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.
Development of Fully Redispersible Dried Nanocrystals by Using Sucrose Laurate as Stabilizer for Increasing Surface Area and Dissolution Rate of Poorly Water-soluble Drugs
