Title:It is Possible to Achieve Tablets With Good Tabletability From Solid Dispersions – The Case of the High Dose Drug Gemfibrozil
VOLUME: 17
Author(s):Eduarda Rocha Bigogno, Luciano Soares, Matheus Henrique Ruela Mews, Melissa Zétola, Giovana Carolina Bazzo, Hellen Karine Stulzer and Bianca Ramos Pezzini*
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
Keywords:Gemfibrozil, solid dispersion, tabletability, tablet, drug dissolution, solubility.
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.
