Eutectic formulations of cyclobenzaprine hydrochloride
The present invention relates to pharmaceutical compositions and methods of manufacturing the same, comprising a eutectic of Cyclobenzaprine HCl and mannitol.
1. A pharmaceutical composition comprising a eutectic of δ-mannitol and Cyclobenzaprine HCl, wherein the eutectic comprises 65%±2% Cyclobenzaprine HCl and 35%±2% δ-mannitol by weight.
2. The pharmaceutical composition of claim 1 , wherein the Cyclobenzaprine HCl is micronized Cyclobenzaprine HCl.
3. The pharmaceutical composition of claim 1 , further comprising a basifying agent.
4. The pharmaceutical composition of claim 3 , wherein the basifying agent is K 2 HPO 4 , Na 2 HPO 4 , or anhydrous trisodium citrate.
5. The pharmaceutical composition of claim 1 , wherein said composition comprises granules.
6. The pharmaceutical composition of claim 5 , wherein said granules comprise Cyclobenzaprine HCl and δ mannitol.
7. A method of manufacturing the pharmaceutical composition of claim 1 , comprising mixing Cyclobenzaprine HCl and mannitol in the presence of a solvent.
8. The method of claim 7 , wherein the mannitol is β mannitol or δ mannitol.
9. The method of claim 7 , wherein said mixing is wet granulation mixing.
10. The method of claim 7 , wherein the solvent is water, an alcohol or a mixture thereof.
11. The method of claim 10 , wherein said alcohol is methanol or ethanol.
12. The method of claim 9 , further comprising drying the mixture after said wet granulation.
13. The method of claim 12 , wherein said wet granulation and drying are repeated one or more times.
14. The method of claim 9 , further comprising crystallizing the Cyclobenzaprine HCl-mannitol mixture after said wet granulation.
15. The method of claim 14 , wherein said wet granulation and crystallization are repeated one or more times.
16. A method of manufacturing the pharmaceutical composition of claim 1 comprising fluid bed drying a mixture of Cyclobenzaprine HCl, mannitol, and a solvent.
17. The method of claim 16 , wherein the mannitol is β mannitol or δ mannitol.
18. The method of claim 16 , wherein the solvent is water, an alcohol or a mixture thereof.
19. The method of claim 18 , wherein the alcohol is methanol or ethanol.
20. The method of claim 16 , wherein the Cyclobenzaprine HCl is dissolved in the solvent and sprayed onto β mannitol particles inside a fluid bed dryer.
21. The pharmaceutical composition of claim 1 , wherein the δ-mannitol eutectic melts at 134° C.±3° C.
22. The method of claim 7 , wherein Cyclobenzaprine HCl is mixed with β mannitol.
23. The method of claim 22 , wherein the β mannitol converts to δ mannitol.