It is Possible to Achieve Tablets With Good Tabletability From Solid Dispersions – The Case of the High Dose Drug Gemfibrozil
| Autor: | Melissa Zétola, Giovana Carolina Bazzo, Bianca Ramos Pezzini, Matheus Henrique Ruela Mews, Hellen Karine Stulzer, Luciano Soares, Eduarda Rocha Bigogno |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Croscarmellose sodium Chromatography Drug Compounding media_common.quotation_subject Pharmaceutical Science Factorial experiment Drug Liberation chemistry.chemical_compound Solubility chemistry Ultimate tensile strength medicine Gemfibrozil Dissolution testing Dissolution Tablets media_common medicine.drug |
| Zdroj: | Current Drug Delivery. 18:460-470 |
| ISSN: | 1567-2018 |
| Popis: | Background: Solid Dispersions (SDs) have been extensively used to increase the dissolution of poorly water-soluble drugs. However, there are few studies exploring SDs properties that must be considered during tablet development, like tabletability. Poorly water-soluble drugs with poor compression properties and high therapeutic doses, like gemfibrozil, are an additional challenge in the production of SDs-based tablets. Objective: This study evaluates the applicability of SDs to improve both tabletability and dissolution rate of gemfibrozil. A SD-based tablet formulation was also proposed. Methods: SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as a carrier, according to a 23 factorial design. The formulation variables were gemfibrozil:HPMC ratio, milling speed, and milling time. The response in the factorial analysis was the tensile strength of the compacted SDs. Dissolution rate and solid-state characterization of SDs were also performed. Results: SDs showed simultaneous drug dissolution enhancement and improved tabletability when compared to corresponding physical mixtures and gemfibrozil. The main variable influencing drug dissolution and tabletability was the gemfibrozil:HPMC ratio. Tablets containing gemfibrozil-HPMC-SD (1:0.250 w/w) and croscarmellose sodium showed fast and complete drug release while those containing the same SD and sodium starch glycolate exhibited poor drug release due to their prolonged disintegration time. Conclusion: SDs proved to be effective for simultaneously improving tabletability and dissolution profile of gemfibrozil. Tablets containing gemfibrozil-HPMC-SD and croscarmellose sodium as disintegrating agent showed improved drug release and good mechanical strength, demonstrating the potential of HPMC-based SDs to simultaneously overcome the poor dissolution and tabletability properties of this drug. |
| Databáze: | OpenAIRE |
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