Diacerein solid dispersion loaded tablets for minimization of drug adverse effects: statistical design, formulation, in vitro, and in vivo evaluation

Abstract

Diacerein is a BCS class II drug employed in osteoarthritis management. The acid/base hydrolysis of the unabsorbed diacerein in the colon is responsible for its laxative effect. Therefore, this work aimed to enhance the solubility, dissolution, and oral bioavailability of diacerein. Such enhancement means lower doses and fewer gastrointestinal adverse effects. A 4¹.3¹.2¹ full factorial design was adopted to prepare 24 solid dispersion formulae. Solid-state characterization showed the dissolution of diacerein crystals as metastable amorphous or microcrystalline forms in a matrix system that enhanced the drug dissolution. Desirability factor suggested compounding an optimized formula (F1) of Pluronic^®F68 with 1:3 drug:carrier ratio using rotavap that showed higher drug solubility (187.61 µg/mL) than drug powder (22.5 µg/mL). It achieved higher dissolution efficiency (4.04-fold) and rate (6.6-fold) as well as 100% release in 2 min. F1 was compressed into tablets recording greater dissolution efficiency (1.24-fold) and rate (12.5-fold) than the marketed product. The prepared tablet accomplished a 2.66-fold enhancement in diacerein bioavailability compared to the marketed product. In conclusion, the formulation of diacerein as solid dispersion loaded tablets could be of added value for the treatment of osteoarthritis in terms of enhanced patient compliance. Solid dispersion is an easy and scalable technique.

Keywords:

• Diacerein
• solid dispersion
• dissolution
• tablets
• osteoarthritis

Disclosure statement

No potential conflict of interest was reported by the author(s).