Utility of a novel self-emulsifying system for a lipophilic drug with low oral bioavailability

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Date
2006
Authors
Wai Peng, Choy
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Abstract
The present study was conducted to formulate a self-emulsifying system (SES) for enhancing the systemic absorption of poorly bioavailable lipophilic drugs, using ubiquinone as the model drug. A simple high performance liquid chromatographic method with the required specificity, precision and accuracy was first developed for quantification of ubiquinone in rat and human plasma. Several aspects leading to the formulation of a suitable SES for ubiquinone were first studied. They included the determination of the ubiquinone lipid solubility (log P octanoltaqueous), evaluation of various potential oily vehicles, type and concentrations of surfactants, the self-emulsification efficiency and emulsion droplet sizes of various surfactant and vehicle combinations and finally the drug loading and chemical stability of ubiquinone in the self-emulsifying (SE) formulations. From these studies, an optimised SE formulation comprising a 9:1 w/w mixture of a-linolenic acid and Cremophor® EL loaded with 60 mg/g of ubiquinone was found to have the most satisfactory in vitro performance. An in vivo study conducted using Sprague-Dawley rats revealed that the oral bioavailability of the optimised SE formulation was comparable to that of a commercially available self-microemulsifying (SME) ubiquinone formulation, Q-Gel® Forte. Another in vivo study was also carried out using healthy human volunteers, comparing the optimised SE formulation to Q-Gel® Forte as well as another commercially available oily suspension of ubiquinone, Bio-Quinone. It was found that the extent of bioavailability of the optimised SE formulation was slightly higher (although not statistically significant) than that of Q-Gel® Forte and both were significantly (p<0.05) higher than the oily drug suspension, Bio-Quinone. In conclusion, the optimised SE formulation comprising a 9:1 w/w mixture of a-linolenic acid and Cremophor® EL could self-emulsify satisfactorily and also enhance the oral bioavailability of lipophilic drugs such as ubiquinone.
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Self-emulsifing system , Oral bioavailability
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