Transdermal administration of tamsulosin

• US 8,784,879 B2
• Filed: 01/14/2010
• Issued: 07/22/2014
• Est. Priority Date: 01/14/2009
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Singh, Parminder, Lee, Eun Soo, Jain, Amit K.
• Primary Examiner(s): Oswecki, Jane C
• Application Number:
  US12/687,586
• Publication Number:
  US 20100291186A1
• Time in Patent Office: 1,650 Days
• Field of Search: 424/449, 514/603
• US Class Current: 424/449
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61P 13/08 of the prostate

Abstract

In an aspect of the invention, a composition for making a patch for the transdermal delivery of tamsulosin is provided. The composition comprises (a) at least about 1 wt % tamsulosin or a pharmaceutically acceptable salt of tamsulosin, (b) at least about 40 wt % polyisobutylene adhesive or hydrophobic synthetic rubber adhesive, (c) about 1-20 wt % of an aprotic solvent in which tamsulosin dissolves readily, (d) about 1-20 wt % of an unsaturated fatty acid or an alpha-hydroxy acid or a mixture of unsaturated fatty acids or alpha-hydroxy acids or of both unsaturated fatty acids and alpha-hydroxy acids, (e) a lipophilic permeation enhancer, and (f) a matrix modifier.

Claims

1. A composition for making a patch for the transdermal delivery of tamsulosin, the composition comprising (a) at least 1 wt % tamsulosin or a pharmaceutically acceptable salt of tamsulosin, (b) at least 40 wt % polyisobutylene adhesive or hydrophobic synthetic rubber adhesive, (c) about 1-20 wt % of an aprotic solvent in which tamsulosin dissolves, (d) about 1-20 wt % of an unsaturated fatty acid or an alpha-hydroxy acid or a mixture of unsaturated fatty acids or alpha-hydroxy acids or of both unsaturated fatty acids and alpha-hydroxy acids, (e) a lipophilic permeation enhancer, and (f) a matrix modifier.

2. The composition of claim 1, wherein at least a portion of the tamsulosin is present in the form of tamsulosin HCl.

3. The composition of claim 2, further comprising a neutralizing agent.

4. The composition of claim 3, wherein the neutralizing agent has a pKa equivalent to or higher than that of tamsulosin.

5. The composition of claim 3, wherein the neutralizing agent comprises an alkali hydroxide, an alkali salt, or an amine.

6. The composition of claim 5, wherein the neutralizing agent comprises sodium hydroxide or potassium hydroxide.

7. The composition of claim 5, wherein the neutralizing agent comprises an alkali salt selected from the group consisting of sodium carbonate, potassium carbonate, sodium silicate, and potassium silicate.

8. The composition of claim 4, wherein the neutralizing agent comprises substituted or non-substituted alkyl amines.

9. The composition of claim 8, wherein the neutralizing agent comprises ethanolamine and diethanolamine.

10. The composition of claim 3, wherein the neutralizing agent comprises sodium hydroxide.

11. The composition of claim 1, comprising at least 50 wt % polyisobutylene adhesive.

12. The composition of claim 1, comprising at least 50 wt % hydrophobic synthetic rubber adhesive.

13. The composition of claim 1, wherein the aprotic solvent is selected from the group consisting of dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide and combinations thereof.

14. The composition of claim 1, wherein the unsaturated fatty acid is a fatty acid with 11 to 21 carbons or a mixture of such fatty acids.

15. The composition of claim 1, wherein the unsaturated fatty acid comprises oleic acid, linoleic acid, or linolenic acid.

16. The composition of claim 1, wherein the alpha-hydroxy acid comprises an acid with 1 to 8 carbons with an alpha-hydroxyl group.

17. The composition of claim 1, wherein the alpha-hydroxy acid is selected from the group consisting of lactic acid, glycolic acid, malic, citric, alpha-hydroxy caprylic acid, alpha-hydroxybutyric acid and combinations thereof.

18. The composition of claim 1, wherein the lipophilic permeation enhancer is present at about 1-20 wt %.

19. The composition of claim 1, wherein the lipophilic permeation enhancer is selected from the group consisting of methyl laurate, propylene glycol monolaurate, glycerol monolaurate, glycerol monooleate, lauryl lactate, myristyl lactate and combinations thereof.

20. The composition of claim 1, wherein the matrix modifier is present at about 4-20 wt % of the composition.

21. The composition of claim 1, wherein the matrix modifier is selected from the group consisting of fumed silica, colloidal silicon dioxide, cross-linked polyvinylpyrrolidone, soluble polyvinylpyrrolidone, a cellulose derivative, polyacrylamide, polyacrylic acid, a polyacrylic acid salt, kaolin, bentonite and combinations thereof.

22. A patch comprising an adhesive matrix made by a process which comprises drying the composition of claim 1.

23. The patch of claim 22, wherein the adhesive matrix after said drying comprises at least 15 wt % liquid.

24. The patch of claim 22, wherein the adhesive matrix after drying has a coat weight between about 10 mg/cm² and 50 mg/cm².

25. The patch of claim 22, wherein the in vitro delivery range of tamsulosin is at least 1.7-12.7 μ

g/cm² per hr.

26. The patch of claim 22, wherein the adhesive matrix further comprises a nonwoven material.

27. The patch of claim 22, which in use over a 24-hour period of time is non-irritating or no more than mildly irritating.

28. The patch of claim 22, wherein the patch maintains self-adhesion for at least 7 days when it is worn.

35. A method of treating a urological condition, comprising administering to a patient suffering from or in danger of developing such a condition a transdermal patch comprising a tamsulosin-containing composition of claim 1.

40. The composition of claim 1, wherein at least a portion of the tamsulosin is present in the form of tamsulosin free base.

29. A method of manufacturing a transdermal drug-in-adhesive patch for delivery of tamsulosin, comprising the steps of (a) dissolving tamsulosin or a pharmaceutically acceptable salt of tamsulosin in an aprotic solvent, (b) combining the tamsulosin solution with a lipophilic permeation enhancer, an optional organic solvent, and an unsaturated fatty acid, (c) adding to the result of (b) a matrix modifier and homogenizing the resulting solution, (d) mixing the result of (c) with a polyisobutylene adhesive or hydrophobic synthetic rubber adhesive in a suitable solvent.

30. The method of claim 29, further comprising adding a neutralizing agent to the result of steps (a) or (b).

31. The method of claim 29, further comprising solvent casting the result of step (d).

32. The method of claim 29, resulting in a weight ratio of tamsulosin to the cast, dried matrix of at least 1 wt %.

33. The method of claim 29, where the aprotic solvent is selected from the group consisting of dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide and combinations thereof.

34. The method of claim 29, wherein the pharmaceutically acceptable salt of tamsulosin is tamsulosin hydrochloride.

36. A composition for making a patch for the transdermal delivery of an active agent which has poor solubility in an adhesive matrix, the composition comprising (a) at least 1 wt % the active agent or a pharmaceutically acceptable salt of the active agent, (b) at least 40 wt % polyisobutylene adhesive or hydrophobic synthetic rubber adhesive, (c) about 1-20 wt % of an aprotic solvent in which the active agent dissolves readily, (d) about 1-20 wt % of an unsaturated fatty acid or an alpha-hydroxy acid a mixture of unsaturated fatty acids or alpha-hydroxy acids or of both unsaturated fatty acids and alpha-hydroxy acids, (e) a lipophilic permeation enhancer, and (f) a matrix modifier.

37. A transdermal delivery system comprising tamsulosin or a pharmaceutically acceptable salt thereof and an alpha-hydroxy acid, wherein the molar ratio of alpha-hydroxy acid to tamsulosin is at least 0.05:

1.

38. A transdermal delivery system comprising tamsulosin or a pharmaceutically acceptable salt thereof and DMSO, wherein the ratio of the cumulative delivery of tamsulosin to cumulative delivery of DMSO is

at least 0.05 during the period from 72 to 120 hours, and

at least 0.08 during the period from 120 to 168 hours.

39. The transdermal delivery system of claim 38, wherein the ratio of the cumulative delivery of tamsulosin to the cumulative delivery of DMSO is

no more than about 0.15 in the first 72 hours,

no more than about 0.38 in the first 120 hours, and

no more than about 0.60 in the 168 hour period.