oa SA Pharmaceutical Journal - Microemulsion drug delivery system : design and development for oral bioavailability enhancement of lovastatin : original research
Background: Lovastatin lowers cholesterol levels through reversible and competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), an enzyme involved in the biosynthesis of cholesterol. Oral bioavailability of lovastatin is < 5% because of rapid metabolism in the gut and liver. The main purpose of this research work was to develop a novel delivery system i.e. microemulsion (ME), and to study whether the oral bioavailability of lovastatin could be improved through this delivery system.
Method: A Capmul® MCM-based ME formulation with Cremophor® EL as surfactant, and Transcutol® P as co-surfactant, was developed for oral delivery of lovastatin. Pseudoternary phase diagram was constructed to determine the ME existing zone. Optimised ME was evaluated for its transparency, droplet size, zeta potential, viscosity, conductivity, percentage assay, and phase separation study. Solubilisation capacity of the ME system was also determined. An accelerated stability study of optimised ME was carried out to check the stability of the formulation. The prepared ME was compared with the pure drug solution and commercially available lovastatin tablet for in vitro drug release. Comparative oral absorption of lovastatin from the ME and suspension of the commercially available lovastatin was investigated through an in vivo study in a rat model.
Results: The optimised ME formulation containing lovastatin (20 mg), Capmul® MCM (7%), Cremophor® EL (24%), Transcutol®P (8%), and distilled water, had a droplet size (10 times diluted) and zeta potential (10 times diluted) of 27.9 nm and -3.11 mV respectively. The optimised ME was found to be stable for six months. ME showed higher in vitro drug release, as compared to plain drug suspension and the commercially available lovastatin. The in vivo studies revealed an increase of bioavailability (4.7 times) after oral administration of the ME formulation as compared with the commercially available lovastatin.
Conclusion: These results demonstrate the potential use of ME for improving the bioavailability of hydrophobic compounds, such as lovastatin by oral route.
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