Benzonatate modified release solid tablets and capsules
AssigneeTris Pharma, Inc.
InventorsAndrea Nelson, Quin-Zene Chen, Harsh Mehta, Yu-Hsing Tu
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Abstract
A 12-hour anti-tussive modified release solid tablet or capsule is described which comprises a benzonatate adsorbate 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.
Claims41
A method for treating a patient with cough symptoms, said method comprising administering an effective oral dose of a modified release benzonatate solid oral composition comprising (a) a homogenous solid dispersion comprising (i) benzonatate adsorbed onto one or more of a silica, silicon dioxide or silicate to form a benzonatate adsorbate 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 coating over said homogenous solid dispersion,
- wherein there is substantially no benzonatate release from the composition in the buccal cavity, and
- wherein the composition provides a pharmacokinetic profile for benzonatate, based on an equivalent of about a 300 mg dose of benzonatate administered at 12 hour intervals in a 24 hour period, of one or more of:
- a geometric mean maximum plasma concentration which has an area under the curve (AUC)inf of about 110 ng-h/mL to about 170 ng-h/mL, a Cmax of about 15 ng/mL to about 25 ng/mL and/or a Tmax of about 12 hours to 20 hours.
A modified release solid oral composition comprising:
- a core and a reverse enteric coating over said core,
- wherein said core comprises benzonatate in a matrix, wherein said matrix is a homogenous solid dispersion comprising (a) an adsorbate powder comprising benzonatate and an amorphous adsorbent comprising a silicon dioxide, wherein the weight percentage of benzonatate in the adsorbate is about to 50% by weight benzonatate to about 75% by weight benzonatate, based on the weight of the adsorbate, (b) a pH-independent, hydrophilic matrix forming polymer, and wherein the ratio of the adsorbate powder to polymer is about 8:1 to about 1:1;
- and about 5% to about 20% by weight of a reverse enteric coating wherein the coating weight percentage is based on the total coated core prior to any optional seal coat, wherein there is substantially no benzonatate release from the composition in the buccal cavity or esophagus and no more than about 25% release of the benzonatate within 1 hour as determined in an in vitro dissolution assay.
Dependencies are inferred from the claim text.