Development of novel solid dispersion of tranilast using amphiphilic block copolymer for improved oral bioavailability

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The present study aimed to develop novel solid dispersion (SD) of tranilast (TL) using amphiphilic block copolymer, poly[MPC-co-BMA] (pMB), to improve the dissolution and pharmacokinetic behavior of TL. pMB-based SD of TL (pMB-SD/TL) with drug loading of 50% (w/w) was prepared by wet-mill technology, and the physicochemical properties were characterized in terms of morphology, crystallinity, dissolution, and hygroscopicity. Powder X-ray diffraction and polarized light microscopic experiments demonstrated high crystallinity of TL in pMB-SD/TL. The pMB-SD/TL exhibited immediate micellization when introduced to aqueous media, forming fine droplets with a mean diameter of ca. 122 nm. There was marked improvement in the dissolution behavior for the pMB-SD/TL even under acidic conditions, although the supersaturated TL concentration gradually decreased. NMR analyses demonstrated interaction between TL and pMB, as evidenced by the chemical shift drifting and line broadening. Pharmacokinetic behaviors of orally dosed TL formulations were evaluated in rats using UPLC/ESI-MS. After oral administration of pMB-SD/TL (10 mg TL/kg) in rats, enhanced TL exposure was observed with increases of Cmax and AUC by 125- and 52-fold, respectively, compared with those of crystalline TL. From these findings, pMB-based SD formulation approach might be an efficacious approach for enhancing the therapeutic potential of TL.

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