Colonic-targeted oral drug-dosage forms based on crosslinked hydrogels containing azobonds and exhibiting PH-dependent swelling
First Claim
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1. A crosslinked hydrogel comprised of:
- (a) at least one ethylenically unsaturated comonomer containing no ionizable group;
(b) at least one ethylenically unsaturated comonomer containing an ionizable group; and
(c) a crosslinking agent containing an aromatic azobond,said copolymer being crosslinked beyond the gel point and containing an amount of (b) such that the hydrogel exhibits pH-dependent swelling wherein the hydrogen imbibes at least about 10% more water at the pH found in the human colon than at the pH found in the human stomach.
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Abstract
Colonic-targeted oral drug dosage forms composed of a drug confined within a crosslinked hydrogel that exhibits pH-dependent swelling and is composed of an ionizable comonomer such as acrylic acid, a nonionizable comonomer such as an acrylamide, and a crosslinking agent that contains an aromatic azobond. Selective drug release in the colon occurs by a combination of pH-dependent swelling of the hydrogel and degradation of the hydrogel by enzymatic cleavage of the azobonds by azoreductases.
63 Citations
38 Claims
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1. A crosslinked hydrogel comprised of:
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(a) at least one ethylenically unsaturated comonomer containing no ionizable group; (b) at least one ethylenically unsaturated comonomer containing an ionizable group; and (c) a crosslinking agent containing an aromatic azobond, said copolymer being crosslinked beyond the gel point and containing an amount of (b) such that the hydrogel exhibits pH-dependent swelling wherein the hydrogen imbibes at least about 10% more water at the pH found in the human colon than at the pH found in the human stomach. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 22, 23, 24, 25, 26, 27, 33, 34, 36, 37, 38)
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18. A process for making the hydrogel of claim comprising the steps of:
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forming a solution of (a), (b), and (c) wherein (c) contains at least two ethylenically unsaturated bonds in addition to said aromatic azobond; and subjecting the solution to crosslinking copolymerization conditions wherein the crosslinking copolymerization is carried out beyond the gel point. - View Dependent Claims (19, 20, 21, 35)
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28. A crosslinked hydrogel copolymer-drug conjugate useful for delivering the drug selectively to the colon comprised of:
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(a) at least one ethylenically unsaturated comonomer unit containing no ionizable group; (b) at least one ethylenically unsaturated comonomer unit containing an ionizable group; (c) at least one ethylenically unsaturated comonomer unit having a drug covalently bound thereto in an aromatic azobond; and (d) a bifunctional crosslinking agent, said copolymer being crosslinked at the gel point and containing an amount of (a) such that the copolymer exhibits pH-dependent swelling wherein the hydrogel imbibes at least about 10% more water at the pH found in the human colon than at the pH found in the human stomach. - View Dependent Claims (29, 30, 31, 32)
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Specification