Dosage form, process of making and using same

• US 6,096,339 A
• Filed: 04/04/1997
• Issued: 08/01/2000
• Est. Priority Date: 04/04/1997
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Magruder, Judy A., Ayer, Atul D., Lam, Andrew, Hamel, Lawrence G., Wong, Patrick S. L.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Seidleck, Brian K.
• Application Number:
  US08/826,642
• Time in Patent Office: 1,215 Days
• Field of Search: 424/473, 424/484, 424/469, 424/468, 424/470, 604/890.1, 604/892.1, 514/964
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

The invention disclosed pertains to a dosage form comprising an agent formulation comprising drug and pharmaceutical carrier of cooperating particle size and means for dispensing the agent formulation from the dosage form.

Claims

1. A process for providing a controlled drug rate of release from a dosage form, wherein the dosage form comprises a composition, a dose of drug in the composition, and a hydrophilic polymer in the composition;

and wherein the process comprises (1) formulating the composition with a drug possessing a size less than 150 μ

m, and (2) formulating the composition with a hydrophilic polymer of less than 250 μ

m size;

whereby, through the copresence of (1) and (2) in the composition, the drug is delivered at a controlled rate of release from the dosage form.

2. The process for providing the dosage form according to claim 1, wherein the composition is enveloped by a wall comprising means for releasing the drug from the dosage form.

3. The process for providing the dosage form according to claim 1, wherein the composition is surrounded by an outer wall and an inner subcoat, with means in the dosage form for releasing the drug from the dosage form.

4. A process for providing a controlled drug rate of release from a dosage form, wherein the dosage form comprises:

a drug composition comprising a dose of drug and a hydrophilic polymer, and a dispensing, composition comprising means for dispensing the drug composition from the dosage form; and

wherein the process comprises formulating the drug composition with a drug possessing a particle size up to 150 μ

m and with a hydrophilic polymer possessing a particle size up to 250 μ

m, which, through the cooperation of the drug particles and the hydrophilic polymer particles, and the dispensing composition assisting the drug composition, the drug is delivered at a substantially controlled rate of release from the dosage form.

5. The process for providing the drug rate of release according to claim 4, wherein the hydrophilic polymer particle cooperates with the drug particle as a pharmaceutical carrier for delivering the drug from the dosage form.

6. The process for providing the drug rate of release according to claim 4, wherein the dispensing composition assists in displacing the drug composition from the dosage form.

7. The process for providing the drug rate of release according to claim 4, wherein a wall encases both the drug composition and the dispensing composition, and comprises means for releasing the drug from the dosage form.

8. The process for providing the drug rate of release according to claim 4, wherein a wall surrounds the drug composition and the dispensing composition, a subcoat is between the wall, the drug composition and the dispensing composition, and the dosage form comprises exit means for releasing the drug from the dosage form.

9. A dosage form for the delivery of a drug, wherein the dosage form comprises:

(a) a composition comprising;

(b) a dose of drug in the composition said drug comprising a size less than 150 μ

m;

(c) a hydrophilic polymer in the composition, said polymer comprising a size less than 250 μ

m;

(d) a wall comprising a composition permeable to the passage of fluid that surrounds the composition comprising the dose of drug and the hydrophilic polymer; and

(e) means in the wall for delivering the drug at a substantially controlled rate from the dosage form.

10. A dosage form for the delivery of a drug, wherein the dosage form comprises

(a) a drug composition;

(b) a dose of drug comprising a size of less than 150 μ

m in the drug composition;

(c) a hydrophilic polymer comprising a size of less than 250 μ

m in the drug composition;

(d) a coat that surrounds the drug composition comprising means for delaying release of drug from the drug composition;

(e) a wall comprising a composition that surrounds the coat; and

,

(f) means in the dosage form for delivering the drug from the dosage form.

11. The dosage form according to claim 10, wherein the drug is a member selected from the group consisting of verapamil, nifedipine, milvadipine, flunarizine, nimodipine, diltiazem, nicardipine, nitrendipine, nisoldipine, felodipine, amlodipine, isradipine, cinnarizine, fendiline, ramipril, fusinopril, altiopril, benazepril, livenzapril, alacepril, cilazapril, cilazaprilat, perindopril, zofenopril, enalapril, lisinopril, imidapril, spirapril, rentiapril, captopril, delapril, olindapril, indolapril, and quinapril.

12. A dosage form for the delivery of a drug, wherein the dosage form comprises:

(a) a drug composition comprising a drug comprising a particle of less than 150 μ

m size and a pharmaceutically acceptable hydrophilic polymer carrier comprising a particle of less than 250 μ

m size;

(b) a displacement composition in contact with the drug composition comprising means for causing fluid to enter the displacement composition, whereby the displacement composition increases in volume and displaces the drug composition from the dosage form;

(c) a wall, comprising means for permitting a fluid to enter the dosage form, that surrounds the drug composition and the displacement composition; and

(d) means in the wall for delivering the drug as a substantially constant rate over a dispensing time.

13. The dosage form for delivering the drug according to claim 12, wherein the drug is a member selected from the group consisting of a calcium channel blocker, an angiotensin enzyme inhibitor, alpha receptor blocking drugs, beta receptor blocking drugs, antianginal drugs, antiarrhythmias drugs, antiembolus drugs, antihypertensive drugs, digitalis drugs, hemorheologic drugs, inotropic drugs, myocardial infarction prophylasix drugs, cerebral vasodilators, coronary vasodilators, peripheral vasodilators and vasopresor drugs.

14. A dosage form for delivering a drug orally to a patient in need of a drug, wherein the dosage form comprises:

(a) a drug composition comprising a drug comprising a particle size up to and including 150 μ

m, and a hydrophilic polymer carrier for the drug comprising a particle size up to and including 250 μ

m;

(b) a displacement composition in contrast with the drug composition comprising a polymer that expands in the presence of fluid for displacement of the drug composition from the dosage form;

(c) a coat, free of drug, which surrounds the drug and the displacement composition for slowing the passageway of fluid into the dosage form;

(d) a wall tha surrounds the coat and is permeable to the passage of fluid; and

,

(e) means in the dosage form for delivering the drug from the dosage form at a substantially constant rate over time.

15. The dosage form for delivering the drug according to claim 14, wherein the drug composition comprises a member selected from the group consisting of an antioxidant and a surfactant.

16. The dosage form for delivering the drug according to claim 14, wherein the drug in the drug is a member selected from the group consisting of verapamil, isradipine, nifedipine, nilvadipine, flunarizine, nimodipine, diltiazem, nicardipine, nitrendipine, nisoldipine, felodipine, amlodipine, cinnarizine, fendiline, prazosin, clonidine, pinacidil, alfuzosin, quinapril, indolapril, olindapril, delapril, captopril, rentrapil, spirapril, imidapril, lisinopril, enalapril, enalaprilat, zofenopril, perindopril, cilazaprilat, alacepril, libenzapril, benazepril, altropril, fosinopril and ramipril.

17. A method for the management of blood pressure in a patient, wherein the method comprises:

(a) admitting orally into the patent a therapeutic composition comprising a dose of drug indicated for the management of blood pressure with the drug possessing a particle size of less than 150 μ

m, and a pharmaceutically acceptable hydrophilic carrier for the drug possessing a particle size of less than 250 μ

m; and

,

(b) managing the blood pressure by codelivering the drug and the accompanying polymer at a substantially constant rate of release from the composition to provide an effective dose for managing the blood pressure of the patient.

18. The method for the management of blood pressure according to claim 17, wherein a wall with means for providing a passage therethrough surrounds the therapeutic composition.

19. The method for the management of blood pressure according to claim 17, wherein a coat comprising a hydroxyalkylcellulose surrounds the therapeutic composition and a wall comprising a member selected from cellulose ester, cellulose ether and cellulose ester-ether surrounds the coat, with means in the coat and in the wall for delivering the drug and polymer from the composition.

20. The method for the management of blood pressure according to claim 17, wherein the drug is a member selected from the group consisting of alpha-receptor, beta-receptor, antihypertensive, alpha-blocker, beta-blocker, calcium channel blocker, angiotensin enzyme inhibitor, vasodilator, cerebral, coronary, peripheral, and alpha adrenergic drugs.

21. A method for the management of the systemic physiology of a patient, wherein the method comprises:

(a) admitting orally into the patient a therapeutic composition comprising a dose of drug indicated for the management of a systemic physiology with the drug possessing an average particle size of less than 150 μ

m, and a therapeutically acceptable hydrophilic polymer possessing an average particle size of less than 250 μ

m for delivering the drug from the therapeutic composition; and

a delivery composition in contact with the therapeutic composition comprising a therapeutically acceptable hydrophilic polymer possessing a greater number-average molecular weight than the hydrophilic polymer present in the therapeutic composition for aiding in delivering the drug from the therapeutic composition; and

,

(b) managing the systemic physiology of the patient by the codelivery of the drug and the polymer at a substantially constant rate of release from the therapeutic composition aided by the delivery composition to provide an effective dose for the management of the systemic physiology of the patient.

22. The method for the management of the systemic physiology of a patient according to claim 21, wherein a wall with means for providing a passage therethrough surrounds the therapeutic composition and the delivery composition.

23. The method for the management of the systematic phisiology of a patient according to claim 21, wherein an inner coat surrounds both the therapeutic composition and the delivery composition, and an outer wall surrounds the inner coat, with means in the coat and wall for delivery of the drug from the therapeutic composition.

24. The method for the management of the systemic physiology of the patient according to claim 21, wherein the management of the systemic physiology comprises administering a drug comprising vasodilating, hypotensive, and antianginal therapy.

25. The method for the management of the systemic physiology of the patient according to claim 21, wherein the management of the systemic physiology comprises administering a drug for alleviating angiotensin related hypertension in the patient.

26. A method of timetherapy for delivering a drug to a patient at a selected time, wherein the method comprises administering orally to the patient a therapeutic composition comprising a dose of drug possessing an average particle size up to 150 μ

m and a pharmaceutically acceptable polymer possessing an average particle size up to 250 μ

m, and means for governing the release of drug from the therapeutic composition, whereby the drug is released by the means in a substantially constant rate of release at the selected time for timetherapy.

27. A method for timetherapy for delivering a drug to a patient over a selected time for the management of hypertension, wherein the method comprises orally administering to the patient a therapeutic composition comprising a calcium channel blocker drug and an angiotensin converting enzyme inhibitor drug possessing an average particle size up to 150 μ

m and a pharmaceutically acceptable polymer possessing an average particle size up to 250 μ

m, and means for governing the release of the drugs from the therapeutic composition, whereby the drugs are timed-release in a substantially constant dose over the selected time for the timetherapy management of hypertension.

28. The method of timetherapy for delivering a drug to a patient according to claim 27, wherein the calcium channel blocker is a member selected from the group consisting of nifedipine, isradipine, nilvadipine, verapril, flunarizine, nimodipine, diltiazem, nicardipine, norverapamil, nitrendipine, nisoldipine, felodipine, amlodipine, cinnarizine, fendiline, ramipril, fosinopril, altiopril, benazepril, libenzapril, alacepril, cilazapril, cilazaprilat, perindopril, zofenopril, enalapril, lisinopril, imidapril, spirapril, rentiapril, captopril, delapril, alindapril, indolapril, and quinapril.

29. The method of timetherapy for the delivery of a drug to a patient according to claim 27, wherein the method comprises administering a drug pair to the patient in a hypertension pressure lowering effective dose, and wherein the drug pair comprises diltiazem and captopril.

30. The method of timetherapy for the delivery of a drug to a patient according to claim 27, wherein the therapeutic composition comprises a member selected from the group consisting of an antioxidant, and a surfactant.

31. The method of timetherapy for the delivery of a drug to a patient according to claim 27, wherein the timetherapy delays the delivery of drug for 2 to 6 hours and then delivers the drug for up to 15 hours.