Rapid releasing triamterene containing gelatin capsule dosage forms for once daily antihypertensive use

• US 4,681,765 A
• Filed: 09/13/1984
• Issued: 07/21/1987
• Est. Priority Date: 09/13/1984
• Status: Expired due to Term

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Guley, Paul C.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US06/650,035
• Time in Patent Office: 1,041 Days
• Field of Search: 514/869, 514/960, 514/962, 514/778, 514/781, 424/37, 424/156, 424/21
• US Class Current: 424/456
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 9/4841 Filling excipients; Inactive ingredients
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077

Abstract

A gelatin capsule dosage form containing triamterene, 2,4,7-triamino-6-phenylpteridine, which results in rapid dissolution of the active ingredient. The dosage form comprises the pharmaceutical binder methylcellulose in combination with low doses of a surfactant or a carbonate salt as disintegrants.

Claims

1. Method of producing triamterene and hydrochlorothiazide capsules by mixed granulation comprising the steps:

(1) blending triamterene, methylcellulose, lactose, sodium starch glycolate, microcrystalline cellulose, and talc

(2) adding water to the blend of step 1 and mixing till granulated

(3) milling and drying the wet granulation of step 2

(4) blending the dried granulation of step 3 with hydrochlorothiazide, calcium carbonate, sodium croscarmellose and magnesium stearate and

(5) milling, and blending the blend of step 4 and encapsulating.

2. Method of treating hypertension by the administration of a gelatin capsule dosage unit comprising triamterene, propranolol long acting spheres, hydrochlorothiazide, and

(a) a rapid dispersing amount of a calcium, magnesium, ammonium, aminoacid, or alkali metal nontoxic carbonate or bicarbonate salt in the presence of adjunctive disintegrant aids selected from the group consisting of sodium starch glycolate, sodium croscarmellose and methylcellulose in the absence of a surfactant.

3. An improved rapid dispersing gelatin capsule dosage unit comprising triamterene in the presence of adjunctive disintegrant aids selected from the group consisting of sodium starch glycolate, sodium croscarmellose, and methylcellulose, wherein the improvement comprises the addition of a rapid dispersing amount of a calcium, magnesium, ammonium, aminoacid, or alkali metal nontoxic carbonate or bicarbonate salt in the absence of a surfactant.

4. The gelatin capsule of claim 3 in which the carbonate salt is calcium carbonate.

5. The gelatin capsule of claim 4 in which the triamterene is present in an amount of from 5 mg. to 100 mg., the carbonate salt is present in an amount of from about 4% to about 40% and the adjunctive disintegrant aids are present in an amount of from about 2% to about 15% by weight of the ingredients in the formula.

6. An improved rapid dispersing gelatin capsule dosage unit comprising triamterene and hydrochlorothiazide in the presence of adjunctive disintegrant aids selected from the group consisting of sodium starch glycolate, sodium croscarmellose, and methylcellulose, wherein the improvement comprises the addition of a rapid dispersing amount of a calcium, magnesium, ammonium, aminoacid, or alkali metal nontoxic carbonate or bicarbonate salt in the absence of a surfactant.

7. The gelatin capsule of claim 6 in which the carbonate salt is calcium carbonate.

8. The gelatin capsule of claim 6 in which the triamterene is present in an amount of from 5 mg. to 100 mg. and the hydrochlorothiazide is present in an amount of from 2 mg. to 250 mg., the carbonate salt is present in an amount of from about 4% to about 40% and the adjunctive ingredient aids are present in an amount of from about 2% to about 15% by weight of the ingredients in the formula.

9. An improved rapid dispersing gelatin capsule dosage unit comprising triamterene, hydrochlorothiazide and propranolol hydrochloride in the presence of adjunctive disintegrant aids selected from the group consisting of sodium starch glycolate, sodium croscarmellose, and methylcellulose, wherein the improvement comprises the addition of a rapid dispersing amount of a calcium, magnesium, ammonium, aminoacid, or alkali metal nontoxic carbonate or bicarbonate salt in the absence of a surfactant.

10. The gelatin capsule of claim 9 in which the carbonate salt is calcium carbonate.

11. The gelatin capsule of claim 9 in which the triamterene is present in an amount of from about 5 mg. to about 100 mg. and the hydrochlorothiazide is present in an amount of from about 2 mg. to about 250 mg., and the propranolol long acting spheroids are present in an amount from 60 mg. to 320 mg., the carbonate salt is present in an amount of from about 4% to about 40% and the adjunctive disintegrant aids are present in an amount of from about 2% to about 15% by weight of the ingredients in the formula.