The comparison of melt technologies based on mesoporous carriers for improved carvedilol dissolution

IF 4.3 3区医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-08-22 DOI:10.1016/j.ejps.2024.106880

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Abstract

High-shear (HS) melt granulation and hot melt extrusion (HME) were compared as perspective melt-based technologies for preparation of amorphous solid dispersions (ASDs). ASDs were prepared using mesoporous carriers (Syloid^Ⓡ 244FP or Neusilin^Ⓡ US2), which were loaded with carvedilol dispersed in polymeric matrix (polyethylene glycol 6000 or Soluplus^Ⓡ). Formulations with high carvedilol content were obtained either by HME (11 extrudates with polymer:carrier ratio 1:1) or HS granulation (6 granulates with polymer:carrier ratio 3:1).

DSC and XRD analysis confirmed the absence of crystalline carvedilol for the majority of prepared ADSs, thus confirming the stabilizing effect of selected polymers and carriers over amorphous carvedilol. HME produced larger particles compared to HS melt granulation, which was in line with better flow time and Carr index of extrudates. Moreover, SEM images revealed smoother surface of ASDs obtained by HME, contributing to less obstructed flow. The rougher and more porous surface of HS granules was correlated to larger granule specific surface area, manifesting in faster carvedilol release from Syloid^Ⓡ 244FP-based granules, as compared to their HME counterparts. Regarding dissolution, the two HS-formulations performed superior to pure crystalline carvedilol, thereby confirming the suitability of HS melt granulation for developing dosage forms with improved carvedilol dissolution.

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比较基于介孔载体的熔融技术，以改善卡维地洛的溶解。

比较了高剪切（HS）熔融造粒和热熔挤出（HME）这两种基于熔体的无定形固体分散体（ASDs）制备技术。使用介孔载体（Syloid® 244FP 或 Neusilin® US2）制备 ASD，将卡维地洛分散在聚合物基质（聚乙二醇 6000 或 Soluplus®）中。通过 HME（11 个挤出物，聚合物与载体的比例为 1:1）或 HS 造粒（6 个颗粒，聚合物与载体的比例为 3:1），获得了高卡维地洛含量的配方。DSC 和 XRD 分析证实，大多数制备的 ADS 中都没有结晶的卡维地洛，从而证实了所选聚合物和载体对无定形卡维地洛的稳定作用。与 HS 熔体造粒相比，HME 产生的颗粒更大，这与挤出物更好的流动时间和卡尔指数相符。此外，扫描电子显微镜图像显示，通过 HME 获得的 ASD 表面更光滑，从而减少了流动阻碍。HS 颗粒表面更粗糙、孔隙更多，因此颗粒比表面积更大，与 HME 颗粒相比，Syloid® 244FP 颗粒的卡维地洛释放速度更快。在溶出方面，两种 HS 制剂的表现均优于纯结晶的卡维地洛，从而证实了 HS 熔体制粒适用于开发可改善卡维地洛溶出的剂型。

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来源期刊

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.