40 °C, 75% RH). The amount of directly compressible diluents could be minimized in tablet formulation, which was a considerable improvement in the properties of the drug for making directly compressible form. The study highlights an improvement of processing characteristics of Chlorzoxazone by CCA using an integrated approach of QbD and PCA.

摘要

目前工作的目的是在不同聚合物和赋形剂的存在下通过晶体共聚结 (CCA) 改善模型药物氯唑沙宗的理化性质。使用风险评估和失效模式影响分析确定质量目标产品概况和关键质量属性。CCA 是通过应用 Box-Behnken 设计然后进行主成分分析 (PCA) 来制定的。进一步研究了 CCA 的形貌、微观、机械、压缩和溶解特性。制备的 CCA 表现出流动性和可包装性的改善，药物含量丰富 (90.84%)。Heckel 参数表明 与纯药物相比具有更大的塑性变形 ( K = 0.8132) 和拉伸强度 ( K  = 19.256 kg/cm ²）。与纯药物 (5.708%) 相比，CCA 显示出可忽略不计的弹性恢复 (0.87%)。60 分钟后，与纯药物相比，药物的溶出度增加到 2.69 倍。即使经过稳定性研究（40 °C，75% RH），也没有观察到药物的降解或多晶型转化。在片剂配方中可将直接可压缩的稀释剂的量减至最少，这对于制备可直接压缩形式的药物的性质是相当大的改进。该研究强调了使用 QbD 和 PCA 的集成方法通过 CCA 改进氯唑沙宗的加工特性。