DEVELOPMENT OF AN ORAL SUSTAINED-RELEASE ANTIBIOTIC MATRIX TABLET USING IN-VITRO IN-VIVO CORRELATIONS

A sustained release (SR) cephalexin tablet formulation containing xant han gum and sodium alginate as matrix formers was evaluated in human v olunteers. The formulation was optimized based on response surface ana lysis and computer simulation of cephalexin plasma levels versus time curves. The optimized formulation was tested in-vivo in human voluntee rs along with a fast release (FR) capsule formulation. The SR matrix f ormulation prolonged the cephalexin blood levels up to 8 hours in huma ns. The matrix formulation reduced variations in cephalexin plasma lev els in individual subjects without any dose dumping as compared to the FR formulation. The plasma levels predicted by the computer program u sing in-vitro release data and the drug's pharmacokinetic parameters s howed excellent correlation with in-vivo data. Using the Wagner-Nelson method, there was good correlation between in-vitro dissolution and i n-vivo absorption in individual subjects. The relative bioavailability of cephalexin was reduced by about thirty percent. Very little absorp tion was seen after six to eight hours. The SR matrix formulation is a n alternative delivery method to produce prolonged concentrations.