Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
The present invention relates to pharmaceutical compositions and methods of manufacturing the same, comprising a eutectic of Cyclobenzaprine HCl and mannitol or Amitriptyline HCl and mannitol.
1. A pharmaceutical composition comprising a eutectic of 25%±2% mannitol and 75%±2% Cyclobenzaprine HCl by weight, wherein the mannitol is β-mannitol or δ-mannitol.
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 .
5. The pharmaceutical composition of claim 3 , wherein the basifying agent is Na 2 HPO 4 .
6. The pharmaceutical composition of claim 3 , wherein the basifying agent is anhydrous trisodium citrate.
7. A method of manufacturing a pharmaceutical composition of claim 1 , comprising mixing the Cyclobenzaprine HCl and the mannitol or milling the Cyclobenzaprine HCl and the mannitol.
8. The method of claim 7 , comprising milling the Cyclobenzaprine HCl and the mannitol.
9. The method of claim 8 , wherein, the Cyclobenzaprine HCl and the mannitol are milled in a high shear granulator.
10. The method of claim 7 , comprising mixing the Cyclobenzaprine HCl and the mannitol.
11. The method of claim 10 , wherein the Cyclobenzaprine HCl and the mannitol are mixed via compression.
12. The method of claim 11 , wherein the Cyclobenzaprine HCl and the mannitol are compressed via roller compaction.
13. A method of manufacturing a pharmaceutical composition of claim 1 , comprising spray drying a mixture of the Cyclobenzaprine HCl and the mannitol.
14. The method of claim 7 , wherein the Cyclobenzaprine HCl is micronized Cyclobenzaprine HCl.
15. The method of claim 7 , wherein the pharmaceutical composition further comprises a basifying agent.
16. The method of claim 15 , wherein the basifying agent is K 2 HPO 4 .
17. The method of claim 15 , wherein the basifying agent is Na 2 HPO 4 .
18. The method of claim 15 , wherein the basifying agent is anhydrous trisodium citrate.
19. The pharmaceutical composition of claim 1 , wherein the mannitol in the eutectic is β mannitol.
20. The pharmaceutical composition of claim 19 , wherein the eutectic melts at 143.6±3° C.
21. The pharmaceutical composition of claim 1 , wherein the mannitol in the eutectic is δ mannitol.
22. The pharmaceutical composition of claim 21 , wherein the eutectic melts at 134° C±3° C.
23. The method of claim 7 , wherein the mannitol in the eutectic is β mannitol.
24. The method of claim 23 , wherein the eutectic melts at 143.6±3° C.
25. The method of claim 7 , wherein the mannitol in the eutectic is δ mannitol.
26. The method of claim 25 , wherein the eutectic melts at 134° C±3° C.
27. The method of claim 13 , wherein the pharmaceutical composition further comprises a basifying agent.
28. The method of claim 27 , wherein the basifying agent is K 2 HPO 4 .
29. The method of claim 27 , wherein the basifying agent is Na 2 HPO 4 .
30. The method of claim 27 , wherein the basifying agent is anhydrous trisodium citrate.
31. The method of claim 13 , wherein the mannitol in the eutectic is δ mannitol.
32. The method of claim 31 , wherein the eutectic melts at 134° C±3° C.
33. The method of claim 13 , wherein the mannitol is β-mannitol.
34. The method of claim 13 , wherein the spray drying converts the β-mannitol into δ-mannitol.