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 characterization 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 (PEG­40 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%. Characterization of the investigated formulations included evaluation of physical stability, self-microemulsification ability in 0.1 M 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 mass% of medium chain triglycerides, within the entire investigated range of the Km values (M1-M5). These formulations were selected as SMEDDS. Results of characterization pointed out the importance of the type and concentration of the oil as well as the Km value for the self-microemulsing ability, as well as drug release kinetics from the investigated SMEDDS. Ibuprofen release 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, the ibuprofen release was completed after 10 min 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 dissolves ibuprofen in acidic media, with potential to minimize the side effects, while on introduction into alkaline intestinal environment, the drug may rapidly release from the carrier and undergo absorption.

Razvoj samo-mikroemulgujućih nosača je značajna savremena strategija za unapređenje peroralne primene teško rastvorljivih aktivnih supstanci. Cilj rada bio je formulacija i karakterizacija samo-mikroemulgujućih nosača na bazi smeše biokompatibilnih nejonskih surfaktanata (PEG-8 kaprilno/kaprinski gliceridi (Labrasol®) i PEG-40 hidrogenizovano ricinusovo ulje (Cremophor® RH40)) za peroralnu primenu ibuprofena i in vitro karakterizacija njihove fizičke stabilnosti i veličine kapi nakon dispergovanja u vodenim medijumima različite pH vrednosti i in vitro profila oslobađanja lekovite supstance iz nosača. Rezultati karakterizacije ukazali su na značaj vrste i koncentracije ulja i masenog odnosa upotrebljenih surfaktanata za sposobnost samo-mikroemulgovanja, kapacitet za solubilizaciju ibuprofena i njegovu brzinu oslobađanja iz nosača.