Effect of Gelucire® 44/14 on the Oral Bioavailability of Cyclosporin A
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Date
2007-06
Authors
Lim, Sin Yee
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Abstract
The present study was conducted to investigate the effect of Gelucire® 44/14 on
the oral bioavailability of a model lipophilic polypeptide drug, cyclosporin A.
Gelucire® 44/14 formulations of cyclosporin A at drug to Gelucire® 44114 ratios
of 1:4, 1:10, 1:14 and 1:20 (w/w) were successfully prepared using a heatfusion
method. In vitro studies showed that the aqueous solubility and
dissolution of cyclosporin A were proportionally increased with the amount of
Gelucire® used in the formulations. All formulations prepared could form stable
emulsion products when introduced into an aqueous medium. Moreover, upon
introduction into an aqueous medium, formulations with 1:10, 1:14 and 1:20
ratios of cyclosporin A to Gelucire® 44/14 formed emulsion products with
comparable droplet sizes to that using Gelucire® alone. Additionally,
incorporation of cyclosporin A into Gelucire® 44/14 did not alter the melting point
of the base.
A liquid chromatography tandem mass spectrometry method was successfully
developed for the determination of plasma concentrations of cyclosporin A. The
method was simple, sensitive, reproducible and specific and was applied to
evaluate the bioavailability of the 1 :10 formulation of cyclosporin A in Gelucire®
44/14.
The in vivo study conducted using Sprague-Dawley rats revealed that at a drug
to Gelucire® ratio of 1:10, the formulation was capable of increasing the oral
bioavailabiJity of cycJosporin A by approximately 2.8-fold compared to an
aqueous suspension of the drug and comparable to that of a commercially
available self-emulsifying formulation, Sandimmun Neoral®.
In conclusion, Gelucire® 44114 enhanced the solubility of a lipophilic polypeptide
drug, cyclosporin A, and subsequently increased the oral bioavailability of the
drug. Thus Gelucire® 44/14 could be a useful excipient in self-emulsifying
formulations for enhancing the oral bioavailability of lipophilic drugs.
Description
Keywords
Gelucire , Cyclosporin A