# US 8,771,739 B2 · Pharmaceutical compositions 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 8,771,739 B2 - Document ID: US8771739B2 - Status: Granted - Kind: B2 - Application number: 11/763,578 - Filed: 2007-06-15 - Published: 2008-10-23 - Granted: 2014-07-08 - Earliest claimed: 1999-12-23 - Assignees: Mayne Pharma International Pty Ltd. - Applicants: David Hayes; Angelo M. Morella - Inventors: David Hayes; Angelo M. Morella - Web page: https://patentgrep.com/patent/US8771739B2 ## CPC - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 9/146: {with organic macromolecular compounds} - A61P 31/10: Antimycotics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/4866: {Organic macromolecular compounds} - 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 The present invention provides a pharmaceutical composition of a practically insoluble drug, wherein the composition may be administered with food or without food. The composition may be in the form of a solid dispersion of the practically insoluble drug and a polymer having acidic functional groups, and the composition may in vitro form a suspension. ## Claims ### Claim 1 A pharmaceutical composition comprising a solid dispersion of itraconazole and a polymer having acidic functional groups, wherein during in vitro dissolution testing the composition forms a suspension of a homogeneous dispersion of particles, and wherein the polymer comprises hydroxypropyl methylcellulose phthalate; wherein the ratio of itraconazole to polymer is in the range of from 1:1 to 1:3, and the composition provides a mean AUC of at least 800 ng·h/ml after administration in the fasted state. ### Claim 2 (depends on 1) The pharmaceutical composition according to claim 1, wherein the particles of the suspension diffract light such that the suspension presents as a cloudy suspension, and wherein the particles of the suspension are of a size less than 10 micrometer but greater than 1 nm. ### Claim 3 (depends on 1) The pharmaceutical composition according to claim 1, wherein a portion of the particles is in microparticulate form and a portion of the particles is in nanoparticulate form. ### Claim 4 (depends on 1) The pharmaceutical composition according to claim 1, wherein at least a portion of the particles of the suspension are of a size less than 450 nm but greater than 1 nm, such that after passing the suspension through a 450 nm filter, the suspension remains cloudy. ### Claim 5 (depends on 1) The pharmaceutical composition according to claim 1, wherein the suspension is present during in vitro dissolution testing at a pH in the range of from pH 4.0 to pH 8.0. ### Claim 6 (depends on 1) The pharmaceutical composition according to claim 1, wherein the suspension is present during in vitro dissolution testing at a pH in the range of from pH 5.5 to pH 7.5. ### Claim 7 (depends on 5) The pharmaceutical composition according to claim 5, wherein the in vitro dissolution testing includes an acidic pre-treatment step. ### Claim 8 (depends on 6) The pharmaceutical composition according to claim 6, wherein the in vitro dissolution testing includes an acidic pre-treatment step. ### Claim 9 (depends on 7) The pharmaceutical composition according to claim 7, wherein the acidic pre-treatment step is suspension in a dissolution medium at a pH of about 1.2 for a period of about 20 minutes. ### Claim 10 (depends on 8) The pharmaceutical composition according to claim 8, wherein the acidic pre-treatment step is suspension in a dissolution medium at a pH of about 1.2 for a period of about 20 minutes. ### Claim 11 (depends on 1) The pharmaceutical composition according to claim 1, wherein the solid dispersion is formed by spray drying techniques. ### Claim 12 (depends on 11) The pharmaceutical composition according to claim 11, wherein the polymer is dispersed within a solvent prior to dispersion of itraconazole, wherein the solvent is one or more of the group comprising methylene chloride, chloroform, ethanol, methanol, propan-2-ol, ethyl acetate, acetone and water. ### Claim 13 (depends on 1) The pharmaceutical composition according to claim 1, wherein the bioavailability of itraconazole in the pharmaceutical composition is at least twice the bioavailability of itraconazole per se. ### Claim 14 (depends on 1) The pharmaceutical composition according to claim 1, wherein the composition has a reduced food effect compared to itraconazole per se. ### Claim 15 (depends on 1) A pharmaceutical dosage form containing a therapeutically effective amount of the pharmaceutical composition of claim 1. ### Claim 16 (depends on 15) The pharmaceutical dosage form according to claim 15 including one or more excipients selected from the group consisting of disintegrants, diluents, fillers, lubricants, glidants, colorants and flavors. ### Claim 17 (depends on 15) The pharmaceutical dosage form according to claim 15, wherein the dosage form is a capsule or a tablet. ### Claim 18 (depends on 16) The pharmaceutical dosage form according to claim 16, wherein the dosage form is a capsule or a tablet. ### Claim 19 (depends on 1) A process for preparing a pharmaceutical composition according to claim 1, the process including the steps of: (a) adding hydroxypropyl methylcellulose phthalate to a solvent to form a dispersion; (b) adding itraconazole to the dispersion to form a solution; and (c) spray drying the solution to form the pharmaceutical composition in the form of a solid dispersion. ### Claim 20 (depends on 19) The process according to claim 19, wherein the solvent is methylene chloride. ### Claim 21 (depends on 19) The process according to claim 19, wherein the solid dispersion is subsequently blended with one or more excipients to produce a powder for use in a pharmaceutical dosage form. ### Claim 22 (depends on 20) The process according to claim 20, wherein the solid dispersion is subsequently blended with one or more excipients to produce a powder for use in a pharmaceutical dosage form. ### Claim 23 (depends on 21) The process according to claim 21, wherein the blending occurs with grinding. ### Claim 24 (depends on 22) The process according to claim 22, wherein the blending occurs with grinding. ### Claim 25 (depends on 1) The pharmaceutical composition according to claim 1, wherein the composition provides a mean AUC of at least 800 ng·h/ml after administration of 100 mg itraconazole in the fasted state.