Benzonatate modified release solid tablets and capsules

摘要

A 12-hour anti-tussive modified release solid tablet or capsule is described which comprises a benzonatate in a matrix with a sufficient amount of one or more pharmaceutically acceptable modified release pH-independent, substances to provide a 12-hour modified release profile to the benzonatate, wherein there is substantially no benzonatate release from the tablet or capsule in the buccal cavity and no more than about 25% release of the benzonatate within 1 hour as determined in an in vitro dissolution assay. The modified release may be provided by (a) a high melt temperature, water-insoluble wax or waxy substance, (b) a low viscosity hydrophilic polymer such a hydroxypropyl methylcellulose, (c) a reverse enteric coating, or combinations thereof. The benzonatate may be in an adsorbate with a silico or silicate or in a complex with a weak acidic ion exchange resin complex.

主权项

1. A modified release solid oral composition comprising (a) a homogenous solid dispersion comprising (i) an adsorbate powder comprising benzonatate adsorbed onto an amorphous adsorbent selected from one or more of silica, silicon dioxide or silicate and (ii) at least one pharmaceutically acceptable modified release pH-independent, hydrophilic or hydrophobic matrix-forming substance in an amount effective to provide a modified release profile to the benzonatate, and (b) a reverse enteric coating over the homogenous solid dispersion of (a), wherein there is substantially no benzonatate release from the composition in the buccal cavity or esophagus following oral ingestion of the tablet, wherein said composition provides a pharmacokinetic profile for benzonatate in which the Cmax (arithmetic mean) is about 30 ng/mL, to about 35 ngmL and the AUCinf (arithmetic mean) is about 180 ng-h/mL to about 185 ng-h/mL, based on an equivalent of a single dose of about 300 mg benzonatate administered at 12 hour intervals in a 24 hour period.