TRI-MOLECULAR COMPLEXES AND THEIR USE IN DRUG DELIVERY SYSTEMS
This invention relates to macromolecular complexes useful in drug delivery systems, specifically tri-molecular complexes made between a water-soluble polymer and an acid-insoluble polymer in presence of a bridging molecule. In one aspect, the invention relates to a tri-molecular complex comprising gelatin, acrylic acid/methacrylic acid copolymers, and arginine for use in a soft capsule dosage form. In another aspect, the invention is directed to a tri-molecular complex a hydrophilic, film-forming, water-soluble polymer, a second water-soluble polymer, and a bridging molecule, wherein the second water-soluble polymer is less water-soluble than the hydrophilic, film-forming, water-soluble polymer.
1 . A tri-molecular complex for use in enteric drug delivery systems comprising:
(a) a hydrophilic, film-forming, water-soluble polymer;
(b) an acid-insoluble polymer; and
(c) an amino acid.
2 . The tri-molecular complex according to claim 1 , further comprising an aqueous solvent.
3 . The tri-molecular complex according to claim 1 , further comprising a plasticizer.
4 . The tri-molecular complex according to claim 1 , wherein the amino acid is arginine.
5 . The tri-molecular complex according to claim 1 , wherein the water-soluble polymer is gelatin, the acid-insoluble polymer is acrylic acid-methacrylic acid copolymers, and the amino acid is arginine.
6 . The tri-molecular complex according to claim 3 , wherein the plasticizer is selected from the group consisting of glycerin, triethylcitrate, and mixtures thereof.
7 . The tri-molecular complex according to claim 5 , wherein the amount of acrylate-methacrylate copolymers is at least about 25% by weight of the total amount of acrylate-methacrylate copolymers and gelatin.
8 . The tri-molecular complex according to claim 6 , wherein the plasticizer is a mixture of glycerin and triethylcitrate.
9 . The tri-molecular complex according to claim 5 , further comprising glycerin.
10 . A tri-molecular complex for use in controlling the release of a therapeutic or diagnostic agent comprising:
(a) a hydrophilic, film-forming, water-soluble polymer;
(b) a second water-soluble polymer; and
(c) a bridging molecule,
wherein the second water-soluble polymer is less water-soluble than the hydrophilic, film-forming, water-soluble polymer.
11 . The tri-molecular complex according to claim 10 , wherein the second water-soluble polymer is a cellulosic polymer selected from the group consisting of a ethyl cellulose, cellulose, carboxymethyl cellulose, and mixtures thereof.
12 . The tri-molecular complex according to claim 10 , wherein the second water-soluble polymer is an acrylate-methacrylate polymer.
13 . A method of preparing a tri-molecular complex comprising the following steps: (1) suspending the acid-insoluble polymer in an acidic aqueous system with low buffer capacity; (2) mixing the water-soluble polymer with an amino acid; and (3) mixing the product of steps (1) and (2) to yield the tri-molecular complex.