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

Kovačević, Mila (author), Paudel, Amrit (author), Planinšek, Odon (author), Bertoni, Serena (author), Passerini, Nadia (author), Zupančič, Ožbej (author), Alva, Carolina (author), German Ilić, Ilija (author), Zvonar Pobirk, Alenka (author)

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.

• Language: English
• Keywords: mesoporous carrier, melt granulation, hot melt extrusion, PEG 6000, Soluplus, amorphous solid dispersion
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 13 str.
• Numbering: Vol. 202, [article no.] 106880
• PID: 20.500.12556/RUL-164728
• UDC: 661.12
• ISSN on article: 0928-0987
• DOI: 10.1016/j.ejps.2024.106880
• COBISS.SI-ID: 205524483
• Publication date in RUL: 08.11.2024

Record is a part of a journal

• Title: European Journal of Pharmaceutical Sciences
• Shortened title: Eur. j. pharm. sci.
• Publisher: Elsevier
• ISSN: 0928-0987
• COBISS.SI-ID: 17553413

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: mezoporozni nosilec, granulacija taline, ekstruzija vroče taline, PEG 6000, Soluplus, amorfna trdna disperzija, farmacevtska tehnologija, farmacevtske oblike

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0189
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih