School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Int J Pharm. 2013 Jun 25;450(1-2):197-207. doi: 10.1016/j.ijpharm.2013.04.052. Epub 2013 Apr 25.
The aim of this study was to better understand the underlying drug release characteristics from chitosan-alginate matrix tablets containing different types of drugs. Theophylline, paracetamol, metformin hydrochloride and trimetazidine hydrochloride were used as model drugs exhibiting significantly different solubilities (12, 16, 346 and >1000 mg/ml at 37 °C in water). A novel concept raised was that drugs were released from chitosan-alginate matrix tablets based on the theory of a self-assembled film-controlled release system. The film was only formed on the surface of tablets in gastrointestinal environment and originated from chitosan-alginate polyelectrolyte complex, confirmed by differential scanning calorimetry characterization. The formed film could decrease the rate of polymer swelling to a degree, also greatly limit the erosion of tablets. Drugs were all released through diffusion in the hydrated matrix and polymer relaxation, irrespective of the drug solubility. The effects of polymer level and initial drug loading on release depended on drug properties. Drug release was influenced by the change of pH. In contrast, the impact of ionic strength of the release medium within the physiological range was negligible. Importantly, hydrodynamic conditions showed a key factor determining the superiority of the self-assembled film in controlling drug release compared with conventional matrix tablets. The new insight into chitosan-alginate matrix tablets can help to broaden the application of this type of dosage forms.
本研究旨在更好地理解含不同类型药物的壳聚糖-海藻酸钠基质片剂的药物释放特性。茶碱、对乙酰氨基酚、盐酸二甲双胍和盐酸曲美他嗪被用作模型药物,它们的溶解度有显著差异(在 37°C 水中的溶解度分别为 12、16、346 和>1000mg/ml)。提出了一个新的概念,即药物是根据自组装膜控释系统理论从壳聚糖-海藻酸钠基质片剂中释放出来的。该膜仅在胃肠道环境中的片剂表面形成,源自壳聚糖-海藻酸钠聚电解质复合物,这通过差示扫描量热法表征得到证实。形成的膜可以在一定程度上降低聚合物的溶胀速率,也极大地限制了片剂的侵蚀。药物都是通过水合基质中的扩散和聚合物松弛释放的,与药物的溶解度无关。聚合物水平和初始药物载药量对释放的影响取决于药物的性质。药物释放受 pH 值变化的影响。相比之下,生理范围内释放介质的离子强度对药物释放的影响可以忽略不计。重要的是,水动力条件是决定自组装膜在控制药物释放方面优于传统基质片剂的关键因素。对壳聚糖-海藻酸钠基质片剂的新认识有助于拓宽这种剂型的应用。