Self-emulsifying active substance formulation and use of this formulation
View Patent ↗The present invention relates to self-emulsifying formulations based on an active ingredient component and a formulation base with a lipid component and with a binder component and to the use of this formulation as dosage form in the life science sector. The invention also describes a process for producing self-emulsifying formulations by mixing the formulation components to form a plastic mixture and, where appropriate, to manufacture the formulations as dosage form advantageously by use of melt extrusion. The formulations spontaneously form emulsions in water or aqueous media.
1. A self-emulsifying formulation comprising
i) 0.1 to 50% by weight of an active ingredient component comprising at least one active ingredient, and having a content of active ingredient crystals of less than 5%;
ii) 6 to 60% by weight of a lipid component comprising at least one lipid, and having a melting point not exceeding 50° C., wherein the lipid component has an HLB not exceeding 12;
iii) 20 to 93.9% by weight of a binder component comprising a binder selected from polyvinylpyrrolidones, vinylpyrrolidone/vinylacetate copolymers, hydroxyalkylcelluloses, hydroxyalkylalkylcelluloses, cellulose phthalates and (meth)acrylic resins; and
iv) 0 to 30% by weight of at least one further excipient, wherein the content of lipid component based on the binder component does not exceed 40% by weight.
2. The formulation of claim 1 , wherein the formulation is essentially free of active ingredient crystals.
3. The formulation of claim 1 , wherein the active ingredient has a low solubility in water.
4. The formulation of claim 1 , wherein the lipid is selected from fatty acids, triglycerides, diglycerides or monoglycerides.
5. The formulation of claim 1 , wherein the lipid is selected from unsaturated fatty acids, mono-, di- or triglycerides of unsaturated fatty acids.
6. The formulation of claim 5 , wherein the unsaturated fatty acid is selected from oleic acid, linolic acid or linolenic acid.
7. The formulation of claim 1 , wherein the lipid component has a melting point of less than 30° C.
8. The formulation of claim 1 , wherein the lipid component is in the form of a molecular dispersion.
9. The formulation of claim 1 , wherein the content of lipid component based on the binder component does not exceed 25% by weight.
10. The formulation of claim 1 , wherein the binder is selected from polyvinylpyrrolidones, vinylpyrrolidone copolymers with vinyl acetate, hydroxypropylcelluloses or hydroxypropylmethylcelluloses.
11. The formulation of claim 1 , wherein the further excipient is selected from fillers, lubricants, glidants, mold release agents, flow regulators, dyes, stabilizers, plasticizers, wetting agents, preservatives, disintegrants, adsorbents or surfactants.
12. The formulation of claim 1 , wherein the formulation is obtainable by melt extrusion of a plastic mixture comprising the components i), ii), iii) and optionally iv).
13. The formulation of claim 1 , wherein the formulation is solid.
14. The formulation of claim 1 , wherein at least part of the active ingredient component is in the form of a molecular dispersion, and wherein the binder is selected from polyvinylpyrrolidones, vinylpyrrolidone copolymers with vinyl acetate, hydroxypropylcelluloses or hydroxypropylmethylcelluloses.
15. The formulation of claim 14 , wherein said molecular dispersion is a solid solution, and the formulation is essentially free of active ingredient crystals.
16. The formulation of claim 15 , wherein said formulation is essentially free of lipid crystals.
17. The formulation of claim 15 , wherein the formulation active ingredient is an active pharmaceutical ingredient.
18. The formulation of claim 17 , wherein said lipid is a mono-, di- or triglyceride.
19. The formulation of claim 1 , wherein the formulation comprises 1 to 30% by weight of the active ingredient component.
20. The formulation of claim 14 , wherein the formulation comprises 1 to 30% by weight of the active ingredient component.
21. The formulation of claim 17 , wherein the formulation comprises 1 to 30% by weight of the active ingredient component.
22. The formulation of claim 1 , wherein the formulation comprises 5 to 20% by weight of the active ingredient component.
23. The formulation of claim 14 , wherein the formulation comprises 5 to 20% by weight of the active ingredient component.
24. The formulation of claim 17 , wherein the formulation comprises 5 to 20% by weight of the active ingredient component.
25. The formulation of claim 1 , wherein the formulation comprises 30 to 90% by weight of the binder component.
26. The formulation of claim 14 , wherein the formulation comprises 30 to 90% by weight of the binder component.
27. The formulation of claim 17 , wherein the formulation comprises 30 to 90% by weight of the binder component.
28. The formulation of claim 19 , wherein the formulation comprises 30 to 90% by weight of the binder component.
29. The formulation of claim 20 , wherein the formulation comprises 30 to 90% by weight of the binder component.
30. The formulation of claim 21 , wherein the formulation comprises 30 to 90% by weight of the binder component.
31. The formulation of claim 22 , wherein the formulation comprises 30 to 90% by weight of the binder component.
32. The formulation of claim 23 , wherein the formulation comprises 30 to 90% by weight of the binder component.
33. The formulation of claim 24 , wherein the formulation comprises 30 to 90% by weight of the binder component.
34. The formulation of claim 18 , wherein at least part of the lipid component and at least part of the binder component form a molecular dispersion.
35. The formulation of claim 31 , wherein said formulation is essentially free of lipid crystals.
36. The formulation of claim 1 , wherein the formulation is in the form of a molecular dispersion and is essentially free of lipid and active ingredient crystals.
37. The formulation of claim 36 , wherein the formulation comprises a molecular dispersion of the lipid component in the binder component.
38. The formulation of claim 36 , wherein the formulation is essentially amorphous.
39. The formulation of claim 38 , wherein the lipid component has an HLB not exceeding 8.
40. The formulation of claim 38 , wherein the lipid component has an HLB not exceeding 5.
41. The formulation of claim 38 , wherein the binder component is a vinylpyrrolidone/vinyl acetate copolymer having a vinylpyrrolidone: vinyl acetate ratio of 60:40.
42. The formulation of claim 38 , wherein the binder component comprises a sugar alcohol.
43. The formulation of claim 38 , wherein the formulation comprises 40 to 80% by weight of the binder component.
44. The formulation of claim 38 , wherein the binder component is selected from polyvinylpyrrolidone, vinylpyrrolidone copolymers with vinyl acetate, hydroxypropylcelluloses, hydroxypropylmethylcelluloses, or hydroxypropylmethylcellulose phthalate.
45. The formulation of claim 44 , wherein the formulation comprises 40 to 80% by weight of the binder component.
46. The formulation of claim 38 , wherein the active ingredient has a low solubility in water.
47. The formulation of claim 46 , wherein the formulation comprises a molecular dispersion of the lipid component in the binder component.
48. The formulation of claim 46 , wherein the content of lipid component based on the binder component does not exceed 25% by weight.