Process for the preparations of finely divided pharmaceutical compositions

Claim 2

A process for the preparation of an activated pharmaceutical composition, which comprises the steps of providing a solid drug that is scarcely soluble in water, dispersing the drug in water in the presence of a water-soluble high-molecular substance to form a disperse system containing the drug in the form of finely divided particles substantially not greater than 10 g in diameter, and then removing the dispersion medium 60 from the disperse system.

Claim 3

A process according to claim 1, wherein the water-soluble highmolecular substance is a cellulose derivative, a-starch, hydroxypropyl starch, pullulan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone or any mixture thereof.

Claim 4

A process according to claim 1, wherein the water-soluble highmolecular substance has thermally 12 GB 2 050 828 A 12 gelling properties, and wherein the process further includes the steps of, after the formation of the disperse system, heating the disperse system to effect gelation of the water-soluble high-molecular substance and separating the resulting gel from the liquid phase.

Claim 5

A process according to claim 3, wherein the water-soluble highmolecular substance having thermally 5 gelling properties is hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose, hydroxypropyl amylose, hydroxypropyl pullulan, or any mixture thereof.

Claim 6

A process according to any of claims 1 to 4, wherein the solid drug that is scarcely soluble in water is soluble in an aqueous alkaline solution, and wherein the step of dispersing the drug in water in the presence of a water-soluble high-molecular substance is carried out by dissolving the drug in an aqueous alkaline solution containing the water-soluble high-molecular substance and then gradually adding an acid with stirring to the resulting solution.

Claim 7

A process according to claim 5, wherein the solid drug that is scarcely soluble in water and is soluble in an aqueous alkaline solution is iopanoic acid, iothalamic acid, indomethacin, nalidixic acid, trichloromethiazide, barbital, hydrochlorothiazide, phenytoin, phenylbutazone, phenobarbital, furosemide, dehyd- rocholic acid, propylthiouracil, methylthiouracil, methotrexate, folic acid, iodamide or riboflavin.

Claim 8

A process according to any of claims 1 to 4, wherein the solid drug that is scarcely soluble in water is soluble in an aqueous acid solution, and wherein the step of dispersing the drug in water in the presence of a water-soluble high-molecular substance is carried out by dissolving the drug in an aqueous acid solution containing the water-soluble highmolecular substance and then gradually adding an alkali with stirring to the resulting solution.

Claim 9

A process according to claim 7, wherein the solid drug that is scarcely soluble in water and is soluble in an aqueous acid solution is ethyl aminobenzoate, ethioamide, ajmaline, sulphamethoxazole, sulphami nomethoxin, sulphisoxazole, tetracycline, 1-tryptophan, perphenazine maleate, norepinephrine, methyidopa or levodopa.

Claim 10

A process according to any of claims 1 to 4, wherein the solid drug that is scarcely soluble in water is soluble inorganic solvents, and wherein the step of dispersing the drug in water in the presence of a water-soluble high-molecular substance is carried out by dissolving the drug in a hydrophobic organic solvent and then emulsifying the resulting solution in water in the presence of the water-soluble high-molecular substance.

Claim 11

A process according to claim 9, wherein the hydrophobic organic solvent is a low boiling organic X solvent.

Claim 12

A process according to claim 10, wherein the low boiling organic solvent is chloroform, methylene chloride, trichloroethylene, trichloroethane, carbon tetrachloride, benzine, n-hexane, benzene, toluene, xylene, ethyl ether, isopropyl ether, methyl ethyl ketone ethyl acetate or any mixture thereof.

Claim 13

A process according to claim 9, wherein the hydrophobic organic solvent is a non-volatile oily substance that can be orally administered without any harmful effect.

Claim 14

A process according to claim 12, wherein the non-volatile oily substance is a glyceride, liquid paraffin, squalane, squalene, lecithin, pristane, a low HI-B sorbitan fatty acid ester, a low-HLB sucrose fatty acid ester, a polyglycerol fatty acid ester, or any mixture thereof.

Claim 15

A process according to any of claims 9to 13, wherein the solid drug that is scarcely soluble in water 40 and is soluble in organic solvents is ajmaline, isopropylantipyrine, quinine ethyisulphate, ethenzamide, erythromycin, erythromycin fatty acid esters, kitasamycin, chlorpropamide, chformezanone, cortisone acetate, diazepam, digitoxin, cyclophosphamide, spironolactone, nalidixic acid, amobarbital, indomethacin, josamycin, nifedipine, ubidecarenone or chloramphenicol palmitate.

Claim 16

A process according to any of claims 1 to 4, wherein the step of dispersing the drug in water in the 45 presence of a water-soluble high-molecular substance is carried out by wet-grinding the drug in an aqueous solution of the water-soluble high-molecular substance.

Claim 17

A process according to any of claims 1 to 15, which further includes the step of dry-grinding the drug before the wet-grinding operation.

Claim 18

A process according to any of claims 1 to 16, wherein the step of removing the dispersion medium 50 from the disperse system is carried out by spray-drying the disperse system.

Claim 19

A process according to any of claims 1 to 16, wherein the step of removing the dispersion medium from the disperse system is carried out by spraying the disperse system onto an excipient in a fluid-bed spray granulator.

Claim 20

A process according to any of claims 1 to 18, which further includes the step of, after the removal of the water, converting the resulting activated pharmaceutical composition into subtle granules, granules, tablets, sugar-coated tablets, capsulated drugs or suppositories.

Claim 21

A process according to claim 1, substantially as hereinbefore described with reference to any of the Examples.

Claim 22

An activated pharmaceutical composition when prepared by a process according to any of claims 1 to 60 20. Printed for Her Majesty's Stationery Office, by Croydon Printing Company Limited, Croydon Surrey, 1980. Published by the Patent Office, 25 Southampton Buildings. London, WC2A l AY, from which copies may be obtained. 1 W