# US 10,500,282 B2 · Supersaturated stabilized nanoparticles for poorly soluble drugs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,282 B2 - Document ID: US10500282B2 - Status: Granted - Kind: B2 - Application number: 14/653,061 - Filed: 2013-12-19 - Published: 2015-11-26 - Granted: 2019-12-10 - Earliest claimed: 2012-12-19 - Assignees: Kashiv Biosciences, LLC - Applicants: Kashiv BioSciences, LLC - Inventors: Dipen Desai; Wantanee Phuapradit; Anekant Jain; Atsawin Thongsukmak; Navnit H. Shah - Web page: https://patentgrep.com/patent/US10500282B2 ## 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 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 9/146: {with organic macromolecular compounds} - A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)} - A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50} - A61K 9/4866: {Organic macromolecular compounds} - A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose} - A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose} - A61K 9/5078: {with drug-free core} - A61K 31/421: 1,3-Oxazoles, e.g. pemoline, trimethadione - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 31/57: substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone - A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) - A61K 38/07: Tetrapeptides - A61K 2800/5424: anionic - A61K 2800/5426: cationic - 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 pharmaceutical composition and method of producing supersaturated stabilized nanoparticles of poorly soluble drugs having average sizes less than 1 μm, or less than 800 nm, or less than 500 nm, comprising at least one pharmaceutically active ingredient, a hydrophilic polymer, a water-soluble surfactant, and subsequently stabilized by ionic polymers. ## Claims ### Claim 1 A stabilized suspension suitable for oral administration and downstream processing of solid dosage forms, consisting of: a) an aqueous solution consisting of an aqueous solvent, a water-soluble surfactant, a de-agglomeration agent and a water-soluble polymer; and b) particles of a poorly soluble pharmaceutically active ingredient suspended in the aqueous solution, wherein the water-soluble surfactant is an anionic surfactant selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, docusate salt, sodium stearate, and a combination thereof, the de-agglomeration agent is an anionic polymer that is a copolymer of methacrylic acid and ethyl acrylate, and the water-soluble polymer is hydroxypropyl methylcellulose, wherein the poorly soluble pharmaceutically active ingredient has an average particle size of about 800 nm or less, wherein, apart from the water-soluble surfactant and the water-soluble polymer, no other polymer is added to the aqueous solution containing the particles of the poorly soluble pharmaceutically active ingredient before particle size reduction, and wherein the stabilized suspension provides a supersaturated concentration of the poorly soluble pharmaceutically active ingredient. ### Claim 2 (depends on 1) The stabilized suspension of claim 1, wherein the ratio of the poorly soluble pharmaceutically active ingredient to the de-agglomeration agent is between 20:1 and 1:20. ### Claim 3 (depends on 1) The stabilized suspension of claim 1, wherein the ratio of the poorly soluble pharmaceutically active ingredient to the de-agglomeration agent is between 5:1 and 1:5. ### Claim 4 (depends on 1) The stabilized suspension of claim 1, wherein the ratio of the poorly soluble pharmaceutically active ingredient to the de-agglomeration agent is between 3:1 and 1:3. ### Claim 5 (depends on 1) The stabilized suspension of claim 1, wherein the particles of the poorly soluble pharmaceutically active ingredient have an average size of about 500 nm or less. ### Claim 6 (depends on 1) The stabilized suspension of claim 1, wherein the anionic surfactant is selected from the group consisting of docusate salt and sodium lauryl sulfate. ### Claim 7 (depends on 1) A method of treating a patient comprising administering the stabilized suspension of claim 1. ### Claim 8 A dry powder consisting of: a) a water-soluble surfactant, a de-agglomeration agent, and a water-soluble polymer; and b) particles of a poorly soluble pharmaceutically active ingredient, wherein the water-soluble surfactant is an anionic surfactant selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, docusate salt, sodium stearate, and a combination thereof, the de-agglomeration agent is an anionic polymer that is a copolymer of methacrylic acid and ethyl acrylate, and the water-soluble polymer is hydroxypropyl methylcellulose, wherein the poorly soluble pharmaceutically active ingredient has an average particle size of about 800 nm or less, and wherein, apart from the water-soluble surfactant and the water-soluble polymer, no other polymer is present before particle size reduction. ### Claim 9 (depends on 8) The dry powder of claim 8, wherein the dry powder is loaded into a capsule.