Development and Optimization of Selfmicroemulsifying Drug Delivery of Domperidone

Abstract

Purpose: Majority of drugs invented in laboratory are not marketed successfully due to poor aqueous solubility. Amongst all, formulation of solid self micro emulsifying drug delivery system is one of the better options to improve bioavailability of such hydrophobic drugs. It was aimed in present investigation to develop self micro emulsifying drug delivery system (SMEDDS) to improve the dissolution and hence bioavailability of a BCS class II anti emetic agent, domperidone. Methods: Self micro emulsifying formulation consists of oil, surfactant and cosurfactant in addition to drug. Solubility study was performed in selected components individually to identify the ingredients showing highest solubility of domperidone. The ternary phase diagram was plotted for selected components to identify the area of microemulsion existence. D-optimal mixture experimental design was applied to optimize a liquid SMEDDS using formulation variables; the oil phase X1 (Oleic acid), the surfactant X2 (Labrasol) and the co-surfactant X3 (Transcutol HP). The liquid SMEDDS were evaluated for droplet size, emulsification time, % transmittance and drug release. Stability study was performed at 40°C/75% RH. Liquid formulation was solidified by adsorption on carrier aerosil. Solid SMEDDS was evaluated and compared with liquid SMEDDS. Optimised formulation was evaluated using X-Ray powder diffraction. Results: Based on higher solubility, oleic acid was selected as oil, Labrasol as surfactant and Transcutol HP as cosurfactant for formulation of SMEDDS. Out of 16 batches formulated as per D optimal design, the batch containing 10% oil and 45% surfactant and 45% cosurfactant showed best results in term of smaller droplet size (< 170 nm), emulsification time (< 40 sec) with good percent transmittance (> 90 %) and drug release (> 85% in 15 min) and was stable for 3 months. Solid SMEDDS containing aerosil 300 (30% w/w of liquid SMEDDS) showed good flow properties and uniform drug content. XRPD study revealed that the crystalline drug was converted to amorphous form in solid SMEDDS. The rate and extent of drug dissolution for solid SMEDDS was significantly higher than pure drug and commercial tablet formulation. Conclusion: The result demonstrate the potential use of SMEDDS as a means of improving solubility, dissolution and hence the bioavailability.