# US 5,702,721 A · Transdermal therapeutic system exhibiting an increased active substance flow and process for the production thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,702,721 A - Document ID: US5702721A - Status: Granted - Kind: A - Application number: 08/298,236 - Filed: 1994-08-30 - Granted: 1997-12-30 - Earliest claimed: 1989-04-01 - Assignees: LTS Lohmann Therapie-Systeme AG - Inventors: Michael Horstmann; Fritz Herrmann - Web page: https://patentgrep.com/patent/US5702721A ## CPC - A61K 9/703: {characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches} - 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: 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) ## Abstract A transdermal therapeutic system exhibiting layered structure consists of a backing layer which is impermeable to active substances, a matrix having water-insoluble basic material and islands (inclusions) divided therein, and a layer controlling the access of cutaneous liquid by means of which the matrix is activatable. Process for the production are described. ## Claims ### Claim 1 A process for the production of a transdermal therapeutic system exhibiting a layered structure, consisting of a backing layer (11) which is substantially impermeable to active substances, a matrix (12) comprising the active substance, and a layer (13) controlling the access of cutaneous liquid, in which the matrix (12) consists of a material (15) which is permeable to water vapour, but substantially water-insoluble and free of active substances, in which islands (14) are distributed which consist of a solid solution of pharmaceutical in a water-soluble or water-swellable base material, the proportion of islands being between 0.5 and 70%, the matrix being activatable by cutaneous liquid, the step which comprises spray drying a solution of the active substance and the water soluble or water-swellable base material in a suitable volatile solvent. ### Claim 2 (depends on 1) A process for the production of a transdermal therapeutic system as defined in claim 1, characterized in that the matrix (12, 22) or the layer controlling the access of cutaneous liquid (13, 23) are applied to a carrier, which has been rendered non-adhesive, in a solution or suspension in a suitable solvent, and that the solvent is subsequently removed by drying. ### Claim 3 (depends on 1) A process for the production of a transdermal therapeutic system as defined in claim 1, characterized in that the matrix (12, 22) or the cutaneous liquid access controlling layer (13, 23) is liquefied by application of heat, and applied in this state to a non-adhesive carrier. ### Claim 4 (depends on 1) A process for the production of a transdermal therapeutic system as defined in claim 1, characterized in that the matrix (12, 22) or the cutaneous liquid access controlling layer (13, 23) and backing layer (11, 21) are continuously combined by application of pressure and/or temperature. ### Claim 5 (depends on 1) A process for the production of a transdermal therapeutic system as defined in claim 1, characterized in that the matrix (22) is formed by separate manufacture of two identical layers of base material (25), optionally having a different layer thickness, sprinkling the islands (24) on one of the two layers, and subsequent application of the second layer of base material (25) under application of pressure and/or temperature. ### Claim 6 (depends on 1) A process as defined in claim 1, wherein spray-drying is effected to yield a particle size of at most 20 .mu.m. ### Claim 7 (depends on 1) A process as defined in claim 1, wherein spray-drying is effected to yield a particle size of at most 5 .mu.m. ### Claim 8 (depends on 1) A process as defined in claim 1, wherein the proportion of islands (14) to the mass of the matrix layer (12) is between 5 and 40% and spray-drying is effected to yield a particle size of at most 5 .mu.m. ### Claim 9 In a process for the production of a transdermal therapeutic system exhibiting a layered structure, consisting of a backing layer (11) which is substantially impermeable to active substances, a matrix (12) comprising the active substance, and a layer (13) controlling the access of cutaneous liquid, in which the matrix (12) consists of a material (15) which is permeable to water vapour, but substantially water-insoluble and free of active substances, in which islands (14) are distributed which consist of a solid solution of pharmaceutical in a water-soluble or water-swellable base material, the proportion of islands being between 0.5 and 70%, the matrix being activatable by cutaneous liquid, the step which comprises forming the islands (14, 24) by precipitation from a solution of the active substance and the water-soluble or water-swellable base material by means of a suitable precipitation agent in which the water-soluble or water-swellable base material is substantially insoluble. ### Claim 10 (depends on 9) A process for the production of a transdermal therapeutic system as defined in claim 9, wherein the matrix (12, 22) or the layer controlling the access of cutaneous liquid (13, 23) are applied to a carrier, which has been rendered non-adhesive, in a solution or suspension in a suitable solvent, and that the solvent is subsequently removed by drying. ### Claim 11 (depends on 9) A process for the production of a transdermal therapeutic system as defined in claim 9, wherein the matrix (12, 22) or the cutaneous liquid access controlling layer (13, 23) is liquefied by application of heat, and applied in this state to a non-adhesive carrier. ### Claim 12 (depends on 9) A process for the production of a transdermal therapeutic system as defined in claim 9, wherein the matrix (12, 22), the cutaneous liquid access controlling layer (13, 23) and backing layer (11, 21) are continuously combined by application of pressure or temperature or both. ### Claim 13 (depends on 9) A process for the production of a transdermal therapeutic system as defined in claim 9, wherein the matrix (22) is formed by separate manufacture of two identical layers of base material (25), sprinkling the islands (24) on one of the two layers, and subsequent application of the second layer of base material (25) under application of pressure or temperature or both. ### Claim 14 In a process for the production of a transdermal therapeutic system exhibiting a layered structure, consisting of a backing layer (11) which is substantially impermeable to active substances, a matrix (12) comprising the active substance and a layer (13) controlling the access of cutaneous liquid, in which the matrix (12) consists of a material (15) which is permeable to water vapour, but substantially water-insoluble and free of active substances in which islands (14) are distributed which consists of a solid solution of pharmaceutical in a water-soluble or water-swellable base material the proportion of islands being between 0.5 and 70%, the matrix being activatable by cutaneous liquid which comprises loading the islands (14, 24) with active substance by means of solid-liquid absorption in a suspension of unloaded islands in a suitable volatile solvent comprising the active substance in dissolved form. ### Claim 15 (depends on 14) A process for the production of a transdermal therapeutic system as defined in claim 14, wherein the matrix (12, 22) or the layer controlling the access of cutaneous liquid (13, 23) are applied to a carrier, which has been rendered non-adhesive, in a solution or suspension in a suitable solvent, and that the solvent is subsequently removed by drying. ### Claim 16 (depends on 14) A process for the production of a transdermal therapeutic system as defined in claim 14, wherein the matrix (12, 22) or the cutaneous liquid access controlling layer (13, 23) is liquefied by application of heat, and applied in this state to a non-adhesive carrier. ### Claim 17 (depends on 14) A process for the production of a transdermal therapeutic system as defined in claim 14, wherein the matrix (12, 22) or the cutaneous liquid access controlling layer (13, 23) and backing layer (11, 21) are continuously combined by application of pressure or temperature or both. ### Claim 18 (depends on 14) A process for the production of a transdermal therapeutic system as defined in claim 14, wherein the matrix (22) is formed by separate manufacture of two identical layers of base material (25), sprinkling the islands (24) on one of the two layers, and subsequent application of the second layer of base material (25) under application of pressure or temperature or both. ### Claim 19 (depends on 15) A process for the production of a transdermal therapeutic system as defined in claim 15, wherein the carrier is a foil. ### Claim 20 In a process for the production of a transdermal therapeutic system exhibiting a layered structure comprising a backing layer (11) which is substantially impermeable to active substances, a matrix layer (12) containing the active substance in an activatable form, and a layer (13) controlling the access of cutaneous liquid, wherein said matrix layer (12) comprises a material (15) which is permeable to water vapour, but substantially water-insoluble and free of active substances, in which islands (14) are distributed which consist of a solid solution of pharmaceutical in a water-soluble or water-swellable base material, the proportion of said islands (14) to the mass of said matrix layer (12) lying between 0.5 to 70% said matrix layer being activatable by cutaneous liquid, the step which comprises spray drying a solution of the active substance and the water-soluble and water-swellable base material in a suitable volatile solvent and effecting the spray-drying to yield a particle size of at most 20 .mu.m. ### Claim 21 (depends on 20) A process as defined in claim 20, wherein the proportion of islands (14) to the mass of the matrix layer (12) is between 5 and 40%.