Li Suye, Wu Hengqian, Zhao Yanna, Zhang Ruiyan, Wang Zhengping, Han Jun
College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China.
School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China.
Pharmaceutics. 2021 May 27;13(6):802. doi: 10.3390/pharmaceutics13060802.
The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% /. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.
药品生产过程中的质量控制至关重要，尤其是在生产过程中活性药物成分（API）中存在不同的多晶型形式，这可能会影响制剂产品的性能。本研究的目的是研究盐酸非索非那定（FXD）的相变及其对药物质量和性能的影响。在FXD的湿法制粒过程中，加水是从I型向II型（水合物）多晶型转变的关键控制因素。采用X射线衍射（XRD）和热分析对FXD的水致相变进行了研究和定量。当FXD与水混合时，它会迅速转变为II型，而当FXD与辅料一起制剂化时，转变会受到抑制。此外，当含水量<15%时，转变完全被抑制。在小规模研究了相变与含水量之间的关系，并且它也适用于湿法制粒过程中的放大生产。通过评估颗粒特性和溶出行为，研究了相变对FXD片剂性能的影响。结果表明，在转变过程中，溶解的FXD起到粘合剂的作用，改善颗粒的性质，如密度和流动性。然而，如果加水过多，可能会导致FXD在溶出过程中释放不完全。为了平衡颗粒的质量属性和溶出度，在湿法制粒过程中应控制FXD的相变和加入的水量。
