Formulation and characterisation of self-microemulsifying drug delivery systems based on biocompatible nonionic surfactants

Abstract

Development of self-dispersing drug delivery systems (SMEDDS) is a modern strategy for oral delivery improvement of poorly soluble drugs. Self-microemulsifying drug delivery systems (SMEDDS) are isotropic mixtures of oils and hydrophilic surfactants, which form oil-in-water (o/w) microemulsions by dilution in aqueous media (e.g., gastrointestinal fluids). Formulation of SMEDDS carriers requires consideration of a large number of formulation parameters and their influences on process of self-microemulsifying and releasing of drug. The aim of this work was formulation and characterisation of SMEDDS for oral administration of ibuprofen. In the experimental work, two series of potential SMEDDS were prepared (M1-M10), using surfactant (Labrasol?, Gattefosse), cosurfactant (PEG-40 hydrogenated castor (Cremophor? RH40), and oil (medium chain triglycerides (Crodamol? GTCC) and olive oil (Cropur? Olive)), at surfactant-to-cosurfactant mass ratios (Km) 9:1, 7:3, 5:5, 3:7, and 1:9, and 10 % or 20 % of the oil phase. Ibuprofen was dissolved in formulations in concentration of 10 %. Characterisation of the investigated formulations included evaluation of physical stability, self-microemulsification ability in 0,1M HCl (pH 1.2) and phosphate buffer pH 7.2 (USP) and in vitro drug release. Formation of o/w microemulsions with the average droplet size (Z-ave) up to 100 nm, was observed in dispersions of formulations prepared with 10% w/w of medium chain triglycerides, within the entire investigated range of the Km values (M1-M5). These formulations were selected as SMEDDS. Results of characterisation pointed out the importance of the type and concentration of the oil as well as the Km value for the self-microemulsying ability as well as drug release kinetics from the investigated SMEDDS. Ibuprofen relase was in accordance with the request of USP 30-NF 25 (at least 80 %, after 60 min) from the formulations M1 (Km 9:1) and M5 (Km 1:9). Furthermore, ibuprofen release was completed after 10 minutes from formulation M1, while the release from the carrier M5 (~30 %) as well as from the commercial tablets Brufen? (~55%) and soft capsules Rapidol? (~65 %), examined under the same conditions, was significantly slower. The present study revealed that the formulation M1 represents a potential SMEDDS which efficiently solubilises ibuprofen in acidic media, with potential to minimise the side effects, while on introduction into alkaline intestinal environment, the drug may rapidly release from the carrier and undergo apsorption.