# US 2014/0193493 A1 · Solid Dosage Forms of Oleyl Phosphocholine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193493 A1 - Document ID: US20140193493A1 - Status: Published application - Kind: A1 - Application number: 13/988,601 - Filed: 2011-11-21 - Published: 2014-07-10 - Earliest claimed: 2010-11-22 - Assignees: Dafra Pharma Research & Development Bvba - Inventors: Frans Herwig Jansen - Web page: https://patentgrep.com/patent/US20140193493A1 ## CPC - A61K 31/685: one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2095: {Tabletting processes} - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - 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 - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present invention relates to solid dosage forms of oleyl phosphocholine (C18:1-PC), or OlPC, for oral administration. Further, the present invention relates to methods for the preparation of the present solid dosage forms and the use thereof as a medicament and especially a medicament for treatment of parasitic diseases, such as leishmaniasis, chagas and malaria, and cancer both in humans and animals. Specifically, the present invention relates to a solid dosage form comprising: 6 to 25 weight % of the solid dosage form oleyl phosphocholine; 20 to 35 weight % of the solid dosage form lactose; 35 to 50 weight % of the solid dosage form cellulose; 5 to 20 weight % of the solid dosage form croscarmellose; 1 to 10 weight % of the solid dosage form hydroxypropylmethyl cellulose; and 0.05 to 1 weight % of the solid dosage form of a lubricant. ## Claims ### Claim 1 Solid dosage form of oleyl phosphocholine for oral administration comprising: 6 to 25 weight % of the solid dosage form oleyl phosphocholine; 75 to 94 weight % of the solid dosage form of one or more pharmaceutically acceptable fillers, disintegrants, binders, lubricants and/or diluents; said solid dosage form provides a friability of less than 1 weight %, preferably less than 0.5 weight %, of the solid dosage form as determined in accordance with the European Pharmacopoeia 2.9.7 standard friability test and/or said solid dosage form provides a disintegration of less than 15 minutes, preferably less than 10 minutes, as determined in accordance with the European Pharmacopoeia 2.9.1 standard disintegration test. ### Claim 2 (depends on 1) Solid dosage form according to claim 1, wherein said solid dosage form provides at least 85 weight % oleylphosphocholine release within 30 minutes as determined in accordance with the European Pharmacopoeia 2.9.3 standard dissolution test. ### Claim 3 (depends on 1) Solid dosage form according to claim 1 comprising one or more diluents or fillers selected from the group consisting of calcium carbonate, calcium phosphate (dibasic), calcium phosphate (tribasic), calcium sulphate, cellulose, microcrystalline cellulose, microcrystalline silicified cellulose, powdered cellulose, dextrates, dextrose, fructose, lactitol, lactose monohydrate, magnesium carbonate, maltitol, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, pregelatinized starch, sucrose, compressible sugar, sugar spheres, talc, xylitol and combinations thereof. ### Claim 4 (depends on 1) Solid dosage form according to claim 1 comprising one or more binders selected from the group consisting of water, acacia mucilage, alginic acid, carbomer, carboxymethylcellulose calcium, carboxymethycellulose sodium, microcrystalline cellulose, powdered cellulose, ethyl cellulose, gelatine, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, magnesium aluminum silicate, maltodextrin, methylcellulose, polydextrose, polyethylene oxide, povidone, copovidone, sodium alginate, starch paste, pregelatinized starch, Sucrose (syrup) and combinations thereof. ### Claim 5 (depends on 1) Solid dosage form according to claim 1 comprising one or more lubricants selected from the group consisting of calcium stearate, fumaric acid, glyceryl behenate, glyceryl palmitostearate, hydrogenated vegetable oil, magnesium lauryl sulphate, magnesium stearate, polyethylene glycol 4000 or 6000, sodium lauryl sulphate, sodium stearyl fumarate, starch, stearic acid, talc, zinc stearate and combinations thereof. ### Claim 6 (depends on 1) Solid dosage form according to claim 1 comprising one or more disintegrants selected from the group consisting of starch, microcrystalline cellulose, alginic acid, methyl cellulose, sodium starch glycolate, croscarmellose sodium, crospovidone, calcium silicate and combinations thereof. ### Claim 7 (depends on 1) Solid dosage form according to claim 1 comprising: 6 to 25 weight % of the solid dosage form oleyl phosphocholine; 20 to 35 weight % of the solid dosage form of one or more diluents or fillers preferably selected from the group consisting of calcium carbonate, calcium phosphate (dibasic), calcium phosphate (tribasic), calcium sulphate, cellulose, microcrystalline cellulose, microcrystalline silicified cellulose, powdered cellulose, dextrates, dextrose, fructose, lactitol, lactose monohydrate, magnesium carbonate, maltitol, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, pregelatinized starch, sucrose, compressible sugar, sugar spheres, talc, xylitol and combinations thereof. 36 to 60 weight % of the solid dosage form of one or more binders preferably selected from the group consisting of water, acacia mucilage, alginic acid, carbomer, carboxymethylcellulose calcium, carboxymethycellulose sodium, microcrystalline cellulose, powdered cellulose, ethyl cellulose, gelatine, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, magnesium aluminum silicate, maltodextrin, methylcellulose, polydextrose, polyethylene oxide, povidone, copovidone, sodium alginate, starch paste, pregelatinized starch, Sucrose (syrup) and combinations thereof. 5 to 20 weight % of the solid dosage form of one or more disintegrants preferably selected from the group consisting of starch, microcrystalline cellulose, alginic acid, methyl cellulose, sodium starch glycolate, croscarmellose sodium, crospovidone, calcium silicate and combinations thereof; and 0.05 to 1 weight % of the solid dosage form of one or more lubricants preferably selected from the group consisting of calcium stearate, fumaric acid, glyceryl behenate, glyceryl palmitostearate, hydrogenated vegetable oil, magnesium lauryl sulphate, magnesium stearate, polyethylene glycol 4000 or 6000, sodium lauryl sulphate, sodium stearyl fumarate, starch, stearic acid, talc, zinc stearate and combinations thereof. ### Claim 8 Solid dosage form comprising: 6 to 25 weight % of the solid dosage form oleyl phosphocholine; 20 to 35 weight % of the solid dosage form lactose, preferably lactose monohydrate; 35 to 50 weight % of the solid dosage form cellulose, preferably microcrystalline cellulose; 5 to 20 weight % of the solid dosage form croscarmellose, preferably croscarmellose sodium; 1 to 10 weight % of the solid dosage form hydroxypropylmethyl cellulose; and 0.05 to 1 weight % of the solid dosage form of a lubricant, preferably magnesium stearate. ### Claim 9 (depends on 8) Solid dosage form according to claim 8, comprising: 10 to 15 weight % of the solid dosage form oleyl phosphocholine; 25 to 30 weight % of the solid dosage form lactose, preferably lactose monohydrate; 42 to 47 weight % of the solid dosage form cellulose, preferably microcrystalline cellulose; 10 to 15 weight % of the solid dosage form croscarmellose, preferably croscarmellose sodium; 1 to 5 weight % of the solid dosage form hydroxypropylmethyl cellulose; and 0.1 to 0.3 weight % of the solid dosage form of a lubricant, preferably magnesium stearate. ### Claim 10 (depends on 8) Solid dosage form according to claim 8, comprising: 12 to 14, preferably 13, weight % of the solid dosage form oleyl phosphocholine; 27 to 29, preferably 28, weight % of the solid dosage form lactose, preferably lactose monohydrate; 43 to 45, preferably 44, weight % of the solid dosage form cellulose, preferably microcrystalline cellulose; 11 to 13, preferably 12, weight % of the solid dosage form croscarmellose, preferably croscarmellose sodium; 2 to 4, preferably 3, weight % of the solid dosage form hydroxypropylmethyl cellulose; and 0.1 to 0.3, preferably 0.2, weight % of the solid dosage form of a lubricant, preferably magnesium stearate. ### Claim 11 (depends on 1) Solid dosage form according to claim 1, wherein said form is a tablet or capsule, preferably a tablet. ### Claim 12 (depends on 11) Solid dosage form of claim 11, comprising an inner core comprised of: 12 to 14, preferably 13, weight % of the solid dosage form oleyl phosphocholine; 27 to 29, preferably 28, weight % of the solid dosage form lactose, preferably lactose monohydrate; 43 to 45, preferably 44, weight % of the solid dosage form cellulose, preferably microcrystalline cellulose; 5 to 7, preferably 6, weight % of the solid dosage form croscarmellose, preferably croscarmellose sodium; 2 to 4, preferably 3, weight % of the solid dosage form hydroxypropylmethyl cellulose; and an outer layer comprised of: 5 to 7, preferably 6, weight % of the solid dosage form croscarmellose, preferably croscarmellose sodium; and 0.1 to 0.3, preferably 0.2, weight % of the solid dosage form of a lubricant, preferably magnesium stearate. ### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) Method for the preparation of a solid dosage form according to claim 1, said method comprises: a) adding to a dry mixture comprising one or more pharmaceutically acceptable diluents/fillers, disintegrants and/or binders water, water comprising 6 to 25 weight % oleyl phosphocholine; b) drying and sieving the mixture obtained in step (a); c) adding one or more disintegrants and/or lubricants as defined in any of the claims 1 to 13 to the mixture obtained in step (b); d) mixing the mixture obtained in step (c); e) preparing an oral dosage form of the mixture of step (d), preferably by compression molding. ### Claim 14 (depends on 13) Method according to claim 13, comprising: a) adding to a dry mixture comprising lactose, preferably lactose monohydrate, cellulose, preferably microcrystalline cellulose, croscarmellose, preferably croscarmellose sodium and hydroxypropylmethyl cellulose water comprising 6 to 25 weight % oleyl phosphocholine; b) drying and sieving the mixture obtained in step (a); c) adding croscarmellose, preferably croscarmellose sodium and a lubricant, preferably magnesium stearate, to the mixture obtained in step (b); d) mixing the composition obtained in step (c); and e) preparing an oral dosage form of the mixture of step (d), preferably by compression molding. ### Claim 15 (depends on 13) Method according to claim 13, wherein sieving comprises a first sieving step, preferably through a 1400 mm sieve, before drying and a second sieving step after drying, preferably through a 710 nm sieve. ### Claim 16 (depends on 13) Solid dosage form obtainable by a method according to claim 13. ### Claim 17 (canceled) ### Claim 18 (canceled) ### Claim 19 (depends on 1) A method of treating a disease in humans or animals comprising administering an oral solid dosage form according to claim 1 to a human or animal. ### Claim 20 (depends on 19) The method of claim 19, wherein the disease comprises a parasitic disease or cancer. ### Claim 21 (depends on 20) The method of claim 20, wherein the parasitic disease comprises leishmaniasis, chagas or malaria.