Transdermal adhesive compositions, devices and methods

Patent metadata

Field	Value
Publication number	US-9375510-B2
Application number	US-201113811343-A
Country	US
Kind code	B2
Filing date	Jul 19, 2011
Priority date	Jul 21, 2010
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

A stable transdermal adhesive composition comprising: an adhesive comprising a washed polymerization reaction product of at least two ethylenically unsaturated monomers; and at least one pharmaceutically active compound which is susceptible to oxidative degradation; wherein the at least two ethylenically unsaturated monomers, if present in the adhesive as unreacted monomers, are present at a level of less than 200 ppm of total unreacted monomer, based upon the total weight of the adhesive, methods of making the composition, a transdermal drug delivery device using the composition, methods of making the device, and methods of delivery the pharmaceutically active compound are provided.

First claim

What is claimed is:

1. A method of making a stable transdermal adhesive composition comprising:
forming an adhesive by: providing a polymerization reaction product of at least two ethylenically unsaturated monomers; and wherein the polymerization reaction product is dissolved and/or dispersed in a first liquid;
separating at least a portion of the polymerization reaction product from the first liquid, wherein the separating step comprises washing the polymerization reaction product with at least one of methanol, isopropyl alcohol, mixtures of water and methanol, or mixtures of isopropyl alcohol and water, to provide a first washed polymerization reaction product;
dissolving or dispersing the first washed polymerization reaction product in a second liquid;
separating at least a portion of the first washed polymerization reaction product from the second liquid to provide a second washed polymerization reaction product;
wherein the at least two ethylenically unsaturated monomers, if present in the second washed polymerization reaction product, are present at a level of less than 200 ppm of total unreacted monomer, based upon the total weight of the second washed polymerization reaction product; and

combining the adhesive comprising the second washed polymerization reaction product with at least one pharmaceutically active compound which is susceptible to oxidative degradation to form a stable transdermal adhesive composition.

2. A method of making a stable transdermal adhesive composition comprising:
forming an adhesive by:
providing a polymerization reaction product of at least two ethylenically unsaturated monomers;
and wherein the polymerization reaction product is dissolved and/or dispersed in a first liquid;
separating at least a portion of the polymerization reaction product from the first liquid to provide a first washed polymerization reaction product, wherein the separating step comprises washing the polymerization reaction product with at least one of methanol, isopropyl alcohol, mixtures of water and methanol, or mixtures of isopropyl alcohol and water,;
dissolving or dispersing the first washed polymerization reaction product in a second liquid;
separating at least a portion of the first washed polymerization reaction product from the second liquid to provide a second washed polymerization reaction product;
dissolving or dispersing the second washed polymerization reaction product in a third liquid;
separating at least a portion of the second washed polymerization reaction product from the third liquid to provide a third washed polymerization reaction product;
wherein the at least two ethylenically unsaturated monomers, if present in the third washed polymerization reaction product, are present at a level of less than 200 ppm of total unreacted monomer, based upon the total weight of the second washed polymerization reaction product; and
combining the adhesive comprising the third washed polymerization reaction product with the at least one pharmaceutically active compound which is susceptible to oxidative degradation to form the stable transdermal adhesive composition.

3. The method of claim 1 , wherein the separating, in each instance, is carried out by adding a wash liquid to the dissolved polymerization reaction product, allowing polymerization reaction product to precipitate, and separating the precipitate from the liquid, to provide washed polymerization reaction product.

4. The method of claim 1 , further comprising polymerizing the at least two ethylenically unsaturated monomers dissolved in the first liquid to provide the polymerization reaction product dissolved and/or dispersed in the first liquid.

5. The method of claim 1 , wherein the at least two ethylenically unsaturated monomers, if present in the washed polymerization reaction product combined with the at least one pharmaceutically active compound, are present at a level of less than 100 ppm total unreacted monomer, based upon the total weight of the washed polymerization product.

6. The method of claim 1 , wherein the washed polymerization product combined with the at least one pharmaceutically active compound optionally comprises a free radical initiator, and wherein, if present, the free radical initiator is present at a level of less than 20 ppm, based upon the total weight of the washed polymerization reaction product.

7. The method of claim 1 , wherein the adhesive comprises the copolymerization product of at least one first monomer selected from the group consisting C 4 to C 12 alkyl acrylate monomers, C 4 to C 12 alkyl methacrylate monomers, and combinations thereof and at least one second monomer selected from the group consisting of acrylamide, N,N-diethylacrylamide, methacrylamide, vinyl acetate, vinyl alcohol, N-vinyl-2-pyrrolidone, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxpropyl acrylate, glyceryl acrylate, 2-ethoxyethyl acrylate, 2-ethoxyethoxyethyl acrylate, tetrahydrofurfuryl acrylate, acrylic acid, methacrylic acid, pyrrolidonylethyl acrylate, 2-carboxyethyl acrylate, and combinations thereof.

8. The method of claim 1 , wherein the at least one first monomer is selected from the group consisting of isooctyl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, 2-methylbutyl acrylate, butyl acrylate, and combinations thereof.

9. The method of claim 1 , wherein the adhesive polymer comprises a co-polymerization product of isooctyl acrylate, acrylamide, and vinyl acetate.

10. The method of claim 1 wherein the pharmaceutically active compound includes at least one group selected from the group consisting of tertiary amino, secondary amino, benzylic hydrogen-containing group, and combinations thereof.

11. The method of claim 1 , wherein the pharmaceutically active compound is selected from the group consisting of: rivastigmine ((S)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl]phenyl carbamate), buprenorphine, etidocaine, ropivacaine, clonidine, lidocaine, letrozole, fentanyl, indapamide, apomorphine, propylnorapomorphine, salbutamol, lisuride, dihydroergotamine, pergolide, terguride, proterguride, propranolol, imipramine, guanethidine, cyproheptadine and a pharmaceutically acceptable salt of any one of the preceding compounds.

12. The method of claim 11 , wherein the pharmaceutically active compound is (S)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl]phenyl carbamate or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein an antioxidant is not added to the stable transdermal adhesive composition.

14. The method of claim 1 , further comprising coating a backing sheet with the transdermal adhesive composition such that the transdermal adhesive composition covers at least a portion of a major surface of the backing sheet.

15. The method of claim 2 , wherein the separating, in each instance, is carried out by adding a wash liquid to the dissolved polymerization reaction product, allowing polymerization reaction product to precipitate, and separating the precipitate from the liquid, to provide washed polymerization reaction product.

16. The method of claim 2 , further comprising polymerizing the at least two ethylenically unsaturated monomers dissolved in the first liquid to provide the polymerization reaction product dissolved and/or dispersed in the first liquid.

17. The method of claim 2 , wherein the at least two ethylenically unsaturated monomers, if present in the washed polymerization reaction product combined with the at least one pharmaceutically active compound, are present at a level of less than 100 ppm total unreacted monomer, bas

Assignees

• Dizio James P
• Johnson Elizabeth E
• Wu Zheng Zhi
• Preszier Prince Amy
• 3M Innovative Properties Co

Inventors

• Dizio James P
• Johnson Elizabeth E
• Wu Zheng Zhi
• Preszier Prince Amy

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/27

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title

• C09J133/10

  Homopolymers or copolymers of methacrylic acid esters · CPC title

• C09J4/06 Primary

  {Organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond} in combination with a macromolecular compound other than an unsaturated polymer of groups C09J159/00 - C09J187/00 · CPC title