Title:It is Possible to Achieve Tablets With Good Tabletability From Solid Dispersions – The Case of the High Dose Drug Gemfibrozil
VOLUME: 18 ISSUE: 4
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, Pharmaceutical Sciences Department, Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, Pharmaceutical Sciences Department, Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, Pharmaceutical Sciences Department, 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 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.
