Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA.
Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA; Pii Center for Pharmaceutical Technology, University of Mississippi, University, MS 38677, USA.
Eur J Pharm Sci. 2018 Aug 30;121:126-138. doi: 10.1016/j.ejps.2018.05.007. Epub 2018 May 14.
The current study's aim is to prepare lipid based sustained release tablets via a twin-screw granulation technique and compare those dosage forms with conventional techniques, namely wet granulation and direct compression. The granules were successfully manufactured in a single-step, continuous twin-screw granulation process with a low proportion of binder (Klucel™ EF, HPC SSL) using Compritol® 888 ATO, Precirol® ATO 5 and Geleol™ as sustained release agents. The granules prepared showed good flow characteristics and compaction properties. DSC and XRD studies were conducted to characterize the granules prepared via a twin-screw granulation method and the results demonstrated the crystalline nature of lipids within the granules. FTIR data indicated that there were no interactions with the formulation components investigated. The formulations developed by all three methods were compressed into tablets with a mechanical strength of 14-16 KP. The tablets formulated were characterized for physicochemical properties, in vitro drug release studies, water uptake and erosion studies. These results showed that the drug was not completely released after 24 h for tablets developed by the wet granulation process using all three lipids. The tablets prepared by the direct compression method demonstrated a burst release within 8 to 10 h from Precirol ATO 5® and Geleol™ formulations compared to Compritol® 888 ATO. However, tablets prepared using twin-screw granulation exhibited sustained release of the drug over 24 h and the water uptake and erosion results were in accordance with dissolution data. Stability data for 45 days at accelerated conditions (40 °C/75% RH) showed similar release profiles with ƒ2 values above 50 for all of the twin screw granulation formulations, indicating the suitability of the process for formulating sustained release tablets. These findings of a single-step, continuous twin-screw granulation process are novel and demonstrate new opportunities for development of sustained release tablets.
本研究旨在通过双螺杆造粒技术制备脂质型缓控释片剂，并将其与传统技术（即湿法制粒和直接压片）进行比较。采用低比例粘合剂（Klucel™ EF、HPC SSL），使用 Compritol® 888 ATO、Precirol® ATO 5 和 Geleol™ 作为缓控释剂，在一步法连续双螺杆造粒工艺中成功制备了颗粒。所制备的颗粒具有良好的流动特性和压缩性能。通过差示扫描量热法（DSC）和 X 射线衍射（XRD）研究对通过双螺杆造粒法制备的颗粒进行了表征，结果表明颗粒内的脂质具有结晶性。傅里叶变换红外光谱（FTIR）数据表明，与所研究的制剂成分之间没有相互作用。通过这三种方法制备的制剂均被压制成机械强度为 14-16 kPa 的片剂。对所制备的片剂进行了理化性质、体外药物释放研究、吸湿性和溶蚀性研究。这些结果表明，使用所有三种脂质的湿法制粒过程制备的片剂在 24 小时后药物未完全释放。与使用 Compritol® 888 ATO 相比，直接压片法制备的含有 Precirol ATO 5®和 Geleol™的片剂在 8 至 10 小时内表现出药物的突释。然而，通过双螺杆造粒法制备的片剂在 24 小时内持续释放药物，并且吸湿性和溶蚀性结果与溶出数据一致。在加速条件（40°C/75% RH）下 45 天的稳定性数据表明，所有双螺杆造粒制剂的释放曲线相似，ƒ2 值均高于 50，表明该工艺适合于制备缓控释片剂。这一单步连续双螺杆造粒工艺的研究结果是新颖的，为开发缓控释片剂提供了新的机会。
