Department of Pharmaceutical Technology, Gülhane Military Medical Academy, Ankara, Turkey.
Pharm Dev Technol. 2013 Sep-Oct;18(5):1122-30. doi: 10.3109/10837450.2012.710240. Epub 2012 Aug 13.
Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.
盐酸甲氧氯普胺(MTC)常用于治疗胃肠道疾病。它的生物半衰期较短,通常每天给药四次,以维持全天有效的浓度。本研究旨在开发药物的亲水基质缓释片剂制剂,以实现可重复和可预测的释放率、延长的作用持续时间、降低毒性、减少所需剂量、优化治疗和提高患者依从性。羟丙甲纤维素(HPMC)、羧甲基纤维素钠(NaCMC)、壳聚糖和 Carbopol 981 分别或组合作为释放控制因子通过直接压缩技术被加入到基质系统中。通过 DSC 和 FTIR 分析评估制剂成分之间的相容性。通过美国药典溶出仪 II 评估 MTC 从基质中的释放。所有制剂均符合药典要求。溶出度研究表明,聚合物类型和浓度是影响药物释放的重要参数。壳聚糖、Carbopol 和 NaCMC 制剂表现出 pH 依赖性药物释放特性,而 HPMC 则没有。所有含有 HPMC 和壳聚糖 1:1 比例的制剂均表现出理想的药物释放,表明所有活性物质在整个溶出时间内逐渐释放,因此可以考虑将其用于制造 MTC 缓释产品。