Dipyridamole-containing pharmaceutical form

• US 4,427,648 A
• Filed: 06/17/1982
• Issued: 01/24/1984
• Est. Priority Date: 06/19/1981
• Status: Expired due to Term

• Current Assignee: Dr KARL Thomae GmbH D-7950 Biberach An Der RISS West Germany
• Original Assignee: Dr. Karl Thomae GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Gruber, Peter, Schepky, Gottfried, Brickl, Rolf, Bozler, Gerhard
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/389,282
• Time in Patent Office: 586 Days
• Field of Search: 424/19-22, 424/32, 424/35, 424/37, 424/38, 424/251, 424/267
• US Class Current: 424/459
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

This invention relates to vehicles for the administration of dipyridamole. More specifically, this invention relates to a method of treating cardiovascular disorders in a host in need of such treatment which comprises administering to said host a cardiovascularly effective amount of a composition comprised of (i) dipyridamole or an acid addition salt thereof and (ii) at least one pharmacologically acceptable acid or acid substance, the total amount of acid from acid addition salt present and acid or acid substance being in a ratio of at least about 5 acid equivalents to 1 mol of dipyridamole, preferably in the form of particles having particle sizes of from about 0.1 to 2.0 mm.

Claims

1. A method of treating cardiovascular disorders in a host in need of such treatment which comprises administering to said host a cardiovascularly effective amount of an uncoated composition consisting essentially of (i) dipyridamole or an acid addition salt thereof and (ii) at least one pharmacologically acceptable acid or acid substance, the total amount of acid from acid addition salt present and acid or acid substance being in a ratio of at least about 5 acid equivalents to 1 mol of dipyridamole.

2. The method of claim 1, wherein the total amount of acid from acid addition salt present and acid or acid substance is in a ratio of from about 10 to 30 acid equivalents to 1 mol of dipyridamole.

3. The method of claim 1, wherein the pharmacologically acceptable acid or acid substance is selected from the group consisting of tartaric acid, citric acid, fumaric acid, succinic acid, malic acid, ascorbic acid, adipic acid, sodium or potassium salts of said acids, sodium or potassium hydrogen sulfate, betaine hydrochloride, anhydrides of succinic or glutaric acid which hydrolyse in water to form acids, D-glucuronic acid-γ

-lactone, and mixtures thereof.

4. The method of claim 1 or 2, wherein the pharmacologically acceptable acid or acid substance is fumaric acid.

5. The method of claim 1, wherein the composition is in the form of granules.

6. The method of claim 5, wherein the granules have particle sizes of from about 0.1 to 2.0 mm.

7. The method of claim 6, wherein the granules have particle sizes of from about 0.25 to 1.25 mm.

8. The method of claim 5, wherein the granules are contained in hard gelatin capsules.

9. The method of claim 1, wherein the composition is in the form of pellets.

10. The method of claim 9, wherein the pellets have diameters of from about 0.1 to 2.0 mm.

11. The method of claim 10, wherein the pellets have diameters of from about 0.5 to 1.5 mm.

12. The method of claim 9, wherein the pellets are contained in hard gelatin capsules.

13. The method of claim 1, wherein the composition is in the form of tablets or tablet cores.

14. The method of claim 1, wherein the composition also comprises conventional pharmacological additives.

15. The method of claim 14, wherein the additives are selected from the group consisting of water-soluble binders, mucilaginous excipients, water-repellent excipients, and mixtures thereof.

16. The method of claim 15, wherein the additives are selected from the group consisting of methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, polyacrylic acids, fats, and mixtures thereof.

17. The method of claim 1, wherein the composition is in the form of particles having a coating comprised of a lacquer which permits the release of at least 90% of the dipyridamole in the gastrointestinal tract over a period of two hours.

18. The method of claim 1, wherein the composition comprises tablet cores prepared by compressing granules consisting of dipyridamole or an acid addition salt thereof, acid or acid substance, lubricant, and other conventional additives to form uncoated tablet cores and then coating said uncoated tablet cores with a flavor-masking coating or a lacquer coating which permits the release of at least 90% of the dipyridamole in the gastrointestinal tract over a period of two hours.

19. The method of claim 1, wherein the composition comprises cores prepared by (a) moist or dry granulation of (i) dipyridamole or an acid addition salt thereof and (ii) acid or acid substance to form a granulate;

(b) addition of further, conventional excipients to said granulate;

(c) compression of said granulate to form uncoated cores; and

(d) coating of said uncoated cores with a flavor-masking coating or a lacquer coating which permits the release of at least 90% of the dipyridamole in the gastrointestinal tract over a period of two hours.

20. The method of claim 1, wherein the composition comprises cores prepared by (a) moist or dry granulation of (i) dipyridamole or an acid addition salt thereof and (ii) conventional excipients to form a granulate;

(b) addition of one or more acids or acid substances and lubricant to said granulate;

(c) compression of said granulate to form uncoated cores; and

(d) coating of said uncoated cores with a flavor-masking coating or a lacquer coating which permits the release of at least 90% of the dipyridamole in the gastrointestinal tract over a period of two hours.

21. The method of claim 18, 19, or 20, wherein the coating is a flavor-masking coating.

22. The method of claim 18, 19, or 20, wherein the coating is a lacquer coating which permits the release of the dipyridamole in the gastrointestinal tract over a period of two hours.