Department of Pharmaceutical Sciences, Industrial Pharmacy Research Group, University of Basel, Mulhauserstrasse, Basel, Switzerland.
Drug Dev Ind Pharm. 2012 Jun;38(6):697-705. doi: 10.3109/03639045.2011.623166. Epub 2011 Oct 19.
The aim of this study was to develop a high-dose tablet formulation of the poorly soluble carbamazepine (CBZ) with sufficient tablet hardness and immediate drug release. A further aim was to investigate the influence of various commercial CBZ raw materials on the optimized tablet formulation.
Hydroxypropyl cellulose (HPC-SL) was selected as a dry binder and crospovidone (CrosPVP) as a superdisintegrant. A direct compacted tablet formulation of 70% CBZ was optimized by a 3² full factorial design with two input variables, HPC (0--10%) and CrosPVP (0--5%). Response variables included disintegration time, amount of drug released at 15 and 60 min, and tablet hardness, all analyzed according to USP 31.
Increasing HPC-SL together with CrosPVP not only increased tablet hardness but also reduced disintegration time. Optimal condition was achieved in the range of 5--9% HPC and 3--5% CrosPVP, where tablet properties were at least 70 N tablet hardness, less than 1 min disintegration, and within the USP requirements for drug release. Testing the optimized formulation with four different commercial CBZ samples, their variability was still observed. Nonetheless, all formulations conformed to the USP specifications.
With the excipients CrosPVP and HPC-SL an immediate release tablet formulation was successfully formulated for high-dose CBZ of various commercial sources.
本研究旨在开发高剂量的卡马西平（CBZ）片剂，使其具有足够的片剂硬度和即刻药物释放。进一步的目的是研究不同商业 CBZ 原料药对优化片剂配方的影响。
选择羟丙纤维素（HPC-SL）作为干粘合剂，交联聚维酮（CrosPVP）作为超级崩解剂。通过 3² 全因子设计，以 HPC（0-10%）和 CrosPVP（0-5%）为两个输入变量，对 70% CBZ 的直接压片配方进行优化。响应变量包括崩解时间、15 分钟和 60 分钟时的药物释放量以及片剂硬度，所有这些都根据 USP31 进行分析。
HPC-SL 与 CrosPVP 一起增加不仅增加了片剂的硬度，还缩短了崩解时间。在 5-9% HPC 和 3-5% CrosPVP 的范围内达到了最佳条件，片剂性能至少为 70N 片剂硬度、崩解时间小于 1 分钟，并且符合 USP 对药物释放的要求。用四种不同的商业 CBZ 样品测试优化的配方，仍然观察到它们的可变性。尽管如此，所有配方均符合 USP 规格。
使用 CrosPVP 和 HPC-SL 这两种赋形剂，成功地为各种商业来源的高剂量 CBZ 开发了即刻释放片剂配方。
