脂质和纤维素基质成型剂对挤出/球形化、烧结和压缩颗粒中高溶性药物释放的影响。

Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.

Faculty of Pharmacy, Jinnah University for Women, Karachi, 74600, Pakistan.

出版信息

Lipids Health Dis. 2018 Jun 9;17(1):136. doi: 10.1186/s12944-018-0783-8.

DOI:10.1186/s12944-018-0783-8

PMID:29885655

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5994249/

Abstract

BACKGROUND

The study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol using hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control the release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular diseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl monostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were used in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control the burst release of Atenolol.

METHOD

For this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology (RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes (GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were performed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order, first order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of DDsolver, an excel based add-in program.

RESULTS

The formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model (R = 0.975-0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy showed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The cross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that the optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug release for 12 h.

CONCLUSION

Extended-release encapsulated, and compacted pellets were successfully prepared after the combination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in addition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is an effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.

摘要

背景

本研究旨在开发一种阿替洛尔的延长释放（ER）包衣和压缩颗粒，使用疏水性（基于蜡和聚合物的）和高粘度级亲水性基质成型剂，通过挤出/球形化（ES）控制这种高水溶性药物的释放。阿替洛尔用于心血管疾病，有即时释放（IR）片剂剂型。脂质、巴西棕榈蜡（CW）、单硬脂酸甘油酯（GMS）和纤维素基，即羟丙基甲基纤维素（HPMC）和乙基纤维素（EC），用于制备阿替洛尔 ER 颗粒。热烧结和压缩技术也被应用于控制阿替洛尔的突释。

方法

为此，使用响应面法（RSM）通过 Design-Expert 10 软件设计了 36 种试验配方（F1-F36），以 HPMC K4M、K15 M 和 K100 M、EC 7FP、10FP 和 100FP、蜡（GMS 和 CW）及其组合、烧结温度和时间作为输入变量。在 pH 1.2、4.5 和 6.8 的溶解介质中进行了溶出度研究。使用不同的模型，如零级、一级、Korsmeyer-Peppas、Hixon Crowell、Baker-Lonsdale 和 Higuchi 动力学，通过 DDsolver，一个基于 excel 的插件程序，研究了药物释放动力学。

结果

配方 F35 和 F36 在 pH 4.5 的溶解介质中符合 Korsmeyer-Peppas 超案例 II 传递模型（R=0.975-0.971）。FTIR 未观察到药物赋形剂相互作用。立体显微镜显示，烧结组合颗粒（F35）高度球形（AR=1.061，球形度=0.943）。F34 和 F35 的横截面 SEM 放大倍数（7000X）显示出密集的交联。结果表明，优化后的配方为 F35（烧结颗粒）和 F36（压缩颗粒），能有效控制 12 小时的药物释放。