Improvement of the Dissolution Behavior of the Poorly Water Soluble Drug Diacerein by Solid Dispersion Technology and its Formulation into Tablet Dosage Form

Abstract

Diacerein (DAC) is an antiarthritic drug that shows almost negligible water solubility in acidic conditions and gets degraded at alkaline pH which restricts its oral bioavailability. The degradation product also leads to soft stool effect. The aim of the present study was to enhance the dissolution rate of DAC by solid dispersion (SD) technology and to incorporate the best SD formula (the one which is able to promote the highest drug release in minimum period of time) into tablet dosage form. Various binary (containing DAC and polyethylene glycols i.e. PEGs) and ternary (containing DAC, PEG and a pH modulating agent) SD formulations were prepared employing different process and formulation parameters. SDs so prepared were investigated for the dissolution behavior of DAC. The best SD formulation was characterized by aqueous solubility studies, XRD, ATR, SEM and DCS studies. A series of tablet dosage forms containing the best SD formula as the drug matrix was prepared using different concentrations of disintegrating agent. The best tablet (the one that allows the maximum disintegration in minimum period of time) was compared with the marketed preparation according to compendial specifications. All binary and ternary formulations increased drug dissolution rate. Dissolution studies show that there is a trend of increasing dissolution rate of DAC with decreasing molecular weight of PEGs as well as decreasing percentage of DAC in the SDs. Ternary SDs show higher dissolution in comparison to binary SDs, reflecting synergism of PEG4000 with urea. DAC solubility increased 3.39 times by the best SD formula. Physical characterization revealed the changes in solid state (decreased crystallinity) of DAC during the formation of SD. The best SD formula loaded tablet gave significantly higher dissolution compared to commercial product, which indicates its potential for delivering poorly water soluble drug DAC with enhanced bioavailability and reduced soft stool effects.