Penetrating topical pharmaceutical compositions containing N-(2-hydroxyethyl) pyrrolidone

• US 4,537,776 A
• Filed: 06/21/1983
• Issued: 08/27/1985
• Est. Priority Date: 06/21/1983
• Status: Expired due to Term

• Current Assignee: The Procter & Gamble Company
• Original Assignee: The Procter & Gamble Company
• Inventors: Cooper, Eugene R.
• Primary Examiner(s): Roberts, Elbert L.
• Application Number:
  US06/506,273
• Time in Patent Office: 798 Days
• Field of Search: 424/274, 424/230, 424/231, 424/308, 424/317
• US Class Current: 514/424
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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

Abstract

Topical pharmaceutical compositions comprising a pharmaceutically-active agent and a novel, penetration-enhancing vehicle or carrier are disclosed. The vehicle or carrier comprises a binary combination of N-(2-Hydroxyethyl) pyrrolidone and a "cell-envelope disordering compound". The compositions provide marked transepidermal and percutaneous delivery of the active selected. A method of treating certain pathologies and conditions responsive to the selected active, systemically or locally, is also disclosed.

Claims

1. A penetration-enhancing pharmaceutical composition for topical application, comprising:

(a) a safe and effective amount of a non-steroidal anti-inflammatory agent selected from the group consisting of salicylic acid, acetyl salicylic acid, methyl salicylate, glycol salicylate, salicylmides, benzyl-2,5-diacetoxybenzoic acid, ibuprofen, fulindac, naproxen, ketoprofen, etofenamate, phenylbutazone, indomethacin, piroxicam, and mixtures thereof;

(b) 0% to about 80% by weight of a solvent selected from ethanol or 2-propanol;

(c) 0% to about 80% by weight water; and

(d) about 10% to about 99.9% by weight of a penetration-enhancing vehicle consisting essentially of

(i) N-(2-hydroxyethyl)pyrrolidone, and

(ii) a cell-envelope disordering compound selected from the group consisting of methyl laurate, oleic acid, oleyl alcohol, monoolein, myristyl alcohol, and mixtures thereof;

wherein component (d)(i) and (d)(ii) are present in a ratio of (d)(i);

(d)(ii) of about 1;

5 to about 500;

1 by weight.

2. A composition according to claim 1 wherein component (d) is present at a level of about 15% to about 99.9% by weight.

3. A compound according to claim 2 wherein component (d) is present at a level of about 25% to about 99.9% by weight.

4. A composition according to claim 1 wherein components (d)(i) and (d)(ii) are present in a ratio of (d)(i):

(d)(ii) of about 5;

1 to about 100;

1 by weight.

5. A composition according to claim 4 wherein components (d)(i) and (d)(ii) are present in a ratio of (d)(i):

(d)(ii) of about 10;

1 to about 100;

1 by weight.

6. A composition according to claim 5 wherein components (d)(i) and (d)(ii) are present in a ratio of (d)(i):

(d)(ii) of about 15;

1 to about 100;

1 by weight.

7. A composition according to claim 1 wherein component (b) is present at a level of about 0% to about 70% by weight.

8. A composition according to claim 1 wherein component (d)(ii) is selected from the group consisting of methyl laurate, oleic acid, myristyl alcohol, and mixtures thereof.

9. A composition according to claim 8 wherein component (d)(ii) is methyl laurate.

10. A composition according to claim 8 wherein component (d)(ii) is oleic acid.

20. A composition according to claim 1 wherein the non-steroidal anti-inflammatory agent is present at a level of about 0.05% to about 10% by weight.

21. A composition according to claim 1 wherein said composition is substantially free of any single member of the saturated straight chain C₁₆ -C₂₀ normal fatty alcohols or saturated straight chain C₄ -C₂₀ mono- or dicarboxylic acids.

22. A composition according to claim 21 wherein said composition contains less than 3.5%, by weight, of any single saturated straight chain C₁₆ -C₂₀ normal fatty alcohols or saturated straight chain C₄ -C₂₀ mono- and dicarboxylic acids.

11. A penetration-enhancing pharmaceutical composition for topical application, comprising:

(a) about 0.01% to about 10%, by weight, of a non-steroidal anti-inflammatory agent selected from the group consisting of salicylic acid, acetyl salicylic acid, methyl salicylate, glycol salicylate, salicylmides, benzyl-2,5-diacetoxybenzoic acid, ibuprofen, fulindac, naproxen, ketoprofen, etofenamate, phenylbutazone, indomethacin, piroxicam, and mixtures thereof;

(b) 0% to about 80% by weight of a solvent selected from ethanol and 2-propanol;

(c) 0% to about 80% by weight water;

(d) about 10% to about 99.9% by weight of a penetration-enhancing vehicle consisting essentially of

(i) N-(2-hydroxyethyl)pyrrolidone, and

(ii) a cell-envelope disordering compound selected from the group consisting of methyl laurate, oleic acid, oleyl alcohol, monoolein, myristyl alcohol, and mixtures thereof;

wherein component (d)(i) and (d)(ii) are present in a ratio of (d)(i);

(d)(ii) of about 5;

1 to about 100;

1 by weight.

12. A composition according to claim 11 wherein component (d) is present at a level of about 15% to about 99.9% by weight.

13. A compound according to claim 12 wherein component (d) is present at a level of about 25% to about 99.9% by weight.

14. A composition according to claim 11 wherein components (d)(i) and (d)(ii) are present in a ratio of (d)(i):

(d)(ii) of about 10;

1 to about 100;

1 by weight.

15. A composition according to claim 14 wherein components (d)(i) and (d)(ii) are present in a ratio of (d)(i):

(d)(ii) of about 15;

1 to about 100;

1 by weight.

16. A composition according to claim 11 wherein component (b) is present at a level of about 0% to about 70% by weight.

17. A composition according to claim 11 wherein component (d)(ii) is selected from the group consisting of methyl laurate, oleic acid, myristyl alcohol, and mixtures thereof.

18. A composition according to claim 17 wherein component (d)(ii) is methyl laurate.

19. A composition according to claim 17 wherein component (d)(ii) is oleic acid.