{"title":"The comparison of melt technologies based on mesoporous carriers for improved carvedilol dissolution","authors":"Mila Kovačević , Amrit Paudel , Odon Planinšek , Serena Bertoni , Nadia Passerini , Ožbej Zupančič , Carolina Alva , Ilija German Ilić , Alenka Zvonar Pobirk","doi":"10.1016/j.ejps.2024.106880","DOIUrl":null,"url":null,"abstract":"<div><p>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<sup>Ⓡ</sup> 244FP or Neusilin<sup>Ⓡ</sup> US2), which were loaded with carvedilol dispersed in polymeric matrix (polyethylene glycol 6000 or Soluplus<sup>Ⓡ</sup>). 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).</p><p>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<sup>Ⓡ</sup> 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.</p></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"202 ","pages":"Article 106880"},"PeriodicalIF":4.3000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0928098724001921/pdfft?md5=d5a7208da037d9bc0988e7329e9db7b5&pid=1-s2.0-S0928098724001921-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0928098724001921","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
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.
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
