BENZONATATE MODIFIED RELEASE SOLID TABLETS AND CAPSULES
A modified release benzonatate 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 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.
1 . A modified release solid oral composition comprising:
a matrix comprising (a) an adsorbate powder comprising benzonatate adsorbed to a silicon dioxide, and (b) at least one hydrophilic matrix forming material,
the composition provides benzonatate having a pharmacokinetic profile characterized by one or more of: an arithmetic mean Cmax of about 52 ng/mL, an arithmetic mean Cmax of about 60 ng/mL, a geometric mean AUCinf of about 137 ng.h/mL or an arithmetic mean AUCinf of about 160 ng.h/mL.
2 . The modified release solid oral composition according to claim 1 ,wherein the composition comprises mini-tabs loaded into a capsule.
3 . The modified release solid oral composition according to claim 1 , wherein the weight ratio of benzonatate to the amorphous adsorbent is in the range of about 5:1 to about 1:10.
4 . The modified release solid oral composition according to claim 1 , which comprises about 5% w/w to about 35% w/w, or about 5% w/w to about 30% w/w of the at least one hydrophilic polymer, based on the weight of the homogenous solid dispersion.
5 . The modified release solid oral composition according to claim 4 , wherein the matrix-forming substance comprises a low viscosity, hydrophilic polymer which is a hydroxypropyl methylcellulose having a viscosity of about 4000 mPa-s to about 100,000 mPa-s, or a blend of polymers containing said hydroxypropyl methycellulose.
6 . The modified release solid oral composition according to claim 1 , wherein said reverse enteric coating comprises (a) a pH-dependent methyl methacrylate and diethylaminoethyl methacrylate copolymer or (b) a pH-dependent cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate.
7 . The modified release solid oral composition according to claim 6 , wherein said reverse enteric coating comprises a pH-dependent cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate.
8 . The modified release solid oral composition according to claim 6 , wherein said reverse enteric coating comprises about 5% to about 40% weight of said composition.
9 . The modified release solid oral composition according to claim 6 which is a compressed tablet.
10 . The modified release solid oral composition according to claim 9 , wherein the tablet further comprises at least one excipient selected from one or more of bulking agents, binders, and lubricants.
11 . The modified release solid oral composition according to claim 1 , wherein said tablet further comprises at least one or more additional pharmaceutically active components.
12 . The modified release solid oral composition according to claim 1 , wherein said at least one or more additional active components is selected from an anti-pyretic, an analgesic, an anti-histamine, an expectorant and a decongestant.
13 . The modified release solid oral composition according to claim 12 , wherein said at least one or more additional active components are independently in immediate release form, in modified release form, or both.
14 . The modified release solid oral composition according claim 1 , wherein said at least one or more additional active components-is the expectorant guaifenesin.
15 . The modified release solid oral composition according to claim 14 , wherein at least one of the one or more additional active components is in the matrix.
16 . The modified release solid oral composition according to claim 1 , wherein the adsorbate powder of (a)(i) comprises particles having an average size of about 50 μm to about 200 μm.
17 . The modified release solid oral composition according to claim 1 , wherein the adsorbate powder of (a)(i) comprises at least about 55% w/w to about 60% w/w benzonatate.
18 . The modified release benzonatate solid composition according to claim 1 , wherein said reverse enteric coat comprises a butylated methacrylate copolymer.
19 . The modified release benzonatate solid composition according to claim 1 , wherein said solid dispersion further comprises one or more of microcrystalline cellulose, copovidone, hypromellose and magnesium stearate.
20 . A modified release solid oral composition comprising: (a) an adsorbate powder comprising benzonatate adsorbed to one or more of a silicon dioxide, and (b) a hydrophobic or hydrophilic matrix forming material, the composition provides benzonatate having a pharmacokinetic profile characterized by one or more of: a geometric mean maximum plasma concentration which has an area under the curve (AUC)inf of about 150 ng-h/mL and/or a Cmax of about 30 ng/mL.