Roy Harekrishna, Brahma Chandan K, Nandi Sisir, Parida Kirti R
Department of Pharmatechnology, Vikas College of Pharmaceutical Sciences, Suryapet, Nalgonda, Andhra Pradesh, India.
Int J Appl Basic Med Res. 2013 Jan;3(1):55-63. doi: 10.4103/2229-516X.112242.
The current paper was an attempt to design a sustained release dosage form using various grades of hydrophilic polymers, Hypromellose (hydroxyl-propyl methylcellulose [HPMC] K15M, HPMC K100M and HPMC K200M) and Polyacrylate polymers, Eudragit RL100 and Eudragit RS100 with or without incorporating ethyl cellulose on a matrix-controlled drug delivery system of Metformin hydrochloride.
Laboratory scale batches of nine tablet formulations were prepared by wet granulation technique (Low shear). Micromeritic properties of the granules were evaluated prior to compression. Tablets were characterized as crushing strength, friability, weight variation, thickness, drug content or assay and evaluated for in-vitro release pattern for 12 h using Phosphate buffer of pH 6.8 at 37 ± 0.5°C. The in-vitro release mechanism was evaluated by kinetic modeling.
The results obtained revealed that HPMC K200M at a concentration of 26% in formulation (F6) was able to sustain the drug release for 12 h and followed the Higuchi pattern quasi-Fickian diffusion. With that, combined effect of HPMC K15M as an extragranular section and Eudragit RS100 displayed a significant role in drug release. Dissolution data were compared with innovator for similarity factor (f2), and exhibited an acceptable value of ≥50 Three production validation scale batches were designed based on lab scale best batch and charged for stability testing, parameters were within the limit of acceptance. There was no chemical interaction found between the drug and excipients during Fourier Transform Infrared Spectroscopy (FTIR) and Differential scanning calorimetry study.
Hence, combinely HPMC K200M and Eudragit RS100 at a suitable concentration can effectively be used to sustain drug release.
本论文旨在尝试使用不同等级的亲水性聚合物、羟丙甲纤维素（羟丙基甲基纤维素[HPMC] K15M、HPMC K100M和HPMC K200M）以及聚丙烯酸酯聚合物、Eudragit RL100和Eudragit RS100，在含或不含乙基纤维素的情况下，为盐酸二甲双胍设计一种基质控制型药物递送系统的缓释剂型。
采用湿法制粒技术（低剪切）制备了实验室规模的九种片剂配方批次。在压片前对颗粒的粉体学性质进行了评估。片剂的特征包括抗压强度、脆碎度、重量差异、厚度、药物含量或含量测定，并在37±0.5°C下使用pH 6.8的磷酸盐缓冲液评估12小时的体外释放曲线。通过动力学模型评估体外释放机制。
所得结果表明，制剂（F6）中浓度为26%的HPMC K200M能够使药物释放持续12小时，并遵循Higuchi模式准Fickian扩散。在此基础上，HPMC K15M作为颗粒外部分与Eudragit RS100的联合作用在药物释放中发挥了重要作用。将溶出数据与参比制剂进行相似性因子（f2）比较，显示出≥50的可接受值。基于实验室规模的最佳批次设计了三个生产验证规模批次并进行稳定性测试，各项参数均在可接受范围内。在傅里叶变换红外光谱（FTIR）和差示扫描量热法研究中，未发现药物与辅料之间存在化学相互作用。
因此，将HPMC K200M和Eudragit RS100以合适的浓度联合使用可有效用于维持药物释放。
