Drug delivery system

• US 4,973,469 A
• Filed: 08/17/1989
• Issued: 11/27/1990
• Est. Priority Date: 02/03/1986
• Status: Expired due to Term

• Current Assignee: Elan Pharma International Limited (Perrigo Company PLC)
• Original Assignee: Elan Corporation PLC (Perrigo Company PLC)
• Inventors: Mulligan, Seamus, Sparks, Randall T.
• Primary Examiner(s): Griffin, Ronald W.
• Application Number:
  US07/395,184
• Time in Patent Office: 467 Days
• Field of Search: 514/356, 514/964, 514/965, 424/461, 424/462, 424/469, 424/486, 424/488
• US Class Current: 424/461
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Abstract

A controlled release formulation comprising an adsorbate of a mixture of a pharmaceutically useful active ingredient and an inactive substance adsorbed on a cross-linked polymer. The inactive substance is selected to modify the dissolution of the active ingredient from the cross-linked polymer in vivo.

Claims

1. A controlled release formulation comprising an adsorbate of a mixture of 1 part by weight of a pharmaceutically useful active ingredient in substantially amorphous form and from 0.1 to 10 parts by weight of an inactive substance adsorbed on a cross-linked polymer in a ratio of 1 part by weight of said mixture to 0.5-20 parts by weight of cross-linked polymer, said inactive substance being selected to modify the dissolution of the active drug from the cross-linked polymer in vivo, wherein the inactive substance is a substance whose solubility in aqueous media is inversely proportional to that of the active ingredient, with the proviso that the active ingredient is not a dihydropyridine when the inactive substance is polyvinylpyrrolidone with an average molecular weight in the range 15,000 to 50,000 and the cross-linked polymer is cross-linked polyvinylpyrrolidone.

2. A controlled release formulation according to claim 1, wherein the inactive substances is present in an amount of 0.5-3 parts by weight relative to 1 part by weight of the active ingredient.

3. A controlled release formulation according to claim 1, which contains 1 part by weight of said mixture relative to 1-10 parts by weight of cross-linked polymer.

4. A controlled release formulation according to claim 1, wherein the cross-linked polymer is a cross-linked polyvinylpyrrolidone, carboxymethylcellulose or methylcellulose.

5. A controlled release formulation according to claim 1, wherein the inactive substance is a natural or synthetic, inert, pharmaceutically acceptable polymer.

6. A controlled release formulation according to claim 5, wherein the inactive substance polymer is selected from the group consisting of substituted or unsubstituted alkylcelluloses, copolymers of acrylic and methacrylic acid esters, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, galactomannone, carboxypolymethylene and shellac or mixtures thereof.

7. A controlled release formulation according to claim 6, wherein the inactive substance polymer is selected from the group consisting of methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose or sodium carboxymethylcellulose.

8. A controlled release formulation according to claim 1, wherein the inactive substance is an organic acid selected from the group consisting of adipic acid, ascorbic acid, citric acid, fumaric acid, maleic acid, succinic acid or tartaric acid.

9. A controlled release formulation according to claim 1, wherein the inactive substance is a sugar.

10. A controlled release formulation according to claim 1, wherein the active ingredient is selected from the group consisting of chlorpheniramine, diclofenac, theophylline, felodipine, nifedipine, nicardipine, nitrendipine, 4-(2,1,3-benzoxadiazol-4-yl)-2, 6-dimethyl-1,4-dihydro-3-isopropyloxycarbonyl-pyridine-5-carboxylic acid methyl ester, co-dergocrine mesylate, oxendolone, azidothymidine and spironolactone.

11. A controlled release drug delivery system which comprises an adsorbate as defined in claim 1.

12. A controlled release drug delivery system according to claim 11, which is in the form of capsules or tablets.