Abstract

This study aimed to enhance Diacerein (DCN) solubility and bioavailability via proliposomes (PLS) prepared by the film deposition method. DCN/PLS were characterized for micromeritics, size, entrapment efficiency (EE), and in vitro study. The highest EE (91.13% ± 2.25%) and delayed DCN release (46.7%) at 12 hours were exhibited by positively charged liposomes (PLS-F16) containing one molar ratio of stearylamine with a particle size of 128.12 ± 17.90 nm. Fourier transform infra-red results revealed no drug-excipient interaction. Scanning electron microscopy, differential scanning calorimetry analysis, and powder X-ray diffractometry investigations confirm the amorphous phase of DCN in the prepared PLS. Stability studies showed that PLS was more stable than liposomes over a wide range of storage conditions variation. PLS formulations containing sorbitol (with ideal size, EE, and adequate in vitro release) were selected for fabrication of DCN controlled-release tablets by the direct compression technique using various concentrations of Eudragit RS100 and ethyl cellulose. PT-F10 (containing 225 mg EC) with minimum drug release (38.2%) at 12 hours showed significantly higher values of Cmax (7,455 ± 262.69 ng/ml), Tmax (8 ± 0.4 hours), and area under the plasma concentration curve–24 (913,013.7 ± 553.48 ng.hour/ml) when compared to marketed DCN capsules. The obtained results showed the potential of PLS as a carrier for DCN enhanced and prolonged oral bioavailability.

Key words: Diacerin, Osteoarthritis, Proliposomes, Enhanced bioavailability, Oral delivery, Pharmacokinetics