Formulation development and characterization of highly water-soluble drug-loaded extended-release pellets prepared by extrusion-spheronization technique
Formulation development and characterization of highly water-soluble drug-loaded extended-release pellets prepared by extrusion-spheronization technique
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DOI：
10.1007/s11998-019-00211-8
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发表时间：
2019-09-01
影响因子：
2.3
通讯作者：
Anwer, Sohail
中科院分区：
文献类型：
--
作者：
Nasiri, Muhammad Iqbal;Yousuf, Rabia Ismail;Anwer, Sohail
当前研究的目标是（a）通过挤出和滚圆技术制备盐酸伊托必利（ITP）的缓释普通（不含聚合物）和骨架微丸，（b）通过使用乙基纤维素、Eudragit（R）RL/RS100（2:1）和Kollicoat（R）SR包衣来控制药物从骨架微丸中的初始快速释放 30D，和（c）研究不同类型和浓度的包衣聚合物对高水溶性药物释放的影响。普通丸剂含有微晶纤维素和乳糖，不含聚合物，而基质丸剂配方由羟丙基甲基纤维素（HPMC K4M、K15M 和 K100M）和乙基纤维素（EC 7 cps）组成。基质微丸制剂未能控制药物释放，达 12 小时的目标时间。筛选出五种颗粒配方，一种不含聚合物 (F1)，一种来自每种聚合物类别（F4、F7、F10 和 F13），用于使用不同类型和水平的聚合物进行包衣。 DDSolver（MS Excel 的附加软件）用于分析药物释放动力学的溶出曲线数据。然而，含有 HPMC 作为基质形成剂并涂有 EC 的微丸制剂 (F7) 的药物释放遵循零级动力学 (R-2 = 0.897-0.998)。 EC包衣制剂F7、F10和F13的释放机制是非菲克扩散（异常传输），而F1和F4是菲克扩散机制。所有 5% EC 包衣的 ITP 微丸制剂的稳定性研究均按照 ICH 指南在室温和加速温度下进行，结果令人满意。结论是，除了Eudragit (R) RL/RS100 (2:1) 和Kollicoat (R) SR 30D 之外，乙基纤维素是一种优异的ITP 控释剂，具有良好的控释特性。
The objectives of current study were (a) to prepare extended-release plain (without polymers) and matrix pellets of itopride hydrochloride (ITP) by extrusion and spheronization technique, (b) to control the initial fast release of drug from the matrix pellets by coating using ethylcellulose, Eudragit (R) RL/RS100 (2:1), and Kollicoat (R) SR 30D, and (c) to investigate the influence of different types and concentration of coating polymers on release of highly water-soluble drug. The plain pellet contained microcrystalline cellulose and lactose without polymer, whereas matrix pellet formulations were composed of hydroxypropyl methylcellulose (HPMC K4M, K15M, and K100M) and ethylcellulose (EC 7 cps). Matrix pellet formulations failed to control the drug release, up to targeted period of 12 h. Five pellet formulations-one without polymer (F1) and one from each polymer category (F4, F7, F10, and F13)-were screened out for coating using different types and levels of polymers. The DDSolver (an add-in software for MS Excel) was used to analyze the dissolution profile data for drug release kinetics. However, drug release from pellet formulation (F7) containing HPMC as a matrix former and coated with EC followed zero-order kinetics (R-2 = 0.897-0.998). The release mechanism of EC-coated formulations F7, F10, and F13 was non-Fickian diffusion (anomalous transport), whereas F1 and F4 were Fickian diffusion mechanism. The stability studies of all 5% EC-coated ITP pellet formulations were conducted at room and accelerated temperature as per ICH guidelines, and results were found satisfactory. It is concluded that ethylcellulose other than Eudragit (R) RL/RS100 (2:1) and Kollicoat (R) SR 30D was found to be an excellent release controlling agent for ITP which showed good controlled-release characteristics.