Adhesive peel-forming formulations for dermal delivery of drugs and methods of using the same
First Claim
1. An adhesive peel-forming formulation for dermal delivery of a drug, comprising:
- a) a drug;
b) a solvent vehicle, comprising;
i) a volatile solvent system including one or more volatile solvent, and ii) a non-volatile solvent system including one or more non-volatile solvent, wherein the non-volatile solvent system has a solubility with respect to the drug that is within a window of operable solubility such that the drug is deliverable at therapeutically effective rates over a sustained period of time; and
c) a peel-forming agent, wherein the formulation has a viscosity suitable for application and adhesion to a skin surface prior to evaporation of the volatile solvent system, and wherein the formulation applied to the skin surface forms a solidified peelable layer after at least partial evaporation of the volatile solvent system, wherein the drug continues to be delivered after the volatile solvent system is substantially evaporated.
8 Assignments
0 Petitions
Accused Products
Abstract
The present invention is drawn to adhesive peel-forming formulations for dermal delivery of a drug. The formulation can include a drug, a solvent vehicle, and a peel-forming agent. The solvent vehicle can include a volatile solvent system having one or more volatile solvent, and a non-volatile solvent system having one or more non-volatile solvent, wherein the non-volatile solvent system has a solubility for the drug that is within a window of operable solubility for the drug such that the drug can be delivered at therapeutically effective rates over a sustained period of time. The formulation can have a viscosity suitable for application to a skin surface prior to evaporation of the volatile solvents system. When applied to the skin, the formulation can form a solidified peelable layer after at least a portion of the volatile solvent system is evaporated.
-
Citations
109 Claims
-
1. An adhesive peel-forming formulation for dermal delivery of a drug, comprising:
-
a) a drug;
b) a solvent vehicle, comprising;
i) a volatile solvent system including one or more volatile solvent, and ii) a non-volatile solvent system including one or more non-volatile solvent, wherein the non-volatile solvent system has a solubility with respect to the drug that is within a window of operable solubility such that the drug is deliverable at therapeutically effective rates over a sustained period of time; and
c) a peel-forming agent, wherein the formulation has a viscosity suitable for application and adhesion to a skin surface prior to evaporation of the volatile solvent system, and wherein the formulation applied to the skin surface forms a solidified peelable layer after at least partial evaporation of the volatile solvent system, wherein the drug continues to be delivered after the volatile solvent system is substantially evaporated. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55)
-
-
56. A method of dermally delivering a drug, comprising:
-
a) applying an adhesive peel-forming formulation to a skin surface of a subject, said adhesive peel-forming formulation, comprising;
i) a drug;
ii) a solvent vehicle, comprising;
a volatile solvent system including one or more volatile solvent, and a non-volatile solvent system having one or more non-volatile solvent, wherein the non-volatile solvent system has a solubility with respect to the drug that is within a window of operable solubility such that the drug can be delivered at therapeutically effective rates over a sustained period of time; and
iii) a peel-forming agent, wherein the formulation has a viscosity suitable for application and adhesion to a skin surface prior to evaporation of the volatile solvent system, and wherein the formulation applied to the skin surface forms a solidified peelable layer after at least partial evaporation of the volatile solvent system, wherein the drug continues to be delivered after the volatile solvent system is substantially evaporated; and
b) dermally delivering the drug from the solidified peelable layer to the subject at therapeutically effective rates over a sustained period of time. - View Dependent Claims (57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84)
-
-
85. A method of preparing an adhesive peel-forming formulation for dermal drug delivery, comprising:
-
a) selecting a drug suitable for dermal delivery;
b) selecting non-volatile solvent system consisting essentially of one non-volatile solvent that has a solubility with respect to the drug within a window of operable solubility; and
c) formulating the drug and the non-volatile solvent into an adhesive peel-forming formulation that further includes a peel-forming agent and a volatile solvent system including at least one volatile solvent, said adhesive peel-forming formulation having a viscosity suitable for application to a skin surface prior to evaporation of the volatile solvent system, and wherein the formulation applied to the skin surface forms a solidified peelable layer after at least a portion of the volatile solvent system is evaporated, and wherein the drug continues to be delivered at therapeutically effective rates after the volatile solvent system is substantially evaporated. - View Dependent Claims (86, 87)
-
-
88. A method of preparing an adhesive peel-forming formulation for dermal drug delivery, comprising:
-
a) selecting a drug suitable for dermal delivery;
b) forming a non-volatile solvent system by selecting at least two non-volatile solvents according to a ratio that positions the solubility of the drug in the non-volatile solvent system within a window of operable solubility; and
c) formulating the drug and the non-volatile solvent system into an adhesive peel-forming formulation that further includes a peel-forming agent and a volatile solvent system including at least one volatile solvent, said adhesive peel-forming formulation having a viscosity suitable for application to a skin surface prior to evaporation of the volatile solvent system, and wherein the formulation applied to the skin surface forms a solidified peelable layer after at least a portion of the volatile solvent system is evaporated, and wherein the drug continues to be delivered at therapeutically effective rates after the volatile solvent system is substantially evaporated. - View Dependent Claims (89, 90, 91)
-
-
92. A solidified peelable layer for delivering a drug, comprising:
-
a) a drug;
b) a non-volatile solvent system having one or more non-volatile solvent, wherein the non-volatile solvent system provides a window of operable solubility for the drug such that the drug is deliverable at therapeutically effective rates for at least 2 hours; and
c) a peel-forming agent, wherein said peelable layer can be stretched in at least one direction by 10% without breaking or cracking. - View Dependent Claims (93, 94, 95, 96, 97, 98)
-
-
99. An adhesive peel-forming formulation for dermal delivery of a drug comprising:
-
a) a drug;
b) a peel-forming agent; and
c) a solvent vehicle, comprising i) a volatile solvent system including one or more volatile solvent, and ii) a non-volatile solvent system including one or more non-volatile solvent, wherein when said adhesive peel-forming formulation is applied to a skin surface, the adhesive peel-forming formulation forms a solidified peelable layer having a contact surface, said contact surface having a first area dimension, said solidified peelable layer being stretchable such that the first area dimension is capable of being stretched to a second area dimension that is 10% larger than the first area dimension without cracking, breaking, or separating from the skin surface; and
wherein after the formation of said solidified peelable layer and after the volatile solvent system is substantially evaporated the drug continues to be delivered at therapeutically effective rates. - View Dependent Claims (100, 101, 102, 103, 104, 105, 106, 107, 108)
-
-
109. An adhesive peel-forming formulation for dermal delivery of a drug, comprising:
-
a) a drug selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDs) including ketoprofen and diclofanec;
COX-2 selective NSAIDs and agents;
COX-3 selective NSAIDs and agents;
local anesthetics including lidocaine, bupivacaine, ropivacaine, and tetracaine;
steroids including dexamethasone;
antibiotics, retinoids, clonidine, peroxides, retinol, salicylic acid, imiquimod, humectants, emollients, antiviral drugs including acyclovir, trifluridine, idoxuridine, penciclovir, famciclovir, cidofovir, gancyclovir, valacyclovir, podofilox, podophyllotoxin,ribavirin, abacavir, delavirdine, didanosine, efavirenz, lamivudine, nevirapine, stavudine, zalcitabine, zidovudine, amprenavir, indinavir, nelfinavir, ritonavir, saquinavir, amantadine, interferon, oseltamivir, ribavirin, rimantadine, and zanamivir;
antifungal drugs including ciclopirox, imidazole, miconazole, clotrimazole, econazole, ketoconazole, oxiconazole, sulconazole and allylamine derivatives including butenafine, naftifine, and terbinafine; and
combinations thereof;
b) a solvent vehicle, comprising;
i) a volatile solvent system including one or more volatile solvent selected from the group of water, ethanol, isopropyl alcohol, ethyl acetate, acetone, mixtures thereof, and ii) a non-volatile solvent system including one or more non-volatile solvent, wherein the non-volatile solvent system has a solubility with respect to the drug that is within a window of operable solubility such that the drug is deliverable at therapeutically effective rates over a sustained period of time; and
said one or more non-volatile solvent is selected from the group consisting of glycerol, polyethylene glycol having a weight average molecular weight from about 200 MW to 800 MW, mineral oil, petrolatum, castor oil, n-methyl pyrrolidone, vegetable oil, honey, oleyl alcohol, dipropylene glycol, polyoxyethylene derivative of sorbitan esters, saturated polyglycolyzed C8 to C10 glycerides, polyoxyethylated fatty acid glycerides, dimethylsulfoxide, fatty alcohol, isopropyl myristate, ethyl oleate, essential oils including eugenol and rose oil, oleic acid, oleyl alcohol, isostearic acid, fatty acids including medium chain fatty acids, and mixtures thereof; and
c) a peel-forming agent, selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidone, carrageenin, gelatin, dextrin, guar gum, xantham gum, polyethylene oxide, hydroxyethylcellulose, ehtylcellulose, carboxymethylcellulose, hydroxypropylcellulose, copolymers of methyl vinyl ether and maleic anhydride, polyvinyl alcohol-polyethylene glycol co-polymers, methacrylic acid and methacrylate-based copolymers including poly(methacrylic acid) copolymers, methylmethacrylate copolymers, methyacrylic acid-ethyl acrylate copolymers;
wherein the formulation has a viscosity suitable for application and adhesion to a skin surface prior to evaporation of the volatile solvent system, and wherein the formulation applied to the skin surface forms a solidified peelable layer after at least partial evaporation of the volatile solvent system, wherein the drug continues to be delivered after the volatile solvent system is substantially evaporated, wherein the formulation has a drying time of 5 minutes or shorter under standard skin and ambient conditions, wherein the weight ratio of the non-volatile solvent system to the peel-forming polymer is from about 0.2;
1 to about 1.2;
1, and wherein the solidified peelable layer can be stretched in at least one direction by 10% without cracking, breaking, or separating from the skin.
-
Specification