Patent EA-002326-B1 (EA)
Title: Process for solubilizing pharmaceutically active ingredients in watre and in agueous vehicles
Inventor: SAETTONE MARCO FABRIZIO
IPC: A61K47/48
Filed: 1998-07-22
Abstract: 1. A process for solubilizing in water and in aqueous vehicles sparingly water-soluble pharmaceutically active substances, comprising, in sequence, the following operations: 1) forming a complex of such pharmaceutically active substance with a pharmaceutically acceptable non-ionic polymer capable of forming complexes with said pharmaceutically active substance, and isolating the complex in solid form; 2) dissolving again the thus obtained complex in an aqueous medium by means of a pharmaceutically acceptable non-ionic surfactant. 2. A process according to Claim 1, wherein said operation 1) is carried out by dissolving in one or more organic solvents, separately or together, said pharmaceutically active substance and said non-ionic polymer, then pooling the two solutions together in the event that the dissolution has been carried out separately, and co-precipitating the resulting complex by evaporation of said one or more solvents. 3. A process according to Claim 2, wherein said operation 1) comprises the following steps: 1a) combining and mixing up to dissolution, separately or together, said pharmaceutically active substance and said non-ionic polymer with said one or more organic solvents, in such a way that the composition of the resulting overall solution is as follows: from 0.05% to 10% of pharmaceutically active substance; from 1% to 50% of non-ionic polymer; and from 5% to 50% of one organic solvent or of a mixture of organic solvents, all of the above percentage amounts being by weight; and 1b) evaporating said one or more solvents to give said complex in solid form. 4. A process according to Claim 2 or 3, wherein said operation 2) comprises the following step: 2a) adding water or an aqueous vehicle and from 1% to 50% of a non-ionic surfactant to said complex in solid form. 5. A process according to any preceding Claim, wherein said pharmaceutically acceptable non-ionic polymer capable of forming complexes is chosen from the group consisting of: polyvinylpyrrolidone (PVP), cyclodextrins, polyethylene glycol (PEG), polypropylene glycol (PPG), cellulose ethers and dextran. 6. A process according to Claim 5, wherein said non-ionic polymer is soluble PVP, having an average molecular weight comprised in the range from 2,000 to 1,500,000. 7. A process according to any preceding Claim, wherein said non-ionic surfactant is chosen from the group consisting of: fatty acid esters and saccharose, fatty alcohol ethers and oligoglucosides, fatty acid esters and glycerol, fatty acid esters and sorbitan, polyethoxylated fatty acid esters and sorbitan, fatty acid esters and poly(ethylene oxide), fatty alcohol ethers and poly(ethylene oxide), alkylphenol ethers and poly(ethylene oxide), polyoxyethylene-polyoxypropylene block copolymers, and ethoxylated fats and oils. 8. A process according to Claim 7, wherein said surfactant is polyethylene glycol-glyceryl triricinoleate (PEG-GTR). 9. A process according to any of Claims 2-8, wherein said one or more organic solvents are chosen from the group consisting of: monohydric alcohols with 1-4 carbon atoms, ketones, and chlorinated solvents. 10. A process according to any of preceding Claims, wherein said pharmaceuticauly active substance is chosen from the group consisting of: forskolin, dapiprazole, tolrestat, piroxicam, formocortal, rutin, rufloxacin, and amphotericin B.