Bristol-Myers Squibb, 1 Squibb Dr. New, Brunswick, NJ 08901, United States.
Bristol-Myers Squibb, Reeds Lane, Moreton Merseyside CH46 1QW, UK.
Int J Pharm. 2020 Jun 15;583:119343. doi: 10.1016/j.ijpharm.2020.119343. Epub 2020 Apr 17.
Controlled release tablets are important dosage forms enabling a slower release of the drug and better pharmacokinetics for some drugs and hydrophilic matrix tablets utilizing hydroxypropyl methylcellulose (HPMC) are one of the most common types. One of the main challenges with using HPMC is its poor flow when implemented in a direct compression process or when utilized for continuous manufacturing for which novel grades of direct compression have been developed. In this work, three different direct compression (DC) grades of HPMC (K4M, K15M and K100M) were characterized and compared to their standard grade (CR) counterparts. These materials were compared in terms of density, particle size, morphology, surface area and powder flow using multiple techniques. Results showed that the materials were almost identical in terms of particle shape and although the DC grades had better flow, the particle size was slightly smaller with an unexpectedly higher surface area, which most likely resulted from the inclusion of co-processed silicon dioxide in the DC grades. The bulk, tapped and true densities were slightly higher for all of the DC grades. Of the eleven different parameters used to characterize the flow of the materials the DC grades showed better flow than their standard CR counterparts for nine of the parameters (Carr's Index, Erweka flow, FT4 Flow Rate Index, Mean Avalanche Time, Avalanche Scatter, Number of Avalanches, Shear Cell Uni-axial Compressive Strength and Shear Cell Flow Function Coefficient). Only the FT4 Basic Flowability Energy and Specific Energy showed the opposite trend which can be explained from the testing methodology. It is recommended to evaluate the DC grades of HPMC for processes where better flowing material would have an advantage, such as direct compression, continuous manufacturing, and roller compaction if the powder flow into the rolls is problematic.
控释片剂是一种重要的剂型，可使药物释放速度更慢，某些药物的药代动力学更好。利用羟丙基甲基纤维素（HPMC）的亲水基质片剂就是最常见的类型之一。在直接压片工艺中使用 HPMC 时，主要面临的挑战之一是其流动性差，或者在连续制造中使用时，需要开发新型的直接压片等级。在这项工作中，对三种不同的直接压片（DC）等级的 HPMC（K4M、K15M 和 K100M）进行了表征，并与标准等级（CR）的 HPMC 进行了比较。使用多种技术比较了这些材料的密度、粒径、形态、表面积和粉末流动性。结果表明，这些材料在颗粒形状方面几乎相同，尽管 DC 等级的流动性更好，但粒径略小，表面积出乎意料地更高，这很可能是由于 DC 等级中包含了共处理的二氧化硅。所有 DC 等级的堆密度、振实密度和真密度都略高。在用于表征材料流动性的十一个不同参数中，对于九个参数，DC 等级的流动性优于其标准 CR 对应物（卡尔指数、Erweka 流动度、FT4 流动速率指数、平均雪崩时间、雪崩分散度、雪崩次数、剪切细胞单轴压缩强度和剪切细胞流动函数系数）。只有 FT4 基本流动性能量和比能量显示出相反的趋势，这可以从测试方法学中得到解释。建议在需要更好流动材料的工艺中评估 HPMC 的 DC 等级，例如直接压片、连续制造和辊压，如果粉末进入辊子时存在问题。
