초록 ▼

Nanometer particles of poorly water-soluble or substantially water-insoluble compound are produced by finely-spraying a non-aqueous solution of said compound into a heated and fluidized bed of carrier excipient. The resulting product consists of a free flowing mixture of relatively large particles o

Nanometer particles of poorly water-soluble or substantially water-insoluble compound are produced by finely-spraying a non-aqueous solution of said compound into a heated and fluidized bed of carrier excipient. The resulting product consists of a free flowing mixture of relatively large particles of carrier excipient and nanometer sized particles (less than 3 μm)) of compound.

대표청구항 ▼

What is claimed is: 1. A process for producing a mixture of nanometer particles of a poorly water soluble or substantially water-insoluble pharmaceutical compound and a carrier excipient, said process comprising, spraying a solution of a water-insoluble or poorly water soluble pharmaceutical compou

What is claimed is: 1. A process for producing a mixture of nanometer particles of a poorly water soluble or substantially water-insoluble pharmaceutical compound and a carrier excipient, said process comprising, spraying a solution of a water-insoluble or poorly water soluble pharmaceutical compound in at least one organic solvent into a fluidized bed of carrier excipient particles, under conditions that allow for a substantial amount of organic solvent to be removed from said solution, such that a mixture of particles of said pharmaceutical compound having a volume-weighted mean diameter of less than or equal to 3000 nm and of carrier excipient is formed. 2. The process of claim 1, wherein said particles of said pharmaceutical compound have a volume-weighted mean diameter from about 1000 nm to about 2000 nm. 3. The process of claim 1, wherein said particles of said pharmaceutical compound have a volume-weighted mean diameter of less than 1000 nm. 4. The process of claim 1, wherein the resulting particles of pharmaceutical compound have a volume-weighted mean diameter of about 50 nm to about 1000 nm. 5. The process of claim 1, wherein the resulting particles of pharmaceutical compound have a volume-weighted mean diameter of about 300 to about 800 nm. 6. The process of claim 1, wherein the pharmaceutical compound is dissolved in a liquid medium comprising at least one non-aqueous solvent prior to spraying. 7. The process of claim 6, wherein said solution further comprises an aqueous solvent. 8. The process of claim 1, wherein said pharmaceutical compound is selected from analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antiepileptics, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives, astringents, beta-adrenoceptor blocking agents, contrast media, corticosteroids, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin, prostaglandins, radio-pharmaceuticals, sex hormones, anti-allergic agents, stimulants, sympathomimetics, thyroid agents, vasodilators and xanthines. 9. The process of claim 1, wherein said pharmaceutical compound is a steroid. 10. The process of claim 9, wherein said pharmaceutical compound is a neuroactive steroid. 11. The process of claim 10, wherein said neuroactive steroid is selected from the group consisting of 3α-hydroxy-3β-methyl-5α-pregnan-20-one (ganaxolone), 3α-hydroxy-3β-trifluoromethyl-19-nor-5β-pregnan-20-one, 2β-ethynyl-3α-hydroxy-5α-pregnan-20-one, and 3α,21-dihydroxy-3α-trifluoromethyl-19-nor-5β-pregnan-20-one. 12. The process of claim 1, wherein said pharmaceutical compound is a semicarbazone or thiosemicarbazone. 13. The process of claim 12, wherein said semicarbazone is selected from the group consisting of 4-(4-fluorophenoxy) benzaldehyde semicarbazone and 4(3,4-methylenedioxyphenoxy) benzaldehyde semicarbazone. 14. The process of claim 1, wherein the weight ratio of said excipient is one to 50 parts by weight to one part by weight of the pharmaceutical compound. 15. The process of claim 1, wherein said excipient is a sugar or sugar alcohol having a molecular weight of less than 500. 16. The process of claim 15, wherein said sugar or sugar alcohol is selected from the group consisting of xylitol, mannitol, sorbitol, arabinose, ribose, xylose, glucose, mannose, galactose, sucrose and lactose. 17. The process of claim 16, wherein said excipient is lactose. 18. The process of claim 1, wherein said spraying occurs from one or more spraying nozzles in a fluid-bed apparatus equipped with an insert for (a) top spray using a Wurster-type column, (b) bottom spray using a Wurster-type column, or (c) tangential spray using a rotor disk. 19. The process of claim 1, wherein said solution of the pharmaceutical compound further comprises one or more other substances that alter the release profile of the compound from the resulting particles. 20. The process of claim 19, wherein said one or more other substances are selected from the group consisting of gelatin, casein, lecithin, gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glyceryl monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene caster oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycols, polyoxyethylene stearates, colloidol silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethycellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, and polyvinylpyrrolidone. 21. The process of claim 1, wherein said at least one organic solvent is a mixture of non-aqueous solvents that is used to increase the solubility of the pharmaceutical compound or to decrease the volatility of one of said mixture of solvents having a low boiling point.