Preparation of hydrophilic pressure sensitive adhesives having optimized adhesive properties

• US 6,576,712 B2
• Filed: 07/06/2001
• Issued: 06/10/2003
• Est. Priority Date: 07/07/2000
• Status: Expired

• Current Assignee: AV Topchiev Institute of Petrochemical Synthesis, Corium, Inc.
• Original Assignee: AV Topchiev Institute of Petrochemical Synthesis, Corium International, Inc.
• Inventors: Cleary, Gary W., Feldstein, Mikhail M., Chalykh, Anatoly E., Plate, Nicolai A.
• Primary Examiner(s): Seidleck, James J.
• Assistant Examiner(s): Asinovsky, Olga
• Application Number:
  US09/900,697
• Publication Number:
  US 20020037977A1
• Time in Patent Office: 704 Days
• Field of Search: 525/326.9, 525/384, 524/386, 424/448
• US Class Current: 525/326.9
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61L 15/58 Adhesives
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 33/00 Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 39/04 Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member

Abstract

A method for preparing hydrophilic pressure sensitive adhesive (PSA) compositions is provided, wherein the method enables preparation of adhesives having a particular, optimized degree of adhesion. That is, the hydrophilic PSA is comprised of a hydrophilic polymer and a complementary short-chain plasticizing agent, wherein the hydrophilic polymer and plasticizing agent are capable of hydrogen bonding or electrostatic bonding to each other and are present in a ratio that optimizes key characteristics of the adhesive composition, such as adhesive strength, cohesive strength and hydrophilicity. The adhesive is useful in a wide variety of contexts, e.g., as a biomedical adhesive for application to the skin or other body surface, and as such finds utility in the areas of drug delivery systems (e.g., topical, transdermal, transmucosal, iontophoretic), medical skin coverings and wound healing products and biomedical electrodes.

Claims

1. A method of preparing an adhesive composition having an optimized degree of adhesion, comprising:

(a) preparing a plurality of compositions each comprised of a hydrophilic polymer having a glass transition temperature T_{g pol} admixed with a plasticizer miscible therewith and having a glass transition temperature T_{g pl} and capable of covalently or noncovalently crosslinking the hydrophilic polymer, wherein the weight fraction of the hydrophilic polymer in each composition is w_pol, and the weight fraction of the plasticizer in each composition is w_pl;

(b) calculating predicted glass temperatures T_{g predicted} for each composition using the Fox equation (1) $\begin{array}{cc}\frac{1}{T_{g<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{predicted}}}=\frac{w_{\mathrm{pol}}}{T_{g_{\mathrm{pol}}}}+\frac{w_{\mathrm{pl}}}{T_{g_{\mathrm{pl}}}}& \left(1\right)\end{array}$

and plotting T_{g predicted} versus w_pl for each composition;

(c) determining the glass transition temperature T_{g actual} for each composition, and plotting T_{g actual} versus w_pl for each composition;

(d) identifying the region of the plots of (b) and (c) wherein T_{g actual} is less than T_{g predicted};

such that there is a negative deviation from T_{g predicted};

(e) within the region identified in (d), identifying the optimum weight fraction of plasticizer w_{pl optimum} at which the negative deviation from T_{g predicted} is at a maximum; and

(f) admixing a monomeric precursor to the hydrophilic polymer and the plasticizer under polymerizing conditions to provide an adhesive composition having an optimized degree of adhesion, wherein the weight fraction of plasticizer in the composition is w_{pl optimum}, and the weight fraction of the hydrophilic polymer in the composition is 1-w_{pl optimum}.

2. The method of claim 1, wherein the plasticizer is capable of covalently crosslinking the hydrophilic polymer.

3. The method of claim 1, wherein the plasticizer is capable of noncovalently crosslinking the hydrophilic polymer.

4. The method of claim 1, wherein the plasticizer is capable of crosslinking the hydrophilic polymer by hydrogen bonding thereto.

9. The method of claim 1, wherein the difference between T_{g pol} and T_{g pl} is at least about 50°

C., such that T_{g actual} for each composition is determined solely by T_{g pl}.

10. The method of claim 2, wherein the difference between T_{g pol} and T_{g pl} is at least about 50°

C., such that T_{g actual} for each composition is determined solely by T_{g pl}.

11. The method of claim 1, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinylamine, and copolymers and blends thereof.

12. The method of claim 11, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), and copolymers and blends thereof.

13. The method of claim 12, wherein the hydrophilic polymer is a poly(N-vinyl lactam).

14. The method of claim 13, wherein the hydrophilic polymer is a poly(N-vinyl lactam) homopolymer.

15. The method of claim 14, wherein the poly(N-vinyl lactam) is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl caprolactam, and blends thereof.

16. The method of claim 15, wherein the poly(N-vinyl lactam) is polyvinyl pyrrolidone.

17. The method of claim 15, wherein the poly(N-vinyl lactam) is polyvinyl caprolactam.

18. The method of claim 12, wherein the hydrophilic polymer is a poly(N-vinyl amide).

19. The method of claim 18, wherein the poly(N-vinyl amide) is polyacetamide.

20. The method of claim 12, wherein the hydrophilic polymer is a poly(N-alkylacrylamide).

21. The method of claim 20, wherein the poly(N-alkylacrylamide) is polymethacrylamide or poly(N-isopropyl acrylamide).

22. The method of claim 1, wherein the hydrophilic polymer has a weight average molecular weight in the range of approximately 100,000 to 2,000,000.

23. The method of claim 22, wherein the hydrophilic polymer has a weight average molecular weight in the range of approximately 500,000 to 1,500,000.

24. The method of claim 1, wherein T_{g pl} is in the range of approximately −

100°

to −

30°

C.

25. The method of claim 24, wherein the melting temperature of the plasticizer is lower than about 50°

C.

26. The method of claim 1, wherein the plasticizing agent has a molecular weight in the range of about 45 to 800.

27. The method of claim 26, wherein the plasticizing agent has a molecular weight in the range of about 45 to 600.

28. The method of claim 24, wherein the plasticizing agent has a molecular weight in the range of about 300 to 600.

29. The method of claim 26, wherein the plasticizing agent is selected from the group consisting of of polyalcohols, monomeric and oligomeric alkylene glycols, polyalkylene glycols, carboxyl-teminated polyalkylene glycols, amino-terminated polyalkylene glycols, ether alcohols, alkane diols and carbonic diacids.

30. The method of claim 29, wherein the plasticizing agent is selected from the group consisting of polyalkylene glycols and carboxyl-terminated polyalkylene glycols.

31. The method of claim 30, wherein the plasticizing agent is selected from the group consisting of polyethylene glycol and carboxyl-terminated polyethylene glycol.

32. The method of claim 31, wherein the plasticizing agent is polyethylene glycol.

33. The method of claim 1, wherein the adhesive composition further includes a photoinitator, and, following step (e), the adhesive composition is crosslinked using radiation.

34. The method of claim 1, wherein step (e) further includes admixing the hydrophilic polymer and the plasticizing agent with at least one chemical crosslinking agent that covalently crosslinks the adhesive composition.

35. The method of claim 34, wherein the at least one chemical crosslinking agent is selected from the group consisting of dipentaerythritol pentaacrylate, ethylene glycol dimethacrylate, and triethylene glycol dimethacrylate.

36. The method of claim 35, wherein the weight ratio of the chemical crosslinking agent to the hydrophilic polymer is below 5%.

37. The method of claim 1, wherein, following step (e), the adhesive composition is crosslinked using heat.

38. The method of any one of claims 33, 34 or 36, wherein the crosslinking density of the crosslinked adhesive composition provides a swell ratio in the range of approximately 20 to approximately 60.

5. A method of preparing an adhesive composition having an optimized degree of adhesion, comprising:

(a) preparing a plurality of compositions each comprised of a hydrophilic polymer having a glass transition temperature T_{g pol} admixed with a plasticizer miscible therewith and having a glass transition temperature T_{g pl} and capable of covalently or noncovalently crosslinking the hydrophilic polymer, wherein the weight fraction of the hydrophilic polymer in each composition is w_pol, and the weight fraction of the plasticizer in each composition is w_pl, such that w_pol is equal to 1-w_pl;

(b) calculating predicted glass temperatures T_{g predicted} for each composition using the Fox equation (1) $\begin{array}{cc}\frac{1}{T_{g<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{predicted}}}=\frac{w_{\mathrm{pol}}}{T_{g_{\mathrm{pol}}}}+\frac{w_{\mathrm{pl}}}{T_{g_{\mathrm{pl}}}}& \left(1\right)\end{array}$

and plotting T_{g predicted} versus w_pl for each composition;

(c) determining the glass transition temperature T_{g actual} for each composition, and plotting T_{g actual} versus w_pl for each composition;

(d) identifying the region of the plots of (b) and (c) wherein T_{g actual} has a predetermined deviation from T_{g predicted}; and

(e) admixing a monomeric precursor to the hydrophilic polymer and the plasticizer under polymerizing conditions to provide an adhesive composition having a desired degree of adhesion, wherein the weight percent of plasticizer in the composition corresponds to a value within the region identified in section (d).

6. The method of claim 5, wherein the plasticizer is capable of covalently crosslinking the hydrophilic polymer.

7. The method of claim 5, wherein the plasticizer is capable of noncovalently crosslinking the hydrophilic polymer.

8. The method of claim 5, wherein the plasticizer is capable of crosslinking the hydrophilic polymer by hydrogen bonding thereto.

39. A hydrophilic pressure sensitive adhesive composition comprising (1) a hydrophilic polymer having a glass transition temperature T_{g pol}, and (2) a complementary hydroxyl-terminated or carboxyl-terminated short-chain plasticizing agent having a glass transition temperature T_{g pl} and capable of hydrogen bonding or electrostatic bonding to the hydrophilic polymer, wherein the weight ratio of hydrophilic polymer to complementary short-chain plasticizing agent is selected so to provide a predetermined deviation in (a) the actual glass transition temperature T_{g actual} of the composition from (b) the predicted glass transition temperature T_{g predicted} calculated for the composition using Fox equation (1) $\begin{array}{c}\frac{1}{T_{g}}\end{array}$

 



predicted=wpolTgpol+wplTgpl.(1)

40. The composition of claim 39, wherein the predetermined deviation is the maximum negative deviation.

43. The composition of any one of claims 39, 41 or 42, wherein the adhesive composition is substantially nonaqueous.

44. The composition of claim 39, wherein the difference between T_{g pol} and T_{g pl} is at least about 50°

C., such that T_{g actual} for each composition is determined solely by T_{g pl}.

45. The composition of claim 39, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinylamine, and copolymers and blends thereof.

46. The composition of claim 45, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), and copolymers and blends thereof.

47. The composition of claim 46, wherein the hydrophilic polymer is a poly(N-vinyl lactam).

48. The composition of claim 47, wherein the hydrophilic polymer is a poly(N-vinyl lactam) homopolymer.

49. The composition of claim 48, wherein the poly(N-vinyl lactam) is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl caprolactam, and blends thereof.

50. The composition of claim 49, wherein the poly(N-vinyl lactam) is polyvinyl pyrrolidone.

51. The composition of claim 49, wherein the poly(N-vinyl lactam) is polyvinyl caprolactone.

52. The composition of claim 39, wherein the hydrophilic polymer is a poly(N-vinyl amide).

53. The composition of claim 52, wherein the poly(N-vinyl amide) is polyacetamide.

54. The composition of claim 39, wherein the hydrophilic polymer is a poly(N-alkylacrylamide).

55. The composition of claim 54, wherein the poly(N-alkylacrylamide) is polymethacrylamide or poly(N-isopropyl acrylamide).

56. The composition of claim 39, wherein the hydrophilic polymer has a weight average molecular weight in the range of approximately 100,000 to 2,000,000.

57. The composition of claim 56, wherein the hydrophilic polymer has a weight average molecular weight in the range of approximately 500,000 to 1,500,000.

58. The composition of claim 39, wherein T_{g pl} is in the range of approximately −

100°

to −

30°

C.

59. The composition of claim 58, wherein the melting temperature of the plasticizer is lower than about 50°

C.

60. The composition of claim 39, wherein the plasticizing agent has a molecular weight in the range of about 45 to 800.

61. The composition of claim 60, wherein the plasticizing agent has a molecular weight in the range of about 45 to 600.

62. The composition of claim 61, wherein the plasticizing agent has a molecular weight in the range of about 300 to 600.

63. The composition of claim 60, wherein the plasticizing agent is selected from the group consisting of of polyalcohols, monomeric and oligomeric alkylene glycols, polyalkylene glycols, carboxyl-teminated polyalkylene glycols, amino-terminated polyalkylene glycols, ether alcohols, alkane diols and carbonic diacids.

64. The composition of claim 63, wherein the plasticizing agent is selected from the group consisting of polyalkylene glycols and carboxyl-terminated polyalkylene glycols.

65. The composition of claim 64, wherein the plasticizing agent is selected from the group consisting of polyethylene glycol and carboxyl-terminated polyethylene glycol.

66. The composition of claim 65, wherein the plasticizing agent is polyethylene glycol.

67. The composition of claim 39, wherein the composition is covalently crosslinked.

68. The composition of claim 67, wherein the crosslinking density of the crosslinked adhesive composition provides a swell ratio in the range of approximately 20 to approximately 60.

41. A hydrophilic, substantially nonaqueous pressure sensitive adhesive composition comprising (a) a hydrophilic polymer, and (b) a complementary hydroxyl-terminated or carboxyl-terminated short-chain plasticizing agent capable of hydrogen bonding or electrostatic bonding to the hydrophilic polymer,

wherein the ratio of hydrogen bonding to covalent crosslinks is selected to optimize adhesive strength, cohesive strength, and hydrophilicity;

wherein the plasticizing agent decreases the glass transition temperature T_g of the hydrophilic composition according to Fox equation (1) $\begin{array}{cc}\frac{1}{T_{g<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{predicted}}}=\frac{w_{\mathrm{pol}}}{T_{g_{\mathrm{pol}}}}+\frac{w_{\mathrm{pl}}}{T_{g_{\mathrm{pl}}}}& \left(1\right)\end{array}$

wherein T_{g predicted} is the predicted glass transition temperature of the hydrophilic polymer/plasticizer composition, w_pol is the weight fraction of the hydrophilic polymer in the composition, w_pl is the weight fraction of the plasticizer in the composition, T_{g pol} is the glass transition temperature of the hydrophilic polymer, and T_{g pl} is the glass transition temperature of the plasticizer; and

wherein maximum adhesiveness is achieved at a point of maximum negative deviation from T_{g predicted}.

42. A hydrophilic pressure sensitive adhesive composition comprising (a) a hydrophilic polymer and (b) a complementary hydroxyl-terminated or carboxyl-terminated short-chain plasticizing agent capable of hydrogen bonding or electrostatic bonding to the hydrophilic polymer,

wherein the hydrophilic polymer and the plasticizing agent are crosslinked to a predetermined extent, and the extent of crosslinking and the ratio of the hydrophilic polymer to the plasticizing agent are selected to optimize the hydrophilicity, adhesive strength and cohesive strength of the composition;

wherein the plasticizing agent decreases the glass transition temperature T_g of the hydrophilic composition according to Fox equation (1) $\begin{array}{cc}\frac{1}{T_{g<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{predicted}}}=\frac{w_{\mathrm{pol}}}{T_{g_{\mathrm{pol}}}}+\frac{w_{\mathrm{pl}}}{T_{g_{\mathrm{pl}}}}& \left(1\right)\end{array}$

wherein T_{g predicted} is the predicted glass transition temperature of the hydrophilic polymer/plasticizer composition, w_pol is the weight fraction of the hydrophilic polymer in the composition, w_pl is the weight fraction of the plasticizer in the composition, T_{g pol} is the glass transition temperature of the hydrophilic polymer, and T_{g pl} is the glass transition temperature of the plasticizer; and

wherein maximum adhesiveness is achieved at a point of maximum negative deviation from T_{g predicted}.

69. A therapeutic system for the topical or transdermal administration of a pharmacologically active agent, comprising:

(A) a drug reservoir comprising (1) a substantially nonaqueous pressure sensitive adhesive matrix of a hydrophilic polymer having a glass transition temperature T_{g pol}, and a complementary hydroxyl-terminated or carboxyl-terminated short-chain plasticizing agent having a glass transition temperature T_{g pl} and capable of hydrogen bonding or electrostatic bonding to the hydrophilic polymer, wherein the weight ratio of hydrophilic polymer to complementary short-chain plasticizing agent is selected so to provide a predetermined deviation in (a) the actual glass transition temperature T_{g actual} of the composition from (b) the predicted glass transition temperature T_{g predicted} for the composition calculated using Fox equation (1) $\begin{array}{cc}\frac{1}{T_{g<br><br>\text{\hspace{1em}<br><br>}<br><br>\mathrm{predicted}}}=\frac{w_{\mathrm{pol}}}{T_{g_{\mathrm{pol}}}}+\frac{w_{\mathrm{pl}}}{T_{g_{\mathrm{pl}}}},& \left(1\right)\end{array}$

 

and (2) a therapeutically effective amount of the active agent; and

(B) a backing layer laminated to the drug reservoir that serves as the outer surface of the device during use.

70. The system of claim 69, wherein the predetermined deviation is the maximum negative deviation.

71. The system of claim 69, wherein the hydrophilic polymer is comprised of repeating units resulting from polymerization of an N-vinyl lactam monomer, a carboxy vinyl monomer, a vinyl ester monomer, an ester of a carboxy vinyl monomer, a vinyl amide monomer, a hydroxy vinyl monomer, or a combination thereof.

72. The system of claim 71, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinylamine, and copolymers and blends thereof.

73. The system of claim 72, wherein the hydrophilic polymer is selected from the group consisting of poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), and copolymers and blends thereof.

74. The system of claim 73, wherein the hydrophilic polymer is a poly(N-vinyl lactam).

75. The system of claim 74, wherein the hydrophilic polymer is a poly(N-vinyl lactam) homopolymer.

76. The system of claim 75, wherein the poly(N-vinyl lactam) is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl caprolactam, and blends thereof.

77. The system of claim 76, wherein the poly(N-vinyl lactam) is polyvinyl pyrrolidone.

78. The system of claim 76, wherein the poly(N-vinyl lactam) is polyvinyl caprolactone.

79. The system of claim 73, wherein the hydrophilic polymer is a poly(N-vinyl amide).

80. The system of claim 79, wherein the poly(N-vinyl amide) is polyacetamide.

81. The system of claim 73, wherein the hydrophilic polymer is a poly(N-alkylacrylamide).

82. The system of claim 81, wherein the poly(N-alkylacrylamide) is polymethacrylamide or poly(N-isopropyl acrylamide).

83. The system of claim 69, wherein the hydrophilic polymer has a weight average molecular weight in the range of approximately 100,000 to 2,000,000.

84. The system of claim 83, wherein the hydrophilic polymer has a weight average molecular weight in the range of approximately 500,000 to 1,500,000.

85. The system of claim 69, wherein T_{g pl} is at least 50°

C. below T_{g pol}.

86. The system of claim 85, wherein T_{g pl} is in the range of approximately −

100°

to −

30°

C.

87. The system of claim 69, wherein the melting temperature of the plasticizer is lower than about 50°

C.

88. The system of claim 87, wherein the plasticizing agent has a molecular weight in the range of about 45 to 800.

89. The system of claim 88, wherein the plasticizing agent has a molecular weight in the range of about 45 to 600.

90. The system of claim 89, wherein the plasticizing agent has a molecular weight in the range of about 300 to 600.

91. The system of claim 88, wherein the plasticizing agent is selected from the group consisting of of polyalcohols, monomeric and oligomeric alkylene glycols, polyalkylene glycols, carboxyl-teminated polyalkylene glycols, amino-terminated polyalkylene glycols, ether alcohols, alkane diols and carbonic diacids.

92. The system of claim 91, wherein the plasticizing agent is selected from the group consisting of polyalkylene glycols and carboxyl-terminated polyalkylene glycols.

93. The system of claim 92, wherein the plasticizing agent is selected from the group consisting of polyethylene glycol and carboxyl-terminated polyethylene glycol.

94. The system of claim 93, wherein the plasticizing agent is polyethylene glycol.

95. The system of claim 69, wherein the composition is covalently crosslinked.

96. The system of claim 95, wherein the crosslinking density of the crosslinked adhesive composition provides a swell ratio in the range of approximately 20 to approximately 60.

97. The system of claim 69, wherein the backing layer is non-occlusive.

98. The system of claim 69, wherein the backing layer is occlusive.