Preparation and in vitro/vivo evaluation of a self-microemulsifying drug delivery system containing chrysin.

Abstract

OBJECTIVE\nTo prepare a self-microemulsifying drug delivery system (SMEDDS) to increase the solubility and oral bioavailability of chrysin.\n\n\nMETHODS\nThe preparation conditions were determined using factor analysis method. Preliminarily screening was conducted using compatibility tests and pseudo-ternary phase diagram studies. The Central Composite Design-Response Surface Methodology was used to determine the maximum drug loading and optimize SMEDDS formation, as characterized by surface morphology, pH, diameter, polydispersity index (PDI), zeta potential, and phase type. In vitro release of chrysin-suspension and chrysin-SMEDDS was investigated using the bulk-equilibrium reverse dialysis bag technique. Short-term stability of chrysin-SMEDDS at high and low temperatures was assessed. Pharmacokinetic behaviors were evaluated after intragastric and intravenous administration to rats.\n\n\nRESULTS\nThe final optimal formulation was medium chain triglyceride: oleic acid: Cremophor RH40: Transcutol HP (w/w) (12%: 12%: 32%: 44%), with a drug loading capacity of 5\u2009mg/g. Diluted chrysin-SMEDDS was characterized as an oil-in-water type and spherical, with a diameter, pH, PDI, and zeta potential of 28.26\u2009±\u20090.83\u2009nm, 5.60\u2009±\u20090.84, 0.18\u2009±\u20090.01, and -23.13\u2009±\u20090.95\u2009mV, respectively. The release speed of chrysin-SMEDDS was significantly higher than that of chrysin-suspension, and the release process was not affected by the media pH. In vivo pharmacokinetic data revealed that the oral bioavailability of chrysin-SMEDDS was 2.7-fold higher than that of chrysin suspension, compared with the chrysin microemulsion.\n\n\nCONCLUSIONS\nThe optimal SMEDDS formulation increased the dissolution and oral bioavailability of chrysin and may be useful for investigating chrysin efficacy in animal disease models and toxicokinetic studies.