# US 8,784,880 B2 · Titratable dosage transdermal delivery system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,784,880 B2 - Document ID: US8784880B2 - Status: Granted - Kind: B2 - Application number: 12/894,512 - Filed: 2010-09-30 - Published: 2011-01-27 - Granted: 2014-07-22 - Earliest claimed: 2000-11-16 - Assignees: Purdue Pharma L.P. - Applicants: Curtis Wright, IV - Inventors: Curtis Wright, IV - Web page: https://patentgrep.com/patent/US8784880B2 ## CPC - A61K 9/7084: {Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches} - A61K 9/703: {characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches} - A61K 9/7038: {Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer} - A61K 9/7092: {Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs} - A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl - A61K 31/485: Morphinan derivatives, e.g. morphine, codeine - A61P 3/02: Nutrients, e.g. vitamins, minerals - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/00: Drugs for disorders of the endocrine system - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 23/00: Anaesthetics - A61P 23/02: Local anaesthetics - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 25/08: Antiepileptics; Anticonvulsants - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/04: Antibacterial agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61F 2013/0296: {for making transdermal patches (chemical processes excluded)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) ## Abstract The present invention relates to a titratable dosage transdermal delivery system for systemic delivery of a therapeutic agent or drug. The system comprises a plurality of patch units that are connected along one or more borders. The plurality of patch units are divisible into units along the one or more borders having one or more lines of separation. Each patch unit is surrounded by a border. The therapeutic patch has at least a backing layer and a therapeutic agent comprising layer. The dosage of therapeutic agent delivered to a patient is proportional to the number of patch unit applied per treatment. The system enables systemic administration of a titratable dosage of therapeutic agent, adjustable by the patient under the direction of a physician, through the skin or mucosa. Moreover, the invention relates to a method of making the titratable dosage transdermal delivery system. Furthermore, the invention relates to a method of providing a titratable amount of therapeutic agent to a patient using the transdermal delivery system of the invention. ## Claims ### Claim 1 A method of delivering a drug through a patient's skin comprising: a. providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising a drug disposed on the backing layer, and an adhesive layer, wherein the drug layer is a drug-in-adhesive layer, the drug is a narcotic analgesic, a local anesthetic, a sedative, a tranquilizer, or a combination thereof, the borders of the backing layer are free of the drug, at least a portion of the adhesive layer is disposed on the borders of the backing layer; the plurality of patch units are connected to each other along one or more borders of the patch units; and each patch unit is defined by one or more lines of separation along the borders of the patch units; b. separating at least one patch unit from the transdermal delivery system along at least one line of separation; and c. applying at least one patch unit such that the drug layer makes contact with the skin. ### Claim 2 (depends on 1) The method of claim 1 wherein the patch units are applied on the skin of the plantar foot arch, lateral ankle, palm, upper arm, ventral forearm, dorsal forearm, back, chest, thigh, abdomen, scalp, axilla, forehead, lower back, chest, buttocks or scrotum. ### Claim 3 (depends on 1) The method of claim 1 wherein a portion of the adhesive layer is disposed on the drug layer; and a cover layer is disposed on the adhesive layer. ### Claim 4 (depends on 1) The method of claim 1 wherein the drug is fentanyl, etorphine, buprenorphine, penzocaine, morphine, morphine derivative, lidocaine, prilocaine, mepivacaine, pentabarbital sodium, phenobarbital, secobarbital sodium, codeine, (a-bromoisovaleryl) urea, carbromal, sodium phenobarbital, or a combination thereof. ### Claim 5 (depends on 1) The method of claim 1 wherein said transdermal delivery system further comprises a release limiting layer disposed on the drug layer. ### Claim 6 (depends on 1) The method of claim 1 wherein the drug is encapsulated by microcapsules. ### Claim 7 (depends on 1) The method of claim 1 wherein the drug layer comprises about 0.1-90% by weight of the drug. ### Claim 8 (depends on 1) The method of claim 1 wherein the drug layer comprises about 10-45% by weight of the drug. ### Claim 9 (depends on 1) The method of claim 1 wherein the drug layer comprises about 25-40% by weight of the drug. ### Claim 10 (depends on 1) The method of claim 1 wherein the drug layer further comprises a softening agent, wherein the softening agent is dodecanol, undecanol, octoanol esters of carboxylic acids, or a combination thereof. ### Claim 11 (depends on 1) The method of claim 1 wherein the drug layer further comprises a permeation enhancing agent. ### Claim 12 (depends on 3) The method of claim 3 wherein the cover layer comprises a notch so as to facilitate separation of the cover layer from the adhesive layer. ### Claim 13 (depends on 1) The method of claim 1 wherein the transdermal delivery system is stored in a resealable pouch. ### Claim 14 (depends on 1) The method of claim 1 wherein the lines of separation are parallel and/or perpendicular to each other. ### Claim 15 (depends on 1) The method of claim 1 wherein the lines of separation are lines of perforations. ### Claim 16 (depends on 1) The method of claim 1 wherein the lines of separation are spaced at regular intervals. ### Claim 17 (depends on 1) The method of claim 1 wherein the lines of separation are about 1 cm to 6 cm apart. ### Claim 18 (depends on 1) The method of claim 1 wherein 2 to 5 patch units are connected in series in the transdermal delivery system. ### Claim 19 (depends on 1) The method of claim 1 wherein 4 patch units are arranged in 2 rows and 2 columns in the transdermal delivery system. ### Claim 20 (depends on 1) The method of claim 1 wherein two to five patch units are applied on the skin. ### Claim 21 A method of delivering a drug through a patient's skin comprising: a. providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising buprenorphine disposed on the backing layer, and an adhesive layer, wherein the drug layer is a drug-in-adhesive layer, the borders of the backing layer are free of the buprenorphine, at least a portion of the adhesive layer is disposed on the borders of the backing layer; the plurality of patch units are connected to each other along one or more borders of the patch units; and each patch unit is defined by one or more lines of separation along the borders of the patch units; b. separating at least one patch unit from the transdermal delivery system along at least one line of separation; and c. applying at least one patch unit such that the drug layer makes contact with the skin. ### Claim 22 A method of delivering a narcotic analgesic through a patient's skin comprising: a. providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising a narcotic analgesic disposed on the backing layer, and an adhesive layer, wherein the drug layer is a drug-in-adhesive layer, the borders of the backing layer are free of the narcotic analgesic; at least a portion of the adhesive layer is disposed on the borders of the backing layer; the plurality of patch units are connected to each other along one or more borders of the patch units; and each patch unit s defined by one or more lines of separation along the borders of the patch units; b. separating at least one patch unit from the transdermal delivery system along at least one line of separation; and c. applying at least one patch unit such that the drug layer makes contact with the skin. ### Claim 23 (depends on 22) The method of claim 22 wherein the narcotic analgesic is fentanyl. ### Claim 24 (depends on 22) The method of claim 22 wherein the narcotic analgesic is buprenorphine. ### Claim 25 A method of adjusting the therapeutic dosage of drug delivered through a patient's skin, the method comprising: a. providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising a drug disposed on the backing layer, and an adhesive layer, wherein the drug layer is a drug-in-adhesive layer, the borders of the backing layer are free of the drug-layer; the drug is a narcotic analgesic, a local anesthetic, a sedative, a tranquilizer, or a combination thereof, at least a portion of the adhesive layer is disposed on the borders of the backing layer; the patch units are connected to each other along one or more borders of the patch units; and each patch unit is defined by one or more lines of separation along the borders of the patch units; b. separating a first number of patch units from the transdermal delivery system along at least one line of separation; c. applying the first number of patch units such that the drug layer makes contact with the skin; d. thereafter, separating a second number of patch units from the delivery system along at least one line of separation, the second number of patch units being different than or the same as the first number of patch units; and e. applying the second number of patch units such that the drug layer makes contact with the skin. ### Claim 26 (depends on 25) The method of claim 25 wherein one or more patch units from the first number of patch units are removed from the skin before applying the second number of patch units to the skin. ### Claim 27 (depends on 25) The method of claim 25 wherein one or more patch units from the first number of patch units remain on the skin before applying the second number of patch units to the skin. ### Claim 28 (depends on 25) The method of claim 25 wherein the drug is fentanyl, etorphine, buprenorphine, penzocaine, morphine, morphine derivative, lidocaine, prilocaine, mepivacaine, pentabarbital sodium, phenobarbital, secobarbital sodium, codeine, (a-bromoisovaleryl) urea, carbromal, sodium phenobarbital, or a combination thereof. ### Claim 29 (depends on 25) The method of claim 25, comprising increasing the dosage of drug through the patient's skin, wherein the second number of patch units is greater than the first number of patch units. ### Claim 30 (depends on 25) The method of claim 25, comprising decreasing the dosage of drug through the patient's skin, wherein the second number of patch units is less than the first number of patch units. ### Claim 31 A method of adjusting the therapeutic dosage of drug delivered through a patient's skin, the method comprising: a. providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising buprenorphine disposed on the backing layer, and an adhesive layer, wherein the drug layer is a drug-in-adhesive layer, the borders of the backing layer are free of the buprenorphine; at least a portion of the adhesive layer is disposed on the borders of the backing layer; the patch units are connected to each other along one or more borders of the patch units; and each patch unit is defined by one or more lines of separation along the borders of the patch units; b. separating a first number of patch units from the transdermal delivery system along at least one line of separation; c. applying the first number of patch units such that the drug layer makes contact with the skin: d. thereafter, separating a second number of patch units from the delivery system along at least one line of separation, the second number of patch units being different than or the same as the first number of patch units; and e. applying the second number of patch units such that the drug layer makes contact with the skin. ### Claim 32 (depends on 31) The method of claim 31 wherein one or more patch units from the first number of patch units are removed from the skin before applying the second number of patch units to the skin. ### Claim 33 (depends on 31) The method of claim 31 wherein one or more patch units from the first number of patch units remain on the skin before applying the second number of patch units to the skin. ### Claim 34 (depends on 31) The method of claim 31, comprising increasing the dosage of buprenorphine through the patient's skin, wherein the second number of patch units is greater than the first number of patch units. ### Claim 35 (depends on 31) The method of claim 31, comprising decreasing the dosage of buprenorphine through the patient's skin, wherein the second number of patch units is less than the first number of patch units. ### Claim 36 (depends on 1) The method of claim 1, wherein the patch unit further comprises an impermeable layer between the backing layer and the drug layer. ### Claim 37 (depends on 21) The method of claim 21, wherein the patch unit further comprises an impermeable layer between the backing layer and the drug layer.