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 method of manufacturing a pharmaceutical composition comprising a eutectic of Amitriptyline HCl and mannitol, wherein the pharmaceutical composition comprises amounts of Amitriptyline HCl and mannitol selected from: 40%+2% Amitriptyline HCl and 60%±2% mannitol, 45%±2% Amitriptyline HCl and 55%±2% mannitol, 50%±2% Amitriptyline HCl and 50%±2% mannitol, 55%±2% Amitriptyline HCl and 45%±2% mannitol, 60%±2% Amitriptyline HCl and 40%±2% mannitol, 65%±2% Amitriptyline HCl and 35%±2% mannitol, 70%±2% Amitriptyline HCl and 30%±2% mannitol, 80%±2% Amitriptyline HCl and 20%±2% mannitol, 85%±2% Amitriptyline HCl and 15%±2% mannitol, and 90%±2% Amitriptyline HCl and 10%±2% mannitol by weight, the method comprising mixing Amitriptyline HCl and mannitol or milling Amitriptyline HCl and mannitol.
2. The method of claim 1 , comprising milling Amitriptyline HCl and mannitol.
3. The method of claim 2 , wherein, the Amitriptyline HCl and mannitol are milled in a high shear granulator.
4. The method of claim 1 , comprising mixing Amitriptyline HCl and mannitol.
5. The method of claim 4 , wherein the Amitriptyline HCl and mannitol are mixed via compression.
6. The method of claim 5 , wherein the Amitriptyline HCl and mannitol are compressed via roller compaction.
7. A method of manufacturing a pharmaceutical composition comprising a eutectic of Amitriptyline HCl and mannitol, wherein the pharmaceutical composition comprises amounts of Amitriptyline HCl and mannitol selected from: 40%±2% Amitriptyline HCl and 60%±2% mannitol, 45%±2% Amitriptyline HCl and 55%±2% mannitol, 50%±2% Amitriptyline HCl and 50%±2% mannitol, 55%±2% Amitriptyline HCl and 45%±2% mannitol, 60%±2% Amitriptyline HCl and 40%±2% mannitol, 65%±2% Amitriptyline HCl and 35%-2% mannitol, 70%±2% Amitriptyline HCl and 30%±2% mannitol, 75%±2% Amitriptyline HCl and 25%±2% mannitol, 80%±2% Amitriptyline HCl and 20%±2% mannitol, 85%±2% Amitriptyline HCl and 15%±2% mannitol, and 90%±2% Amitriptyline HCl and 10%±2% mannitol by weight, the method comprising spray drying Amitriptyline HCl and mannitol.
8. The method of claim 1 or 7 , wherein the Amitriptyline HCl is micronized Amitriptyline HCl.
9. The method of claim 1 or 7 , wherein the pharmaceutical composition comprises a basifying agent.
10. The method of claim 9 , wherein the basifying agent is K 2 HPO 4 , Na 2 HPO 4 or anhydrous trisodium citrate.
11. The method of claim 1 or 7 , wherein the eutectic composition comprises β mannitol.
12. The method of claim 1 or 7 , wherein the eutectic composition comprises δ mannitol.