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