Transdermal packaging membranes
Article side polymers useful in the packaging of transdermal patches are disclosed. These films do not absorb skin permeation enhancers that are contained in transdermal patches including keto acids such as levulinic acid or sulfoxides such as an alkyl sulfoxide, e.g., dimethyl sulfoxide. Using such polymeric film, multilayer pouch constructions can be manufactured which include other polymeric layers, such as aluminum foil for moisture and oxygen barrier properties, polyester for tear resistance and paper layers for optimal printing and design.
1. A package for storing a transdermal delivery patch that comprises an active pharmaceutical ingredient and (i) at least one skin penetration enhancer that is a keto acid and at least one additional enhancer that is a long chain monoglyceride or a C8-C16 ester of a short chain carboxylic acid, or (ii) at least one skin penetration enhancer that is a sulfoxide;
wherein the package is a pouch that fully encloses the transdermal delivery patch and comprises a multilayered packaging film having an article side polymer film that forms the innermost layer of the pouch, wherein the article side polymer film is heat sealable upon itself to effect the full enclosure of the transdermal patch and is selected from a thermoplastic fluoropolymer, amorphous polyethylene terephthalate, or polyacrylonitrile/methyl acrylate-acrylonitrile/butadiene graft copolymer;
wherein the article side polymer film absorbs less than about 0.5% by weight of the skin penetration enhancer(s) from the patch during a storage period of 6 months or longer at room temperature.
2. The package of claim 1 , wherein the transdermal delivery patch to be stored therein comprises the active pharmaceutical ingredient and at least one skin penetration enhancer that is a keto acid and at least one additional enhancer that is a long chain monoglyceride or a C8-C16 ester of a short chain carboxylic acid.
3. The package of claim 2 , wherein, in the transdermal delivery patch to be stored therein, the keto acid is levulinic acid (LA), the long chain monoglyceride is glycerol monooleate (GMO), and the C8-C16 ester of a short chain carboxylic acid is lauryl lactate (LL).
4. The package of claim 3 , wherein the amount of the first penetration enhancer in the transdermal delivery patch to be stored therein is about 0.5 wt % to about 10 wt % and the amount of the second penetration enhancer in the patch is about 0.5 wt % to about 10 wt %.
5. The package of claim 1 , wherein the transdermal delivery patch to be stored therein comprises an active pharmaceutical ingredient, at least one skin penetration enhancer that is a sulfoxide, and at least one additional skin penetration enhancer that is either a C8-C16 ester of a short chain carboxylic acid or a lower alkyl ester of a short chain carboxylic acid.
6. The package of claim 5 wherein, in the transdermal delivery patch to be stored therein, the sulfoxide is dimethyl sulfoxide (DMSO), C8-C16 ester of a short chain carboxylic acid is LL, and the lower alkyl ester of a short chain carboxylic acid is ethyl lactate (EL).
7. The package of claim 5 , wherein the enhancers in the transdermal delivery patch to be stored therein comprise DMSO, LL, EL, and a medium chain fatty acid.
8. The package of claim 7 , wherein the enhancers in the transdermal delivery patch to be stored therein comprise about 4% to about 12% of DMSO, about 4% to about 13% of LL, about 0.5% to about 2.5% of EL; and about 3% to about 9% of capric acid.
9. The package of claim 1 , wherein the transdermal delivery patch to be stored therein comprises a backing layer affixed to an adhesive polymer matrix, wherein the adhesive polymer matrix comprises:
a. the active pharmaceutical ingredient;
b. an adhesive polymer; and
c. (i) a first penetration enhancer selected from the group consisting of a keto acid and a pharmaceutically acceptable salt thereof and a second penetration enhancer selected from the group consisting of long chain monoglycerides and C8-C16 esters of short chain carboxylic acid or
(ii) a first penetration enhancer selected from the group consisting of alkyl sulfoxides and a second penetration enhancer selected from the group consisting of C8-C16 esters of a short chain carboxylic acid, lower alkyl esters of a short chain carboxylic acid, or both.
10. The package of claim 1 , wherein the article side polymer film is an acrylonitrile/methyl acrylate-acrylonitrile/butadiene graft copolymer.
11. The package of claim 1 , wherein the article side polymer film is an amorphous polyethylene terephthalate.
12. The package of claim 1 , wherein the article side polymer film is a thermoplastic fluoropolymer.
13. The package of claim 1 , within which is contained a transdermal delivery patch having a progestin and an estrogen as active pharmaceutical ingredients.
14. The package of claim 13 , wherein the progestin is levonorgestrel.
15. The package of claim 13 , wherein the estrogen is ethinyl estradiol.
16. An article of manufacture comprising a transdermal delivery patch that includes contraceptive hormones and (i) at least one skin penetration enhancer that is a keto acid and at least one additional enhancer that is a long chain monoglyceride or a C8-C16 ester of a short chain carboxylic acid, or (ii) at least one skin penetration enhancer that is a sulfoxide; wherein the transdermal delivery patch is contained within a package that fully encloses the transdermal delivery patch and comprises a multilayered packaging film having an article side polymer film that forms the innermost layer of the pouch, wherein the article side polymer film is heat sealable upon itself to effect the full enclosure of the transdermal patch and is selected from thermoplastic fluoropolymer, amorphous polyethylene terephthalate, or polyacrylonitrile/methyl acrylate-acrylonitrile/butadiene graft copolymer; wherein the article side polymer film absorbs less than about 0.5% by weight of the skin penetration enhancer(s) from the patch during a storage period of 6 months or longer at room temperature.
17. The article of manufacture of claim 16 , wherein the contraceptive hormones include a progestin and an estrogen.
18. The article of manufacture of claim 17 , wherein the progestin is levonorgestrel.
19. The article of manufacture of claim 18 , wherein the estrogen is ethinyl estradiol.