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. An anti-tussive modified release solid oral composition comprising (a) benzonatate in a matrix, wherein said matrix is a homogenous solid dispersion comprising (i) a benzonatate component, 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 benzonatate in a matrix (a), wherein there is no more than about 55% of the benzonatate released from the composition within 1 hour as determined in an in vitro dissolution test and substantially no benzonatate release from the composition in the buccal cavity.
2. The modified release solid oral benzonatate composition according to claim 1 , in which the matrix-forming substance is a hydrophilic polymer, wherein the composition 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 composition prior to coating.
3. The modified release solid oral benzonatate composition according to claim 2 , wherein the hydrophilic polymer is a low viscosity polymer.
4. The modified release solid oral benzonatate composition according to claim 3 , 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.
5. The modified release solid oral benzonatate 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.
6. The modified release solid oral benzonatate composition according to claim 5 , wherein said reverse enteric coating comprises a pH-dependent cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate.
7. The modified release solid oral benzonatate composition according to claim 5 , wherein said reverse enteric coating comprises about 5% to about 40% weight of said composition.
8. The modified release solid oral benzonatate composition according to claim 1 which is a compressed tablet.
9. The modified release solid oral benzonatate composition according to claim 8 , wherein the tablet further comprises at least one excipient selected from one or more of bulking agents, binders, and lubricants.
10. The modified release solid oral benzonatate composition according to claim 1 , wherein said solid oral composition comprises at least one or more additional pharmaceutically active components.
11. The modified release solid oral benzonatate composition according to claim 10 , 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.
12. The modified release solid oral benzonatate composition according to claim 10 , wherein said at least one or more additional active components are independently in immediate release form, in modified release form, or both.
13. The modified release solid oral benzonatate composition according claim 11 , wherein said at least one or more additional active components-is the expectorant guaifenesin.
14. The modified release solid oral benzonatate composition according to claim 11 , wherein at least one of the one or more additional active components is in the matrix.
15. A method for treating a patient with cough symptoms, said method comprising administering an effective oral dose of an anti-tussive modified release solid oral composition comprising (a) benzonatate in a matrix, wherein said matrix is a homogenous solid dispersion comprising (i) a benzonatate component, 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 benzonatate in a matrix (a), wherein there is no more than about 55% of the benzonatate released from the composition within 1 hour as determined in an in vitro dissolution test and substantially no benzonatate release from the composition in the buccal cavity.
16. The method according to claim 15 wherein the matrix-forming substance is a hydrophilic polymer, wherein the composition 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 composition prior to coating.
17. The method according to claim 15 , 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.
18. The method according to claim 17 , wherein said reverse enteric coating comprises a pH-dependent cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate.
19. The method according to claim 17 , wherein said reverse enteric coating comprises about 5% to about 40% weight of said composition.
20. The method according to claim 15 which is a compressed tablet.