Process for the preparation of swellable microspheres and deformable

摘要

A method of making a microsphere preparation, comprising: a) forming a first solution having a pH of at least 3 comprising: (i) water; (Ii) at least one mon 5 miscible omero water selected from the group consisting of acrylic acid, ácidometacrílico, salts of acrylic acid and methacrylic acid, acrylamide, methacrylamide, N-substituted acrylamides, methacrylamides, N-substituted acrylate, 2-hydroxyethyl and 2-hydroxyethyl methacrylate; provided that: The first solution does not contain a monomer selected from the group consisting of 2-acryloylethanesulfonic acid, 2-metacriloiletanosulfónico, salts of 2-acryloyl and 2-metacriloiletanosulfónico acid, styrene sulfonic acid and salts styrene sulfonic acid; (Iii) a crosslinking agent which is miscible in the first solution in less than or equal to 5 mol%, relative to the total moles of monomer and crosslinking agent, said agent selected from theGroup crosslinked consisting of N, N ' -methylene-bis-acrylamide, N, N'-methylene bis-methacrylamide, N-methylolacrylamide, N-methylolmethacrylamide, glycidyl acrylate, glycidyl methacrylate, polyethylene glycol diacrylate, dimethacrylate depolietilenglicol, polyvalent metal salts of acrylic acid and methacrylic acid, fosfoacrilatos divinylbenzene, divinylbenzene, divinylphenylphosphine, divinyl sulfone, 1,3-divinyltetramethyldisiloxane, 3,9-divinyl-2,4,8,10-tetraoxaspiro [5,5] undecane, fosfometacrilatos, ethylene glycol diglycidyl ether, glycerol triglycidyl ether, glicerin- diglycidyl ypolietilenglicol diglycidyl ether; (Iv) a water-soluble protective colloid; (V) an emulsifier; and (vi) an aqueous soluble azoinitiator low temperature: b) forming a second solution comprising a mixture of methylene chloride and chloroform or decloruro mixture of methylene chloride and a solvent or solvent mixture having a sum of differences in parameters desolubilidad Hansen regard to Hansen solubility parameters of less than 0.21 chloroform, and organic soluble protective uncoloide; c) forming a first stirring suspension comprising the first and second solution at a temperaturapor below the initiation temperature azoinitiator of (a); d) raising the temperature of the first suspension under stirring at a temperature that is activated elazoiniciador aqueous soluble at low temperature; e) stirring the first slurry to form a second suspension which comprising a gelatinososuspendido precipitate in an organic liquid phase, wherein the microspheres are formed; f) cooling to allow the second suspension to a temperature which is at or below 30 ° C while stirring suspension lasegunda; g) washing the second suspension at least once with a dehydrating solvent in which the water is removed delas microspheres prepared by forming a microsphere; h) recovering the microspheres prepared.