Method of making a high enhancer-loading polyacrylate formulation for transdermal applications
A polyacrylate formulation suitable for delivery of drug to through a body surface of an individual. By loading the drug and permeation enhancers at a high concentration into a polyacrylate proadhesive that has inadequate adhesive properties for typical adhesive application on the skin, a formulation with desirable adhesive characteristics and effective therapeutic properties can be made. The proadhesive has higher glass transition temperature than typical pressure sensitive adhesives.
1. A method of making an adhesive reservoir for transdermal drug delivery, comprising:
providing an acrylate polymer capable of dissolving a drug and permeation enhancer in a combined dissolved amount in the acrylate polymer of at least 30 wt %, the acrylate polymer having a T g of greater than −10° C. without the at least one permeation enhancer and without the at least one drug, the acrylate polymer comprising a soft monomer component of no more than 40 wt %, 40 wt % or more of a hard monomer component, at least a portion of the hard monomer component being hard polar functional monomer, and 10 to 35 wt % of a polar functional monomer component, at least a portion of the polar functional monomer component being hard polar functional monomer,
incorporating the drug and permeation enhancer in the acrylate polymer in an amount of at least 30 wt % to result in a single phase reservoir so that dissolved drug and permeation enhancer constitute together more than 30 wt % and the acrylate polymer constitutes 45 wt % to 80 wt % in solids of the reservoir, wherein the reservoir is applicable as a pressure sensitive adhesive to a body surface.
2. The method of claim 1 wherein the reservoir with the drug and permeation enhancer dissolved therein has a glass transition temperature T g of −10 to −20° C. whereas the acrylate polymer without drug and without permeation enhancer has a T g of greater than −10° C. and a creep compliance of 6×10 −5 cm 2 /dyn to 2×10 −6 cm 2 /dyn.
3. The method of claim 1 wherein the acrylate polymer includes (i) 40 to 50 wt % of soft alkyl acrylate monomer component, in which each soft alkyl acrylate monomer therein has a homopolymer T g of −80 to −20° C., (ii) 40 to 60 wt % of nonfunctional hard modifying monomer component, in which each hard modifying monomer has a homopolymer T g of 0 to 250° C., and (iii) 10 to 30 wt % of polar functional monomer component, wherein the soft monomer is an alkyl acrylate monomer having 4 to 10 carbon atoms in the alkyl group.
4. The method of claim 1 wherein the acrylate polymer includes a soft acrylate monomer selected from the group consisting of butyl, hexyl, 2-ethylhexyl, octyl, and dodecyl acrylates and isomers thereof.
5. The method of claim 1 wherein the acrylate polymer includes 40 to 50 wt % of soft alkyl acrylate monomer component having a homopolymer T g of less than −20° C.
6. The method of claim 1 wherein the acrylate polymer has a T g of 0 to −10° C. if without drug and permeation enhancer, and the reservoir with the dissolved drug and permeation enhancer has a T g of −10 to −20° C., a creep compliance of 1×10 −4 cm 2 /dyn to 6×10 −4 cm 2 /dyn and storage modulus of 1×10 5 dyn/cm 2 to 8×10 5 dyn/cm 2 .
7. The method of claim 1 comprising incorporating permeation enhancer and a basic drug in the acrylate polymer forming a single phase reservoir, wherein the acrylate polymer without the drug and without the permeation enhancer has a T g of 0 to −10° C., storage modulus of 8×10 5 dyn/cm 2 or above, and the reservoir with the drug and permeation enhancer has a T g of −10 to −20° C., a creep compliance of 1×10 −4 cm 2 /dyn to 6×10 −4 cm 2 /dyn and storage modulus of 1×10 5 dyn/cm 2 to 8×10 5 dyn/cm 2 .
8. The method of claim 1 comprising providing the acrylate polymer having monomer components consisting essentially of 50 to 60 wt % vinyl acetate, 10-20 wt % hydroxyethyl acrylate, and 20-40 wt % 2-ethylhexyl acrylate.
9. The method of claim 1 comprising providing the acrylate polymer having monomer components consisting essentially of 55 to 65 wt % butyl acrylate, 5 to 15 wt % t-octyl acrylamide, 20 to 30 wt % hydroxyethyl or hydroxypropyl acrylate and 5 to 10 wt % acidic monomer.
10. The method of claim 1 comprising polymerizing without crosslinking to form the acrylate polymer wherein the acrylate polymer has monomer components consisting essentially of either (i) 50 to 60 wt % vinyl acetate, 10-20 wt % hydroxyethyl acrylate, and 20-40 wt % 2-ethylhexyl acrylate; or (ii) 55 to 65 wt % butyl acrylate, 5 to 15 wt % t-octyl acrylamide, 20 to 30 wt % hydroxyethyl or hydroxypropyl acrylate and 5 to 10 wt % acidic monomer; and wherein the acrylate polymer without the drug and permeation enhancer has a T g of greater than −10° C.