Hydrogels with increased organic solvent soluble active agent loading capacity, their preparation and the use thereof

Claim 1

A process for the preparation of a controlled, sustained release composition comprising: (a) an organic-solvent soluble active agent in an amount sufficient for the total desired dosage during the release period and distributed within (b) a water-insoluble macromer expanded hydrogel comprising the crosslinked copolymerization product of (A') about 30 to about 90% by weight of said hydrogel of (a') a water-soluble monoolefinic monomer, or mixture of said monomers, of (b') a water-soluble monoolefinic monomer, or mixture of said monomers with 1 to 50% by weight of total monomers of a water-insoluble monoolefinic monomer, or mixture of said water-insoluble monomers, with (B) about 70 to about 10% by weight of said hydrogel of a terminal diolefinic hydrophobic macromer having a molecular weight from about 400 to about 8000, said macromer having the formula ##STR2## wherein R 1 is a polycondensate chain having a molecular weight from about 200 and about 8000, which is the residue of a poly (propylene oxide) or poly(tetramethylene oxide) glycol having ether linkages; R 2 is hydrogen, methyl or --CH 2 COOR 4 wherein R 4 is hydrogen or an alkyl group with up to 10 carbon atoms; R 3 is hydrogen or --COOR 4 , with the proviso that at least one of R 2 and R 3 is hydrogen; X is oxa, --COO--, or --CONR 5 --wherein R 5 is hydrogen or alkyl of up to 5 carbon atoms and Y is a direct bond or the radical --R 6 --Z 1 --CO--NH--R 7 --NH--CO--Z 2 --, wherein R 6 is linked to X and represents branched or linear alkylene of up to 7 carbon atoms; Z 1 and Z 2 are oxa or NR 5 and R 7 is the diradical of an aliphatic or aromatic diisocyanate, with the proviso that in case Xi is oxa, Y is different from a direct bond, and R 2 and R 3 are hydrogen; comprising the steps of copolymerizing said monomer (A) and said macromer (B) in the presence of a free radical initiator at the reaction temperature between about 20° to about 150° C., in the presence or absence of a substantially inert diluent, and in the presence of an effective macromer (B) expanding amount of a macromer (B) soluble compound of the formula '--R"--O--.sub.n R" (II) wherein R' is HO--, alkoxy of up to eight carbon atoms or alkanoyloxy of up to eight carbon atoms; R" is straight or branched chain alkylene of two to six carbon atoms; R"' is hydrogen, alkyl of up to eighteen carbon atoms or alkanoyl of up to eighteen carbon atoms; and n is an integer from 1 to about 100, with the proviso that if n is 1 or R" is ethylene, R"' is alkyl of two to eighteen carbon atoms or alkanoyl of three to eighteen carbon atoms, or a mixture thereof; to form said hydrogel; and loading said active agent (a) into said hydrogel.