Injectable pharmaceutical composition for systematic administration of pharmacologically active ingredients
View Patent ↗The invention relates to novel pharmaceutical compositions for the systemic administration of pharmacologically active ingredients. The invention relates in particular to an injectable pharmaceutical composition comprising (a) a pharmacologically active ingredient in a solid phase, (b) a vehicle consisting substantially of polyol fatty acid esters with a degree of esterification of over 80%, and (c) a wetting agent consisting substantially of polyol fatty acid esters with a monoester proportion of over 60%. The inventive composition is used for the systemic administration of numerous pharmacologically active ingredients, whereby the ingredients are released from the pharmaceutical composition over a period of at least 12, preferably at least 24 hours.
1. An injectable pharmaceutical composition comprising:
(a) at least one pharmacologically active agent in its solid phase;
(b) a vehicle essentially consisting of polyol fatty acid esters with an esterification level of over 80%; and
(c) a wetting agent comprising polyol fatty acid esters with a monoester content of over 60%,
wherein the active agent is an antiparkinsonian agent which is released in the body from the injectable pharmaceutical composition in a therapeutically effective amount over a time period of at least 24 hours.
2. The injectable pharmaceutical composition of claim 1 , wherein the vehicle is more than 70% (w/w) of the total composition.
3. The pharmaceutical composition of claim 1 or 2 wherein the pharmaceutical composition is anhydrous.
4. The pharmaceutical composition of claim 1 or 2 wherein the pharmacologically active agent is substantially insoluble in the pharmaceutical composition.
5. The pharmaceutical composition of claim 1 or 2 wherein the vehicle consists essentially of polyol fatty acid esters containing as the polyol component 1,3-propanediol, 1,3-butanediol or glycerol.
6. The pharmaceutical composition of claim 1 or 2 wherein the vehicle consists essentially of polyol fatty acid esters containing over 90% saturated fatty acids.
7. The pharmaceutical composition of claim 1 or 2 wherein the vehicle consists essentially of polyol fatty acid esters containing fatty acids with a chain length of 6 to 14 C-atoms.
8. The pharmaceutical composition of claim 1 or 2 wherein the vehicle consists essentially of medium-chain triglycerides.
9. The pharmaceutical composition of claim 1 or 2 wherein the wetting agent consists essentially of polyol fatty acid esters containing as the polyol component 1,3-propanediol, glycerol, 1,2,3-butanetriol, 1,2,4-butanetriol, 1,3-butanediol, sorbitan or isopropanol.
10. The pharmaceutical composition of claim 1 or 2 wherein the wetting agent consists essentially of polyol fatty acid esters containing over 90% saturated fatty acids.
11. The pharmaceutical composition of claim 1 or 2 wherein the wetting agent consists essentially of polyol fatty acid esters containing fatty acids with a chain length of 6 to 14 C-atoms.
12. The pharmaceutical composition of claim 1 or 2 wherein the wetting agent consists essentially of glycerol monolaurate or glycerol monocaprylate.
13. The pharmaceutical composition of claim 1 or 2 wherein the wetting agent is present at a concentration of 0.1–5% (w/w).
14. The pharmaceutical composition of claim 1 or 2 wherein the pharmaceutical composition is free of any phosphatides.
15. The pharmaceutical composition of claim 1 or 2 wherein the pharmacologically active agent is present in crystalline form.
16. The pharmaceutical composition of claim 1 or 2 wherein the pharmacologically active agent is present in an amorphous form.
17. The pharmaceutical composition of claim 1 or 2 wherein the pharmacologically active agent is present in salt form.
18. The pharmaceutical composition of claim 1 wherein the active agent is present at a concentration of from 0.01 to 20% (w/v).
19. The pharmaceutical composition of claim 1 wherein the active agent is present at a concentration of from 0.02 to 5% (w/v).
20. The pharmaceutical composition of claim 3 wherein the active agent is selected from the group consisting of N-0923 (rotigotine), levodopa, cabergoline, ropinirole, pergolide and pramipexole.
21. The pharmaceutical composition of claim 1 or 20 wherein the composition consists of (a) the at least one pharmacologically active agent in its solid phase; (b) the vehicle consisting essentially of polyol fatty acid esters with an esterification level of over 80%; and (c) the wetting agent comprising polyol fatty acid esters with a monoester content of over 60%.
22. The pharmaceutical composition of claim 1 or 20 wherein the composition does not contain a fatty acid aluminum salt.
23. A kit comprising:
(a) a pharmaceutical composition of claim 1 or 2 ; and
(b) an injection device.
24. The pharmaceutical composition of claim 2 wherein the active agent is present at a concentration of from 0.01 to 20% (w/v).
25. The pharmaceutical composition of claim 2 wherein the active agent is present at a concentration of from 0.02 to 5% (w/v).
26. The pharmaceutical composition of claim 2 wherein the active agent is selected from the group consisting of N-0923 (rotigotine), levodopa, cabergoline, ropinirole, pergolide and pramipexole.
27. The pharmaceutical composition of claim 2 wherein the composition consists of(a) the at least one pharmacologically active agent in its solid phase; (b) the vehicle consisting essentially of polyol fatty acid esters with an esterification level of over 80%; and (c) the wetting agent comprising polyol fatty acid esters with a monoester content of over 60%.
28. The pharmaceutical composition of claim 2 wherein the composition does not contain a fatty acid aluminum salt.
29. The pharmaceutical composition of claim 1 wherein the active agent is selected from the group consisting of N-0923 (rotigotine), levodopa, cabergoline, ropinirole, pergolide and pramipexole.