Zhang Xiaofei, Gu Xiangqin, Wang Xiaodan, Wang Huimin, Mao Shirui
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Asian J Pharm Sci. 2018 Nov;13(6):566-574. doi: 10.1016/j.ajps.2018.01.004. Epub 2018 Mar 2.
The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride (VH) as a drug model, the feasibility of using chitosan (CS), carbomer (CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS-CBM matrix tablets were investigated. It was found that CS-CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), in situ self-assembled polyelectrolyte complex (PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in Beagle dogs, with level A and correlation (IVIVC) established successfully. In conclusion, CS-CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.
本研究的目的是采用基质技术设计缓释片，其能够很好地控制高水溶性药物的释放，具有良好的系统稳健性且制备工艺简单。以盐酸文拉法辛（VH）作为药物模型，研究了使用壳聚糖（CS）、卡波姆（CBM）组合系统实现该目标的可行性。研究了影响CS - CBM基质片药物释放的处方和工艺变量。结果发现，CS - CBM组合系统减弱了CS、CBM材料性质以及胃排空时间对药物释放曲线的潜在影响。通过直接观察、差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）证明，在胃肠道转运过程中，片剂表面形成了原位自组装聚电解质复合物（PEC）膜，这有助于对药物释放进行可调节且稳健的控制。在比格犬体内进一步证明了药物的缓释行为，并成功建立了A级体内外相关性（IVIVC）。总之，CS - CBM基质片是一种有前景的系统，可调节和控制高水溶性药物的释放，且具有良好的系统稳健性。
