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美洛昔康自纳米乳化颗粒(SNEGs):制备、表征、分子模拟及体内抗炎活性评价

Self nanoemulsifying granules (SNEGs) of meloxicam: preparation, characterization, molecular modeling and evaluation of in vivo anti-inflammatory activity.

作者信息

Parekh Vidhi J, Desai Namita D, Shaikh Mushtaque S, Shinde Ujwala A

机构信息

a Department of Pharmaceutics , Bombay College of Pharmacy, Kalina, Santacruz (E) , Mumbai , India.

b Department of Pharmaceutical Analysis , Bombay College of Pharmacy, Kalina, Santacruz (E) , Mumbai , India.

出版信息

Drug Dev Ind Pharm. 2017 Apr;43(4):600-610. doi: 10.1080/03639045.2016.1275665. Epub 2017 Jan 17.

Abstract

Meloxicam, a BCS class II drug belonging to the class of NSAIDs is indicated in conditions of rheumatoid arthritis, ankylosing spondylitis and osteoarthritis in which rapid onset of drug action is desired to reduce inflammation and pain. The objective of the study was to thus develop Self Nanoemulsifying Granules (SNEGs) of Meloxicam (MLX) for enhancement of solubility; and subsequently dissolution rate, thus aiming for a faster onset of action. Preliminary studies along with molecular modeling studies were carried out for selection of appropriate lipids, surfactants and cosurfactants for the development of MLX-loaded Self Nanoemulsifying preconcentrate (SNEP). A charge inducer was incorporated into the formulation so as to increase the solubility of MLX in lipids and hence, drug loading. A three-factor D-optimal mixture design was used for optimization of MLX loaded SNEP. The role of charge inducer in increasing the drug loading of MLX in SNEDDS was studied by molecular dynamics simulation using Desmond. Optimized SNEP was adsorbed onto solid carriers to form SNEGs for improved stability and enhanced flow properties. Physical characterization studies of SNEGs, in vitro release studies, and in vivo evaluation of anti-inflammatory activity of the optimized formulation were performed. All the results indicated that MLX SNEGs can be a promising alternative to conventional oral NSAIDs therapy because of enhanced dissolution characteristics and subsequent rapid onset of action.

摘要

美洛昔康是一种属于非甾体抗炎药(NSAIDs)类别的BCS II类药物,适用于类风湿性关节炎、强直性脊柱炎和骨关节炎等病症,在这些病症中需要药物作用快速起效以减轻炎症和疼痛。因此,本研究的目的是开发美洛昔康(MLX)的自纳米乳化颗粒(SNEGs)以提高溶解度;进而提高溶出速率,从而实现更快的起效。为了开发载有MLX的自纳米乳化预浓缩物(SNEP),进行了初步研究以及分子建模研究,以选择合适的脂质、表面活性剂和助表面活性剂。将电荷诱导剂加入到制剂中,以增加MLX在脂质中的溶解度,从而提高药物载量。采用三因素D-最优混合设计对载有MLX的SNEP进行优化。使用Desmond通过分子动力学模拟研究了电荷诱导剂在增加SNEDDS中MLX药物载量方面的作用。将优化后的SNEP吸附到固体载体上以形成SNEGs,以提高稳定性并增强流动性。对SNEGs进行了物理表征研究、体外释放研究以及对优化制剂的体内抗炎活性评估。所有结果表明,由于溶出特性增强以及随后起效迅速,MLX SNEGs可能是传统口服NSAIDs疗法的一个有前景的替代方案。

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