# US 11,026,908 B2 · Extended release dosage forms of pregabalin > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,908 B2 - Document ID: US11026908B2 - Status: Granted - Kind: B2 - Application number: 16/318,308 - Filed: 2017-07-16 - Published: 2019-10-03 - Granted: 2021-06-08 - Earliest claimed: 2016-07-17 - Assignees: Mapi Pharma Ltd. - Applicants: Mapi Pharma Ltd. - Inventors: Yoram Sela; Shai Rubnov - Web page: https://patentgrep.com/patent/US11026908B2 ## CPC - A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205) - A61K 9/2009: {Inorganic compounds} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)} - A61K 9/2846: {Poly(meth)acrylates} - A61K 9/485: {Inorganic compounds} - A61K 9/4858: {Organic compounds} - A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose} - A61K 9/5078: {with drug-free core} - A61K 9/5084: {Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077)} - 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 The present invention relates to extended-release pharmaceutical compositions comprising pregabalin or a salt thereof, which are adapted to release the pregabalin active ingredient according to a dual release profile. The formulations comprise two components, the first (fast ER) providing extended-release of the active ingredient in a short controlled manner lasting from about 4 to about 6 hours, and the second (slow ER or maintenance) providing extended release of the active ingredient over a period of 24 hours. The proportion of each component in the formulation may be adjusted to achieve the desired AUC and therapeutic effect following oral administration to a subject. The invention further relates to methods of using the pharmaceutical compositions for treating conditions and disorders which are responsive to pregabalin treatment, such as neuropathic pain associated with diabetic peripheral neuropathy (DPN), post herpetic neuralgia (PHN), epilepsy, seizures and fibromyalgia. ## Claims ### Claim 1 An oral, extended-release (ER) pharmaceutical composition comprising as an active ingredient pregabalin or a salt thereof and a pharmaceutically acceptable carrier or excipient, wherein the composition comprises a first component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 4 to about 6 hours, and a second component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 24 hours, wherein the first component and the second component are each in the form of ER beads or mini-tablets that are filled into hard or soft gelatin capsules or compressed into dispersible tablets, wherein the mini-tablets or ER beads of the first component are uncoated, and wherein the mini-tablets or ER beads of the second component are coated. ### Claim 2 (depends on 1) The composition of claim 1, wherein the first component and the second component are each in the form of ER beads or mini-tablets comprising pregabalin, a first pH-independent release controlling polymer and at least one lubricant and/or matrix former, wherein the first component is uncoated and wherein the second component further comprises a coating comprising a second pH-independent release controlling polymer which may be the same or different from the first release controlling polymer. ### Claim 3 (depends on 2) The composition of claim 2, wherein the first component and the second component are each in the form of ER beads or mini-tablets comprising pregabalin, ethyl cellulose, glyceryl behenate and magnesium stearate, wherein the first component is uncoated and wherein the second component further comprises a coating comprising ethyl cellulose. ### Claim 4 An oral, extended-release (ER) pharmaceutical composition comprising as an active ingredient pregabalin or a salt thereof and a pharmaceutically acceptable carrier or excipient, wherein the composition comprises a first component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 4 to about 6 hours, and a second component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 24 hours, wherein the first component and the second component are each in the form of ER beads or mini-tablets that are filled into hard or soft gelatin capsules or compressed into dispersible tablets, wherein the mini-tablets or ER beads of the first and the second component are each coated, wherein the same coating in different amounts, is used for the first and second components. ### Claim 5 An oral, extended-release (ER) pharmaceutical composition comprising as an active ingredient pregabalin or a salt thereof and a pharmaceutically acceptable carrier or excipient, wherein the composition comprises a first component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 4 to about 6 hours, and a second component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 24 hours, wherein the composition comprises a total of from about 50 mg to about 600 mg of pregabalin or a salt thereof, and wherein said total amount is divided between the first and second components of the composition. ### Claim 6 An oral, extended-release (ER) pharmaceutical composition comprising as an active ingredient pregabalin or a salt thereof and a pharmaceutically acceptable carrier or excipient, wherein the composition comprises a first component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 4 to about 6 hours, and a second component that provides pH independent controlled release of the pregabalin active ingredient over a time period of about 24 hours, wherein the composition is in the form of ER beads, mini-tablets, double-layer tablets, hard or soft gelatin capsule, a pellet, or combinations thereof. ### Claim 7 (depends on 6) The composition of claim 6, wherein the first component and the second component are each in the form of ER beads or mini-tablets that are filled into hard or soft gelatin capsules or compressed into dispersible tablets. ### Claim 8 (depends on 7) The composition of claim 7, wherein the first component and the second component are each in the form of ER beads or mini-tablets comprising pregabalin, a first pH-independent release controlling polymer, at least one lubricant and/or matrix former, and a coating comprising a second pH-independent release controlling polymer which may be the same or different from the first release controlling polymer. ### Claim 9 (depends on 6) The composition of claim 6, wherein the first component and the second component are each in the form of ER beads, wherein the ER beads are prepared by coating or layering over sugar spheres, or by extrusion and spheronization. ### Claim 10 (depends on 6) The composition of claim 6, wherein the first component and the second component are each in the form of mini-tablets or double-layer tablets which are prepared by granulation or direct compression.