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

Claim 2

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.

Claim 3

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

Claim 4

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

Claim 5

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.

Claim 6

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.

Claim 7

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.

Claim 8

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

Claim 9

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.

Claim 10

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

Claim 11

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

Claim 12

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.

Claim 13

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.

Claim 14

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

Claim 15

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

Claim 16

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.

Claim 17

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.

Claim 18

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

Claim 19

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.

Claim 20

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

Claim 21

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

Claim 22

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.

Claim 23

A composition according to claim 1 wherein said composition is substantially free of any single member of the saturated straight chain C 16 -C 20 normal fatty alcohols or saturated straight chain C 4 -C 20 mono- or dicarboxylic acids.

Claim 24

A composition according to claim 21 wherein said composition contains less than 3.5%, by weight, of any single saturated straight chain C 16 -C 20 normal fatty alcohols or saturated straight chain C 4 -C 20 mono- and dicarboxylic acids.