Transdermal delivery formulation

Abstract

The invention provides compositions and methods for delivering vitamin D to a human subject. In one embodiment the invention provides a transdermal patch for the transdermal administration of vitamin D comprising: (a) a backing layer that serves as the outer surface of the patch during use; (b) an adhesive drug reservoir layer for affixing the patch to human skin; and (c) a release liner, which upon removal exposes the adhesive drug reservoir layer. The adhesive drug reservoir layer can include vitamin D, a polymeric adhesive, an organic solvent, and a permeation enhancer.

1 . A transdermal patch for the transdermal administration of vitamin D comprising:
 (a) a backing layer that serves as the outer surface of the patch during use;   (b) an adhesive drug reservoir layer for affixing the patch to human skin; and   (c) a release liner, which upon removal exposes the adhesive drug reservoir layer;   wherein the adhesive drug reservoir layer consists of vitamin D, a polymeric adhesive, an organic solvent, and a permeation enhancer.   
     
     
         2 . The transdermal patch of  claim 1  wherein the vitamin D is cholecalciferol (vitamin D 3 ), calcifediol (25-hydroxyvitamin D 3 ), ergocalciferol (vitamin D 2 ), calcitriol, or calcipotriene. 
     
     
         3 . The transdermal patch of  claim 1  wherein the adhesive is a polyisobutylene adhesive, a silicone adhesive; or an acrylate adhesive. 
     
     
         4 . The transdermal patch of  claim 1  wherein the adhesive drug reservoir layer comprises about 1-10 wt. % of the vitamin D. 
     
     
         5 . The transdermal patch of  claim 1  wherein the adhesive drug reservoir layer comprises about 60-90 wt. % of the polymeric adhesive. 
     
     
         6 . The transdermal patch of  claim 1  wherein the adhesive drug reservoir layer comprises about 1-15 wt. % of the organic solvent. 
     
     
         7 . The transdermal patch of  claim 1  wherein the adhesive drug reservoir layer comprises about 1-15 wt. % of the permeation enhancer. 
     
     
         8 . The transdermal patch of  claim 1  wherein the vitamin D is cholecalciferol, the adhesive is an acrylate or polyisobutylene adhesive, the organic solvent comprises a triglyceride, and the permeation enhancer is transcutol. 
     
     
         9 . The transdermal patch of  claim 1  wherein the adhesive drug reservoir layer does not contain water. 
     
     
         10 . The transdermal patch of  claim 1  wherein the adhesive drug reservoir layer does not contain an organic base or an inorganic base. 
     
     
         11 . The transdermal patch of  claim 1  wherein the surface area of the adhesive drug reservoir layer of the patch is about 30 cm 2  to about 50 cm 2 . 
     
     
         12 . The transdermal patch of  claim 11  wherein the patch is formulated to deliver greater than 2,000 μg of vitamin D through 40 cm 2  of intact unbroken living skin in within 5 hours. 
     
     
         13 . The transdermal patch of  claim 11  wherein the patch is formulated to deliver greater than 20,000 μg of vitamin D through 40 cm 2  of intact unbroken living skin in within 24 hours. 
     
     
         14 . The transdermal patch of  claim 11  wherein the patch is formulated to contain about 4,000-5,000 I.U. of vitamin D. 
     
     
         15 . A transdermal patch for the transdermal administration of vitamin D 3  consisting of:
 (a) a backing layer that serves as the outer surface of the patch during use;   (b) an adhesive drug reservoir layer for affixing the patch to human skin; and   (c) a release liner, which upon removal exposes the adhesive drug reservoir layer;   wherein the adhesive drug reservoir layer consists of 1-10 wt. % of vitamin D 3 , 60-90 wt. % of a polymeric adhesive, an organic solvent, and 1-15 wt. % of transcutol.   
     
     
         16 . The transdermal patch of  claim 15  wherein the adhesive drug reservoir layer consists of 3 wt. % of vitamin D 3 , 80-85 wt. % of a polymeric adhesive, an organic solvent, and 5-10 wt. % of transcutol. 
     
     
         17 . A method for the transdermal delivery of vitamin D comprising removing the release liner of the transdermal patch of  claim 15  and applying the transdermal patch to intact unbroken living skin of a human subject, wherein the transdermal patch delivers greater than 0.75 μg/cm 2  of vitamin D to the subject within 5 hours. 
     
     
         18 . The method of  claim 17  wherein the transdermal patch is applied to a subject having a 25-hydroxyvitamin D 3  blood serum level of less than 30 ng/mL. 
     
     
         19 . The method of  claim 18  wherein the transdermal patch is applied to a subject having a 25-hydroxyvitamin D 3  blood serum level of about 1 ng/mL to about 25 ng/mL. 
     
     
         20 . The method of  claim 19  wherein the 25-hydroxyvitamin D 3  blood serum level of the subject increases to greater than 30 ng/mL within 5 hours. 
     
     
         21 . The method of  claim 17  wherein the transdermal patch is applied to the subject once per day for at least 5 days. 
     
     
         22 . The method of  claim 20  wherein the human subject has a 25-hydroxyvitamin D 3  blood serum level of less than 20 ng/mL. 
     
     
         23 . The method of  claim 22  wherein the human subject has cystic fibrosis, is older than 65 years of age, or has undergone bariatric surgery. 
     
     
         24 . A method of increasing the 25-hydroxyvitamin D 3  blood serum level of a human subject that has a vitamin D malabsorption condition comprising removing the release liner of the transdermal patch of  claim 1  and applying the transdermal patch to intact unbroken living skin of the human subject, wherein the 25-hydroxyvitamin D 3  blood serum level of the subject increases to greater than 20 ng/mL within 24 hours. 
     
     
         25 . The method of  claim 24  wherein the human subject that has a vitamin D malabsorption condition is a subject that has been diagnosed with cystic fibrosis.