Abbott Laboratories Corporation

J Daniel Bollinger

Yihong Qiu

Howard S Cheskin

Sandeep Dutta

Kevin R Engh

Richard P Poska

Paul Richard Poska

Robert K Engh

A new oral polymeric controlled release formulation suitable for the once-a-day administration of valproate compounds, such as divalproex sodium, has been discovered. This formulation exhibits significant advantages over the sustained release valproate formulations of the prior art. This formulation minimizes the variation between peak and trough plasma levels of valproate over a 24 hour dosing period. This formulation follows a zero-order release pattern thus producing essentially flat plasma levels of valproate, once steady-state levels have been achieved. This results in a significantly lower incidence of side effects for patients consuming such a formulation.

Controlled release formulation of divalproex sodium

A controlled release tablet formulation which permits once daily dosing in the treatment of epilepsy comprises from about 50 weight percent to about 55 weight percent of an active ingredient selected from the group consisting of valproic acid, a pharmaceutically acceptable salt or ester of valproic acid, divalproex sodium, and valpromide; from about 20 weight percent to about 40 weight percent hydroxypropyl methylcellulose; from about 5 weight percent to about 15 weight percent lactose, from about 4 weight percent to about 6 weight percent microcrystalline cellulose, and from about 1 weight percent to about 5 weight percent silicon dioxide having an average particle size ranging between about 1 micron and about 10 microns; all weight percentages based upon the total weight of the tablet dosage form. Also disclosed are pre-tableting granular formulations, methods of making the granular formulations and tablets, and a method of treating epilepsy employing the controlled release tablet formulations of the invention.

The present invention pertains to a hydrophilic matrix tablet suitable for the once-a-day administration of valproate compounds such as divalproex sodium. The tablet comprises from about 50 weight percent to about 55 weight percent of an active ingredient selected from the group consisting of valproic acid, a pharmaceutically acceptable salt or ester of valproic acid, divalproex sodium, and valpromide; from about 20 weight percent to about 40 weight percent hydroxypropyl methylcellulose; from about 5 weight percent to about 15 weight percent lactose, from about 4 weight percent to about 6 weight percent microcrystalline cellulose, and from about 1 weight percent to about 5 weight percent of silicon dioxide; all weight percentages based upon the total weight of the tablet dosage form. Other aspects of the invention relate to the use of this formulation in the treatment of epilepsy and to methods for manufacturing this dosage form.

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Libertyville, IL, United States of America

J Daniel Bollinger