Ashok C. Shah

Gel-matrixsystems exhibiting bimodal controlled release for oral drug delivery

Abstract Certain types of hydroxypropyl methylcellulose ethers, when admixed with a therapeutic agent and compressed into a solid dosage form, are found to display a bimodal drug release profile. The bimodal profile is characterized by a rapid initial release of drug, followed by a constant rate of release, and then a second mode of fast drug release at the terminal phase. Release profiles can be selectively modified by varying the viscosity, concentration, and the combination of methylcellulose polymers. The mechanism of release appears to involve initial surface erosion, polymer gelation, a steady-state counter-current permeation of water and dissolved drug across the gel layer, dissolution of gel from the outer surface, and subsequent disintegration of the gel. A bimodal oral controlled release delivery system which produces an increased rate of drug release in the latter phases of dissolution, may offer some advantages over constant zero-order release systems for maintaining uniform drug levels in the body. Bimodal release profiles were obtained for aspirin, ibuprofen, adinazolam, flurbiprofen, and other investigational drugs.

Novel divisible tablet designs for sustained release formulations

Novel divisible tablet designs have been developed, which minimize the formation of new surface area upon division and thereby provide a means of administering a portion of the sustained release dose without appreciably altering the rate of drug release. A U.S. patent has been issued, claiming these divisible tablets for fractional dosing of sustained release medications [1]. Basic design features include lateral grooves on the top and bottom tablet surfaces at each line of division, which may be of variable depth, and a tablet shape that produces deep transverse grooves on the side of the tablet. Tablet shape, as well as the depth and angle of the dividing grooves, may be varied depending on the number of divisions desired, tablet size, weight, mechanical strength, and other formulation considerations. Distinctive features of oval bi-dosage tablets, oval tri-dos-age tablets, and elliptical bi-dosage tablets are examined. Divisible oval bi-dosage sustained released 400 mg Motrin tablets were evaluated. Cleavage resulted in tablet segments containing half the dosage of the whole tablet (within <0.2%). An increase in surface area, upon division, of only 2.49% was observed. In vitro drug release rates for the Motrin half tablets were essentially equivalent to those of the whole tablets.