High-shear wet granulation of SMEDDS based on mesoporous carriers for improved carvedilol solubility

Kovačević, Mila (author), German Ilić, Ilija (author), Bolko Seljak, Katarina (author), Zvonar Pobirk, Alenka (author)

Mesoporous carriers are a convenient choice for the solidification of self-microemulsifying drug delivery systems (SMEDDS) designed to improve the solubility of poorly water-soluble drugs. They are known for high liquid load capacity and the ability to maintain characteristics of dry, free-flowing powders. Therefore, five different mesoporous carriers were used for the preparation of carvedilol-loaded SMEDDS granules by wet granulation methods—in paten (manually) and using a high-shear (HS) granulator. Granules with the highest SMEDDS content (63% and 66% of total granules mass, respectively) and suitable flow properties were obtained by Syloid$^®$ 244FP and Neusilin$^®$ US2. SMEDDS loaded granules produced by HS granulation showed superior flow characteristics compared to those obtained manually. All SMEDDS granules exhibited fast in vitro release, with 93% of carvedilol releasing from Syloid$^®$ 244FP-based granules in 5 min. Upon compaction into self-microemulsifying tablets, suitable tablet hardness and very fast disintegration time were achieved, thus producing orodispersible tablets. The compaction slightly slowed down the carvedilol release rate; nevertheless, upon 1 h (at pH 1.2) or 4 h (at pH 6.8) of in vitro dissolution testing, the amount of released drug was comparable with granules, confirming the suitability of orodispersible tablets for the production of the SMEDDS loaded single unit oral dosage form.

• Language: English
• Keywords: SMEDDS, mesoporous carriers, wet granulation, high-shear granulator
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 21 str.
• Numbering: Vol. 14, iss. 10, art. 2077
• PID: 20.500.12556/RUL-141617
• UDC: 544.351.3:621.6.04
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics14102077
• COBISS.SI-ID: 123836163
• Publication date in RUL: 03.10.2022

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

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: SMEDDS, mezoporozni nosilci, mokra granulacija, visokostrižni granulator, granulat, topnost

Projects

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

• Funder: Other - Other funder or multiple funders
• Funding programme: Public Scholarship, Development, Disability and Maintenance Fund of Republic of Slovenia, Ad futura scholarship