Thermo-kinetic mixing for pharmaceutical applications
Compositions and methods for making a pharmaceutical dosage form include making a pharmaceutical composition that includes one or more active pharmaceutical ingredients (API) with one or more pharmaceutically acceptable excipients by thermokinetic compounding into a composite. Compositions and methods of preprocessing a composite comprising one or more APIs with one or more excipients include thermokinetic compounding, comprising thermokinetic processing the APIs with the excipients into a composite, wherein the composite can be further processed by conventional methods known in the art, such as hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.
1. A method of making a pharmaceutical composition comprising the steps of:
providing a thermokinetic mixer;
combining one or more active pharmaceutical ingredients (APIs) with one or more pharmaceutically acceptable excipients in the thermokinetic mixer for thermokinetic compounding; and
mixing the one or more APIs with the one or more pharmaceutically acceptable excipients in the thermokinetic mixer for less than 300 seconds,
wherein the thermokinetic compounding of the one or more active pharmaceutical ingredients and the one or more pharmaceutically acceptable excipients forms a melt blended pharmaceutical composition wherein the one or more APIs comprise itraconazole and the one or more pharmaceutically acceptable excipients comprise hypromellose.
2. The method of claim 1 , wherein the thermokinetic compounding is thermokinetic mixing until melt blended.
3. The method of claim 1 , wherein the thermokinetic compounding is thermokinetic mixing prior to agglomeration.
4. The method of claim 1 , wherein the composite is a homogenous, heterogenous, or heterogeneously homogenous composite.
5. The method of claim 1 , wherein the thermokinetic processing includes a processing agent.
6. The method of claim 5 , wherein the processing agent is selected from the group consisting of a plasticizer, a thermal lubricant, an organic solvent, an agent that facilitates melt blending, and an agent that facilitates downstream processing.
7. The method of claim 1 , further comprising the step of adding a polymer carrier with a high melt viscosity.
8. The method of claim 1 , wherein the composition is formulated for immediate release, delayed release, or modified release.
9. The method of claim 1 , wherein the particle size of the one or more APIs is reduced to an average size of from 1000 μm to 1 μm.
10. The method of claim 1 , wherein the average particle size of the one or more APIs is less than 1 μm.
11. The method of claim 1 , wherein the one or more APIs comprises a small organic molecule, protein, peptide, or polynucleic acid.
12. The method of claim 1 , further comprising the step of processing the composite by hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.
13. The method of claim 1 , wherein the particle size of the one or more APIs is reduced to an average size of from 100 μm to 1 μm.
14. The method of claim 1 , wherein the particle size of the one or more APIs is reduced to an average size of from 10 μm to 1 μm.
15. A method of making a pharmaceutical composition comprising the steps of:
providing a thermokinetic mixer;
combining one or more active pharmaceutical ingredients (APIs) with one or more pharmaceutically acceptable excipients in the thermokinetic mixer for thermokinetic compounding; and
mixing the one or more APIs with the one or more pharmaceutically acceptable excipients in the thermokinetic mixer for less than 300 seconds,
wherein the thermokinetic compounding of the one or more active pharmaceutical ingredients and the one or more pharmaceutically acceptable excipients forms a melt blended pharmaceutical composition.
16. The method of claim 15 , wherein the one or more excipients are selected from the group consisting of lactose, glucose, starch, crystalline cellulose, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, methyl cellulose, dried starch, sodium alginate, powdered agar, calcium carmelose, a mixture of starch and lactose, sucrose, glycerin and starch, lactose, sucrose esters, cyclodextrins, cellulose derivatives and combinations thereof.
17. The method of claim 15 , wherein the one or more excipients are selected from the group consisting of calcium carbonate, kaoline, silicic acid, bentonite, colloidal silicic acid, talc, and combinations thereof.
18. The method of claim 15 , wherein the one or more excipients are selected from the group consisting of phosphatidyl choline derivatives, butter, hydrogenated oil, a mixture of a quarternary ammonium base and sodium lauryl sulfate, dipalmitoyl phosphadityl choline, deoxycholic acid and salts, sodium fusidate, stearates, sorbitan esters, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, oleic acid, lauric acid, vitamin E TPGS, and combinations thereof.
19. The method of claim 15 , wherein the one or more excipients is glycolic acid, salts of glycolic acid, or combinations thereof.
20. The method of claim 15 , wherein the one or more excipients are selected from the group consisting of a pharmaceutically acceptable polymer, a thermolabile polymeric excipient, and a non-polymeric excipient.
21. The method of claim 15 , wherein the one or more excipients are selected from the group consisting of starch, crystalline cellulose, starch solution, carboxymethyl cellulose, shellac, methyl cellulose, polyvinyl pyrrolidone, dried starch, calcium carmelose, polyethylene glycol, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, poloxamers (polyethylene-polypropylene glycol block copolymers), polyoxyethylated glycolysed glycerides, polyethylene glycols, polyglycolyzed glycerides, polyvinyl alcohols, polyacrylates, polymethacrylates, polyvinylpyrrolidones, cellulose derivatives, biocompatible polymers selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s and blends, combinations, and copolymers thereof.
22. The method of claim 15 , wherein the thermokinetic compounding is thermokinetic mixing until melt blended.
23. The method of claim 15 , wherein the thermokinetic compounding is thermokinetic mixing prior to agglomeration.
24. The method of claim 15 , wherein the composite is a homogenous, heterogenous, or heterogeneously homogenous composite.
25. The method of claim 15 , wherein the thermokinetic processing includes a processing agent.
26. The method of claim 25 , wherein the processing agent is selected from the group consisting of a plasticizer, a thermal lubricant, an organic solvent, an agent that facilitates melt blending, and an agent that facilitates downstream processing.
27. The method of claim 15 , further comprising the step of adding a polymer carrier with a high melt viscosity.
28. The method of claim 15 , wherein the composition is formulated for immediate release, delayed release, or modified release.
29. The method of claim 15 , wherein the particle size of the one or more APIs is reduced to an average size of from 1000 μm to 1 μm.
30. The method of claim 15 , wherein the particle size of the one or more APIs is reduced to an average size of from 100 μm to 1 μm.
31. The method of claim 15 , wherein the particle size of the one or more APIs is reduced to an average size of from 10 μm to 1 μm.
32. The method of claim 15 , wherein the average particle size of the one or more APIs is less than 1 μm.
33. The method of claim 15 , wherein the one or more APIs comprises a small organic molecule, protein, peptide, or polynucleic acid.
34. The method of claim 15 , further comprising the step of processing the composite by hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.
35. A method of making a pharmaceutical composition comprising the steps of:
providing a thermokinetic mixer;
combining one or more active pharmaceutical ingredients (APIs) with one or more pharmaceutically acceptable excipients in the thermokinetic mixer for thermokinetic compounding and
mixing the one or more active pharmaceutical ingredients with the one or more pharmaceutically acceptable excipients in the thermokinetic mixer,
wherein the thermokinetic compounding of the one or more active pharmaceutical ingredients and the one or more pharmaceutically acceptable excipients forms a melt blended pharmaceutical composition comprising one or more APIs having an average particle size of from 1000 μm to 1 μm.
36. The method of claim 35 , wherein the thermokinetic compounding is thermokinetic mixing until melt blended.
37. The method of claim 35 , wherein the thermokinetic compounding is thermokinetic mixing prior to agglomeration.
38. The method of claim 35 , wherein the composite is a homogenous, heterogenous, or heterogeneously homogenous composite.
39. The method of claim 35 , wherein the thermokinetic processing includes a processing agent.
40. The method of claim 39 , wherein the processing agent is selected from the group consisting of a plasticizer, a thermal lubricant, an organic solvent, an agent that facilitates melt blending, and an agent that facilitates downstream processing.
41. The method of claim 35 , further comprising the step of adding a polymer carrier with a high melt viscosity.
42. The method of claim 35 , wherein the composition is formulated for immediate release, delayed release, or modified release.
43. The method of claim 35 , wherein the one or more APIs comprises a small organic molecule, protein, peptide, or polynucleic acid.
44. The method of claim 31 , wherein the one or more excipients are selected from the group consisting of a pharmaceutically acceptable polymer, a thermolabile polymeric excipient, and a non-polymeric excipient.
45. The method of claim 35 , wherein the one or more excipients are selected from the group consisting of crystalline cellulose, starch solution, carboxymethyl cellulose, shellac, methyl cellulose, polyvinyl pyrrolidone, dried starch, calcium carmelose, polyethylene glycol, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, poloxamers (polyethylene-polypropylene glycol block copolymers), polyoxyethylated glycolysed glycerides, polyethylene glycols, polyglycolyzed glycerides, polyvinyl alcohols, polyacrylates, polymethacrylates, polyvinylpyrrolidones, cellulose derivatives, biocompatible polymers selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s and blends, combinations, and copolymers thereof.
46. The method of claim 35 , wherein the one or more excipients are selected from the group consisting of lactose, glucose, starch, crystalline cellulose, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, methyl cellulose, dried starch, sodium alginate, powdered agar, calcium carmelose, a mixture of starch and lactose, sucrose, glycerin and starch, lactose, sucrose esters, cyclodextrins, cellulose derivatives and combinations thereof.
47. The method of claim 35 , wherein the one or more excipients are selected from the group consisting of phosphatidyl choline derivatives, butter, hydrogenated oil, a mixture of a quarternary ammonium base and sodium lauryl sulfate, dipalmitoyl phosphadityl choline, deoxycholic acid and salts, sodium fusidate, stearates, sorbitan esters, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, oleic acid, lauric acid, vitamin E TPGS, and combinations thereof.
48. The method of claim 35 , wherein the one or more excipients are selected from the group consisting of calcium carbonate, kaoline, silicic acid, bentonite, colloidal silicic acid, talc, and combinations thereof.
49. The method of claim 35 , wherein the one or more excipients are glycolic acid, salts of glycolic acid, or combinations thereof.
50. The method of claim 35 , further comprising the step of processing the composite by hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.
51. The method of claim 35 , wherein the particle size of the one or more APIs is reduced to an average size of from 100 μm to 1 μm.
52. The method of claim 35 , wherein the particle size of the one or more APIs is reduced to an average size of from 10 μm to 1 μm.