# US 11,992,553 B2 · Inhalable powder formulations of alginate oligomers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,553 B2 - Document ID: US11992553B2 - Status: Granted - Kind: B2 - Application number: 17/445,577 - Filed: 2021-08-20 - Published: 2021-12-16 - Granted: 2024-05-28 - Earliest claimed: 2021-08-20 - Assignees: Algipharma AS - Applicants: AlgiPharma AS - Inventors: Bildad Nyambura; Anand Bakle; Arne Dessen - Web page: https://patentgrep.com/patent/US11992553B2 ## CPC - A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles} - A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]} - A61K 9/1617: {Organic compounds, e.g. phospholipids, fats} - A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules} - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/1682: {Processes} - A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)} - A61P 11/00: Drugs for disorders of the respiratory system - 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 ## Abstract A method of preparing spray dried particles for inhalation comprising providing: (i) an aqueous liquid composition including the alginate oligomer and an aqueous liquid composition including an anti-adherent compound, or (ii) an aqueous liquid composition including the alginate oligomer and an anti-adherent compound; providing an organic liquid composition including a phospholipid; combining a volume of the organic liquid composition with a volume of the aqueous liquid composition, wherein the total volume of the organic liquid composition is smaller than the total volume of the aqueous liquid composition with which it is combined, and wherein the total volume of aqueous liquid composition and said total volume of organic liquid composition are sufficient to provide a combination; homogenizing the combination to form an organic-in-aqueous liquid emulsion for spray drying; and spray drying the organic-in-aqueous liquid emulsion to form the spray dried particles for inhalation. ## Claims ### Claim 1 A method for the preparation of spray dried particles for inhalation, the spray dried particles for inhalation consisting of: at least about 70% w/w of an alginate oligomer, (ii) at least about 10% w/w in total of a phospholipid and an anti-adherent compound, wherein said phospholipid is solid at room temperature, and wherein said phospholipid is present at no less than 0.5% w/w and said anti-adherent compound is present at no less than 0.5% w/w, and (iii) no greater than about 10% w/w of further excipients, wherein said method for the preparation of said spray dried particles for inhalation comprises: (a) providing: (i) an aqueous liquid composition comprising the alginate oligomer and optionally one or more of the further excipients, and an aqueous liquid composition comprising the anti-adherent compound and optionally one or more of the further excipients, or (ii) an aqueous liquid composition comprising the alginate oligomer and the anti-adherent compound, and optionally one or more of the further excipients, (b) providing an organic liquid composition comprising the phospholipid, and optionally one or more of the further excipients, (c) combining a volume of the organic liquid composition with a volume of the aqueous liquid compositions of (ai), or the aqueous liquid composition of (aii), and optionally a volume of further aqueous or organic liquid compositions comprising one or more of the further excipients, wherein the total volume of the organic liquid compositions is smaller than the total volume of the aqueous liquid compositions with which it is combined, and wherein said total volume of aqueous liquid compositions and said total volume of organic liquid compositions are sufficient to provide a combination that upon being homogenized and then spray dried would form said spray dried particles for inhalation, (d) homogenizing the combination so formed at any time during step (c) or on upon completion of step (c) to form an organic-in-aqueous liquid emulsion for spray drying, and (e) spray drying the organic-in-aqueous liquid emulsion formed in step (d) to form said spray dried particles for inhalation. ### Claim 2 (depends on 1) The method of claim 1, wherein the organic liquid composition comprising the phospholipid is a solution of the phospholipid in an organic solvent selected from a group consisting of alcohols, ketones, acetates, halogenated solvents, aliphatic solvents and a combination thereof. ### Claim 3 (depends on 2) The method of claim 2, wherein the organic solvent is selected from the group consisting of methanol, ethanol, C3 alcohols, C4 alcohols, acetone, ethyl acetate, dichloromethane, chloroform, heptane, hexane, pentane and a combination thereof. ### Claim 4 (depends on 1) The method of claim 1, where the total volume of organic liquid compositions and the total volume of aqueous liquid compositions have a ratio of 20-40:60-80. ### Claim 5 (depends on 4) The method of claim 4, where the ratio of the total volume of organic liquid compositions to the total volume of aqueous liquid compositions is about 25:75. ### Claim 6 (depends on 1) The method of claim 1, wherein step (d) comprises mechanical and/or ultrasonic homogenization of the combination of the aqueous liquid compositions and organic liquid compositions. ### Claim 7 (depends on 1) The method of claim 1, wherein the organic-in-aqueous liquid emulsion is a substantially stable emulsion that will persist for at least 10 min following cessation of homogenization. ### Claim 8 (depends on 1) The method of claim 1, wherein said particles contain at least about 75% w/w of the alginate oligomer. ### Claim 9 (depends on 1) The method of claim 1, wherein said particles contain at least about 15% w/w in total of the phospholipid and the anti-adherent compound. ### Claim 10 (depends on 1) The method of claim 1, wherein said particles contain no less than 3% w/w of the phospholipid. ### Claim 11 (depends on 1) The method of claim 1, wherein said particles contain no less than 10% w/w of the anti-adherent compound. ### Claim 12 (depends on 1) The method of claim 1, wherein the relative amounts of phospholipid and anti-adherent compound present in the particles are in a ratio of 1:3. ### Claim 13 (depends on 1) The method of claim 1, wherein the relative amounts of the alginate oligomer, the phospholipid and anti-adherent compound present in the particles are in a ratio of 8:0.5:1.5. ### Claim 14 (depends on 1) The method of claim 1, wherein said particles contain essentially no further excipients. ### Claim 15 (depends on 1) The method of claim 1, wherein said particles consist of about 80% w/w of the alginate oligomer, about 15% of the w/w anti-adherent compound, and about 5% w/w of the phospholipid. ### Claim 16 (depends on 1) The method of claim 1, wherein said particles have a geometric particle size distribution in which d50 is <5 μm and d90 is <10 μm. ### Claim 17 (depends on 16) The method of claim 16 wherein the particles have a geometric particle size distribution in which d10 is <1.5 μm. ### Claim 18 (depends on 1) The method of claim 1, wherein said particles have a FPM<4.46 μm of greater than about 10 mg per 40 mg of particles. ### Claim 19 (depends on 1) The method of claim 1, wherein said particles have an emitted dose of greater than about 65%. ### Claim 20 (depends on 1) The method of claim 1, wherein the alginate oligomer has a degree of polymerization (DP), or a number average degree of polymerization (DPn) of 4 to 100. ### Claim 21 (depends on 1) The method of claim 1, wherein the alginate oligomer has at least 70% G residues. ### Claim 22 (depends on 1) The method of claim 1, wherein the alginate oligomer has a number average degree of polymerization in the range 5 to 20, a guluronate fraction (FG) of at least 0.85 and a mannuronate fraction (FM) of no more than 0.15. ### Claim 23 (depends on 1) The method of claim 1, wherein the alginate oligomer has at least 70% M residues. ### Claim 24 (depends on 1) The method of claim 1, wherein the phospholipid is selected from the group consisting of phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phosphatidylserines, phosphatidylinositols and a combination thereof. ### Claim 25 (depends on 1) The method of claim 1, wherein the phospholipid is selected from the group consisting of saturated phosphatidyl choline, unsaturated phosphatidyl choline, phosphatidyl ethanol amine, phosphatidyl glycerol, phosphatidyl serine, phosphatidyl inositol, dioleoylphosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoylphosphatidylcholine (DPPC; 1, 2-Dipalmitoyl-snglycero-3-phosphocholine), distearoyl phosphatidylcholine, 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), diarachidoyl phosphatidylcholine, dibenoyl phosphatidylcholine, ditricosanoyl phosphatidylcholine, dilignoceroylphatidylcholine, dimiristoylphosphatidylethanolamine, dipalmitoyl-phosphatidylethanoalamine, pipalmitoleoylphosphatidylethanolamine, distearoyl-phosphatidyl ethanolamine, dimyristoylphosphatidylglycerol, dipalmitoylphosphatidyl glycerol, dipalmitolcoylphosphatidylglycerol and hydrogenated derivatives, and a combination thereof. ### Claim 26 (depends on 1) The method of claim 1, wherein the anti-adherent compound is selected from the group consisting of an amino acid, a monosaccharide, a disaccharide and a combination thereof. ### Claim 27 (depends on 26) The method of claim 26 wherein the amino acid is selected from the group consisting of leucine, isoleucine, alanine, valine, phenylalanine, lysine, glycine, and a combination thereof. ### Claim 28 (depends on 1) The method of claim 1, wherein said particles consist of (i) about 80% w/w of an alginate oligomer, wherein said alginate oligomer has a number average degree of polymerization in the range 5 to 20, a guluronate fraction (FG) of at least 0.85 and a mannuronate fraction (FM) of no more than 0.15, (ii) about 5% w/w of DPPC, and (iii) about 15% w/w glycine. ### Claim 29 A method for the preparation of an organic-in-aqueous liquid emulsion for spray drying so as to form spray dried particles for inhalation, the spray dried particles for inhalation consisting of (i) at least about 70% w/w of an alginate oligomer, (ii) at least about 10% w/w in total of a phospholipid and an anti-adherent compound, wherein said phospholipid is solid at room temperature, and wherein said phospholipid is present at no less than 0.5% w/w and said anti-adherent compound is present at no less than 0.5% w/w, and (iii) no greater than about 10% w/w of further excipients, wherein said method for the preparation of said spray dried particles for inhalation comprises: (a) providing: (ai) an aqueous liquid composition comprising the alginate oligomer and optionally one or more of the further excipients, and an aqueous liquid composition comprising the anti-adherent compound and optionally one or more of the further excipients, or (aii) an aqueous liquid composition comprising the alginate oligomer and the anti-adherent compound, and optionally one or more of the further excipients, (b) providing an organic liquid composition comprising the phospholipid, and optionally one or more of the further excipients, (c) combining a volume of the organic liquid composition with a volume of the aqueous liquid compositions of (ai), or the aqueous liquid composition of (aii), and optionally a volume of further aqueous or organic liquid compositions comprising one or more of the further excipients, wherein the total volume of the organic liquid compositions is smaller than the total volume of the aqueous liquid compositions with which it is combined, and wherein said total volume of aqueous liquid compositions and said total volume of organic liquid compositions are sufficient to provide a combination that upon being homogenized and then spray dried would form said spray dried particles for inhalation, and (d) homogenizing the combination so formed at any time during step (c) or on upon completion of step (c) to form the organic-in-aqueous liquid emulsion for spray drying.