Exploring the potential of self-assembled mixed micelles in enhancing the stability and oral bioavailability of an acid-labile drug

Abstract

Oral delivery of many drugs is plagued with limited solubility and/or poor stability. This paper aimed to explore the performance of polymeric mixed micelles on solubilization, stabilization and bioavailability enhancement with stiripentol as model drug. Stiripentol-loaded mixed micelles were prepared by solvent-diffusion method: rapid dispersion of an ethanol solution containing stiripentol, monomethoxy poly(ethylene glycol)-b-poly(ε-caprolactone) and sodium oleate into water. Stiripentol micelles were characterized by the particle size, entrapment efficiency, in vitro drug release, TEM, DSC and FTIR. The pharmacokinetic profile of stiripentol was determined in rats after oral administration of stiripentol micelles. The obtained stiripentol micelles were 44.2 nm in size with an entrapment efficiency over 90%. It was shown that micelles substantially improved the solubility and gastric stability of stiripentol. The oral absorption of stiripentol was also enhanced to a great extent with a relative bioavailability of 157% and 444% to the commercial formulation (Diacomit®) and in-house suspensions. Mixed micelles assembled by di-block copolymer/sodium oleate exhibited a good potential in the improvement of drug stability and bioavailability. It should be a promising carrier for oral delivery of therapeuticals with solubility and stability issues.

Keywords: Absorption potential; Bioavailability; Caprolactone (PubChem CID: 10401); Carboxymethylcellulose sodium (PubChem CID: 23706213); Dichloromethane (PubChem CID: 6344); Diethyl ether (PubChem CID: 3283); Methoxypolyethylene glycol (PubChem CID: 24887753); Micelles; Phosphotungstic acid hydrate (PubChem CID: 16212977); SNX-2112 (PubChem CID: 24772860); Sodium oleate (PubChem CID: 23665730); Solubility; Stability; Stannous octoate (PubChem CID: 9318); Stiripentol; Stiripentol (PubChem CID: 5311454).