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It is Possible to Achieve Tablets With Good Tabletability From Solid Dispersions – The Case of the High Dose Drug Gemfibrozil

Author(s):

Eduarda Rocha Bigogno, Luciano Soares, Matheus Henrique Ruela Mews, Melissa Zétola, Giovana Carolina Bazzo, Hellen Karine Stulzer and Bianca Ramos Pezzini*   Pages 1 - 11 ( 11 )

Abstract:


Background: Solid dispersions (SDs) have been extensively used to increase 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.

Method: SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as 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.

Keywords:

Gemfibrozil, solid dispersion, tabletability, tablet, drug dissolution, solubility.

Affiliation:

Programa de Pós-Graduação em Saúde e Meio Ambiente, Universidade da Região de Joinville, Joinville, Programa de Pós-Graduação em Saúde e Meio Ambiente, Universidade da Região de Joinville, Joinville, Departamento de Farmácia, Universidade da Região de Joinville, Joinville, Departamento de Farmácia, Universidade da Região de Joinville, Joinville, Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis



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