# US 10,369,101 B2 · Parenteral diclofenac composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,369,101 B2 - Document ID: US10369101B2 - Status: Granted - Kind: B2 - Application number: 14/777,193 - Filed: 2014-03-17 - Published: 2016-02-11 - Granted: 2019-08-06 - Earliest claimed: 2013-03-15 - Assignees: Latitude Pharmaceuticals, Inc. - Applicants: Latitude Pharmaceuticals Inc. - Inventors: Franklin Okumu; Andrew X. Chen; Hailiang Chen - Web page: https://patentgrep.com/patent/US10369101B2 ## CPC - A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) - 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 application provides parenteral compositions of diclofenac or its pharmaceutically acceptable salt and methods for making and using such compositions. Some of the compositions of the present application has one or more following properties: (1) ready to be injectable, (2) in the form of an oil-in-water emulsion, (3) stable under appropriate storage conditions, (4) containing therapeutically effective amount of diclofenac or its pharmaceutically acceptable salt, (5) sterilizable by filtration (6) containing components acceptable by regulatory agencies (e.g. the FDA), (7) containing low oil content and thus not exacerbating hyerlipidemia, and (8) is neither hyperallergenic nor vein irritating. ## Claims ### Claim 1 A parenteral composition in the form of oil-in-water nanoemulsion that comprises: (a) 2% w/w to 5% w/w of diclofenac or a pharmaceutically acceptable salt thereof, (b) at least one oil component consisting essentially of a medium-chain triglyceride, wherein the at least one oil component is present between about 1% w/w to about 20% w/w, (c) at least one phospholipid component, wherein the at least one phospholipid component is present between about 1% w/w to about 20% w/w, (d) about 60% w/w to about 80% w/w of an aqueous phase, wherein the total concentration of the medium-chain triglyceride and the phospholipid component is in the range from about 15% w/w to about 35% w/w, wherein the nanoemulsion has percentage of fat greater than 5 microns (PFAT5) of less than 0.05% when stored at a temperature of about 2-8° C. or about 25° C. for about 12 to about 24 months, and wherein the content of the phospholipid component, the oil component and the aqueous phase within the nanoemulsion region in a ternary phase disgram consisting of a phospholipid component, an oil component and an aqueous phase, and the nanoemulsion region is defined by connecting five compositions (A, B, C, D and E) with lines (A-B; B-C; C-D; D-E, and E-A), but not including the lines, in the said ternary phase diagram and the five compositions (A, B, C, D and E), corresponding to weight ratios of the phospholipid component: the oil component: the aqueous phase of 10:0:86.25 for A, 8:2:86.25 for B, 3:32:61.25 for C, 18:17:61.25 for D and 20:0:76.25 for E. ### Claim 2 (depends on 1) The composition of claim 1, wherein the medium chain triglyceride is synthetic or derived from a natural source. ### Claim 3 (depends on 1) The composition of claim 1, wherein the phospholipid component comprises a phosphatidyl choline, a lecithin, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, or a mixture thereof. ### Claim 4 (depends on 1) The composition of claim 1, wherein the phospholipid component is a lecithin. ### Claim 5 (depends on 1) The composition of claim 1, wherein the composition has an osmolality of at least 150 mOsm (milliosmoles). ### Claim 6 (depends on 1) The composition of claim 1, wherein the composition has at least one of the following pharmacokinetic parameters: a) AUC(0-t) is at least about 900 ng/mL*h, b) AUC(0-t) with coefficient of variation (CV %) less than about 30%, c) AUC(0-inf) is at least about 900 ng/mL*h, and d) AUC(0-inf) with coefficient of variation (CV %) less than about 30%. ### Claim 7 (depends on 1) The parenteral composition of claim 1 comprising: 2% w/w to 5% w/w of diclofenac or a pharmaceutically acceptable salt thereof, about 5% w/w of medium chain triglycerides, about 10% w/w of lecithin, and about 70% w/w to about 80% w/w of the aqueous phase. ### Claim 8 (depends on 1) The parenteral composition of claim 1, wherein the mean oil droplet diameter is less than 200 nm. ### Claim 9 (depends on 1) The parenteral composition of claim 1, wherein the composition displays an additional peak at about 1360 cm−1 to about 1370 cm−1 when a sample of the composition is placed in a KBr pellet and subjected to FT-IR analysis. ### Claim 10 (depends on 1) The parenteral composition of claim 1, wherein the composition is substantially free of a thermal event when a sample of the composition is placed in a Differential Scanning calorimeter, wherein the sample is heated at the speed of 5° C./min from 30° C. to 380° C. under nitrogen gas. ### Claim 11 (depends on 1) The composition of claim 1, wherein diclofenac sodium is at a concentration between about 5 mg/mL to about 45 mg/mL. ### Claim 12 (depends on 1) The composition of claim 1, wherein diclofenac sodium is at a concentration of about 18.75 mg/mL or 37.5 mg/mL. ### Claim 13 (depends on 1) The composition of claim 1, wherein (a) diclofenac or a pharmaceutically acceptable salt thereof is present at about 3.75% w/w; (b) the medium-chain triglyceride is present at about 5% w/w; and (c) the phospholipid component is egg lecithin present at about 10% w/w.