Faculty of Pharmacy, Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, Egypt.
Faculty of Health and Life Sciences, Leicester Institute of Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester, UK.
Pharm Dev Technol. 2021 Mar;26(3):302-315. doi: 10.1080/10837450.2020.1869982. Epub 2021 Jan 11.
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 4.3.2 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 PluronicF68 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.
双醋瑞因是一种 BCS 类 II 药物，用于治疗骨关节炎。未被吸收的双醋瑞因在结肠中的酸碱水解负责其通便作用。因此，本工作旨在提高双醋瑞因的溶解度、溶解率和口服生物利用度。这种提高意味着更低的剂量和更少的胃肠道不良反应。采用 4.3.2 全因子设计制备了 24 种固体分散体配方。固态特征表明，双醋瑞因晶体在基质系统中溶解为亚稳定无定形或微晶形式，从而提高了药物的溶解率。理想性因子建议使用旋转蒸发器将泊洛沙姆 F68 与 1:3 的药物：载体比复配成优化配方（F1），其显示出比药物粉末（22.5μg/mL）更高的药物溶解度（187.61μg/mL）。它实现了更高的溶解效率（4.04 倍）和速率（6.6 倍），以及 2 分钟内 100%释放。F1 压制成片剂，其溶解效率（1.24 倍）和速率（12.5 倍）均优于市售产品。与市售产品相比，制备的片剂使双醋瑞因的生物利用度提高了 2.66 倍。总之，将双醋瑞因制成固体分散体负载片剂的配方可以提高患者的顺应性，从而为骨关节炎的治疗提供附加价值。固体分散体是一种简单且可扩展的技术。
