Cefpodoxime-proxetil protection from intestinal lumen hydrolysis by oil-in-water submicron emulsions

Cefpodoxime proxetil is an orally active, broad spectrum, third generation cephalosporin ester, This prodrug was previously found to be hydrolyzed in vitro both in rabbit and human duodenal washing by a cholinesterase. The objective of this work was to find a formulation which can protect the prodrug: from enzymatic attack. In order to protect the prodrug from enzymatic hydrolysis, the objective was to include it into the oil phase of an oil-in-water (o/w) emulsion. Somehow, cefpodoxime proxetil posed specific problems related to the solubilization. The solubilization was obtained with a mixed medium-chain-triglycerides (MCT)/blends of mono-, di-and triglycerides oil phase and the optimal ratio was defined to be 60:40 (w/w) in order to obtain emulsification. The emulsifier was a soybean lecithin alone or in mixtures with polysorbate 20. This non-ionic surfactant was chosen since it was found to directly inhibit the hydrolysis of cefpodoxime proxetil in vitro using duodenal washings. The o/w submicron emulsions were proven to be effective in protecting the prodrug from enzymatic attack in rabbit duodenal washings compared with a micellar solution and an aqueous solution of cefpodoxime proxetil. An o/w submicron emulsion incorporating polysorbate 20 was found to be the most protective, which can corroborate the inhibitory role of polysorbate itself. (C) 1998 Elsevier Science B.V. All rights reserved.