IN VITRO AND IN VIVO STUDIES OF THE EFFECT OF PROTEINS ON THE DISSOLUTION AND ABSORPTION OF DICUMAROL, NITROFURANTOIN AND SULFAMETHIZOLE
Abstract
IN THIS PHD THESIS THE MECHANISMS WITH WHICH SMALL QUANTITIES OF PROTEINS CAN ALTER THE BIOAVAILABILITY OF POORLY WATER SOLUBLE DRUGS (AT CONCENTRATIONS SIMILAR TO THOSE THEY ARE MET IN FOODSTUFFS) WERE INVESTIGATED. NITROFURANTOIN, DICUMAROL AND SULFAMETHIZOLE WERE CHOSEN AS MODEL DRUGS. BOVINE SERUM ALBUMIN AND CASEIN WERE USED AS MODEL PROTEINS. THE IN VITRO STUDIES INCLUDED DISSOLUTION AND TRANSPORT OF ALL DRUGS THOUGH DIALYSIS MEMBRANES. MOREOVER PROTEIN BINDING, SOLUBILITY, VISCOSITY AND SURFACE TENSION MEASUREMENTS WERE MADE AS WELLAS PARTICLE SIZE ANALYSIS OF THE POWDERS. THE EFFECT OF LOW FAT MILK ON THE BIOAVAILABILITY WAS ALSO STUDIED. FINALLY, A NEW DOSAGE FORM WAS SUGGESTED: THEFREEZE DRIED (LYOPHILIZED) DRUG-MILK FORMULATIONS SHOWED FASTER AND MORE CONSISTENT ABSORPTION THAN OTHER TYPICAL DOSAGE FORMS AND ARE PROMISING AS A NEW DRUG DELIVERY SYSTEM.
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