PROGRAMMABLE ZERO-ORDER RELEASE TABLETS COMPRISING GEL-FORMING MATRIXAND WATER-INSOLUBLE DRUG EFFECT OF COMPOSITION AND FORMULATION PARAMETERS

A study was made of the effect of formulation parameters on the in vit ro release of sparingly water soluble drugs from matrix tablets contai ning a water soluble gel forming polymer: Mixtures of frusemide (chose n as the model drug) and a water soluble grade of polyvinyl alcohol we re granulated with alcoholic solution of low viscosity PVP K30 or high viscosity PVP K90. The formed granules were compressed into 0.5 g fla t faced tablets of different porosities. The tablets were then coated with an impermeable coating either on all surfaces except for one face or on the lateral surfaces leaving the two faces free. The effect of tablet composition and preparative conditions on release kinetics is d iscussed. The results show that the release rates of the drug from the constructed tablets were successfully sustained in comparison to thos e from commercial tablets containing the same amount of the drug. Alth ough the drug release from all tablets was zero-order, the release rat es were nonetheless found to decrease with an increasing drug/matrix r atio, the incorporation of high viscosity granulating PVP and by decre asing both tablet porosity and area of release. However, the effect of tablet thickness with the same porosity and drug/matrix ratio did not show any significant difference. The release rate could be adjusted o r altered without losing the zero-order release kinetics, by combining either the different compositions of the tablet matrix, the porosity or the surface area of release.