Claims for Patent: 5,785,994

Summary for Patent: 5,785,994

Title:	Method for administering drug to gastrointestinal tract
Abstract:	A dosage form is disclosed that comprises means inside the dosage form for providing a substantially drug-free interval before the dosage form delivers a drug from inside the dosage form. The dosage form in an embodiment comprises a drug on the exterior of the dosage form, which drug is available for immediate delivery.
Inventor(s):	Wong; Patrick S.-L. (Palo Alto, CA), Theeuwes; Felix (Los Altos, CA), Ayer; Atul Devdatt (Palo Alto, CA), Kuczynski; Anthony L. (Palo Alto, CA)
Assignee:	ALZA Corporation (Palo Alto, CA)
Application Number:	07/862,665
Patent Claims:	1. A method for administering a drug to the gastrointestinal tract of a warm-blooded animal, which method comprises: (a) admitting an osmotic device into the gastrointestinal tract of the warm-blooded animal, said device comprising: (1) a compartment; (2) a wall that surrounds and forms the compartment, said wall comprising a composition that is permeable to the passage of fluid; (3) a first composition in the compartment comprising a viscosity of 100 centipoises to 10,000,000, said first composition drug-free for producing a drug-free interval prior to the administration of drug from the compartment; (4) a second composition in the compartment comprising a dose amount of a drug for producing a therapeutic effect, said drug a member selected from the group consisting of verapamil, nimodipine, nitredipine, nisoldipine, nicardipine, felodipine, diltiazem, lidoflazine, tiapamil, guanabenz, isradipine, gallopamil, amlodipine, mioflazine, caroverene, diltiazem hydrochloride, and midazolam; (5) a third composition in the compartment that expands in the presence of fluid that enters the device; and, (6) exit means in the wall for connecting the exterior of the device with the compartment; (b) imbibing fluid into the compartment thereby causing the third composition to expand and push against the second composition; and (c) administering the second composition comprising the drug after the first drug-free composition is released from the device. 2. A method for administering a drug to the gastrointestinal tract of a warm-blooded animal according to claim 1, wherein a dose amount of drug is administered from the exterior of the osmotic device. 3. A method for administering a drug to the gastrointestinal tract of a warm-blooded animal, which method comprises: (a) admitting an osmotic device into the gastrointestinal tract of the warm-blooded animal, said device comprising: (1) a compartment; (2) a wall that surrounds and forms the compartment, said wall comprising a composition that is permeable to the passage of fluid; (3) a first composition in the compartment, said first composition drug-free for producing a drug-free interval prior to the administration of drug from the compartment; (4) a second composition in the compartment comprising a dose amount of a drug for producing a therapeutic effect, said drug a member selected from the group consisting of drugs that act on peripheral nerves, adrenergic receptors, cholinergic receptors, nervous system, skeletal muscles, cardiovascular system, smooth muscles, blood circulatory system, synaptic sites, neuroeffector junctional sites, endocrine system, hormone systems, immunological system, reproductive system, skeletal system, autacoid systems, alimentary systems, excretory systems, inhibitory of autocoid systems, inhibitory of autocoids and histamine systems of the warm-blooded animal; (5) a third composition in the compartment that expands in the presence of fluid that enters the device; and, (6) exit means in the wall for connecting the exterior of the device with the compartment; (b) imbibing fluid into the compartment thereby causing the third composition to expand and push against the second composition; and (c) administering the second composition comprising the drug after the first drug-free composition is released from the device. 4. A method for administering a drug to the gastrointestinal tract of a warm-blooded animal according to claim 3, wherein the drug is a member selected from the group consisting of anticonvulsants, analgesics, anti-Parkinsons, anti-inflammatories, calcium antagonists, anesthetics, antimicrobials, antimalarials, antiparasites, antihypertensives, antihistamines, antipyretics, alpha-adrenergic agonist, alpha-blockers, biocides, bactericides, bronchial dilators, beta-adrenergic blocking drugs, contraceptives, cardiovascular drugs, calcium channel inhibitors, depressants, diagnostics, diuretics, electrolytes, hypnotics, hormonals, hyperglycemics, muscle contractants, muscle relaxants, ophthalmics, psychic energizers, parasympathomimetics, sedatives, sympathomimetics, tranquilizers, urinary tract drugs, vaginal drugs, viricides, vitamins, nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, and polypeptide therapeutic activities. 5. A method for administering a dose of a drug at least once a day from a dosage form to the gastrointestinal tract of a warm-blooded animal, which method comprises: (a) admitting the dosage form into the gastrointestinal tract of the warm-blooded animal, said dosage form comprising: (1) a compartment; (2) a wall that surrounds and forms the compartment, said wall comprising a composition that is permeable to the passage of fluid; (3) a first composition in the compartment comprising a polymer comprising a 9,000 to 10,000,000 molecular weight, said first composition drug-free for producing a drug-free interval prior to the administration of drug from the compartment; (4) a second composition in the compartment comprising a dose amount of a drug for producing a therapeutic effect, said drug consisting of a member selected from the group consisting of an anticonvulsant, analgesic, anti-Parkinson, anti-inflammatory, anesthetic, antimicrobial, antimalarial, antiparasite, antihypertensive, antihistamine, antipyretic, alpha-adrenergic agonist, alpha-blocker, biocide, bactericide, bronchial dilator, beta-adrenergic blocking drug, contraceptive, cardiovascular drug, calcium channel inhibitor, depressant, diagnostic, diuretic, electrolyte, hypnotic, hormone, hyperglycemic, muscle contractant, muscle relaxant, ophthalmic, psychic energizer, parasympathomimetic, sedative, sympathomimetic, tranquilizer, urinary, vaginal, viricide, vitamin, nonsteroidal anti-inflammatory, angiotensin converting enzyme inhibitors, polypeptide, proteins, sleep inducer, and anorexia therapeutically active drugs; (5) a third composition in the compartment that expands in the presence of fluid that enters the dosage form; (6) exit means in the wall for connecting the exterior of the dosage form with the compartment; and, (b) imbibing fluid into the compartment causing the third composition to expand and push against the second composition; and thereby (c) administering the dose of drug from the drug composition after at least some of the first drug-free composition is released from the compartment. 6. A method for administering a dose of verapamil at least once a day from a dosage form to the gastrointestinal tract of a warm-blooded animal, which method comprises: (a) admitting the dosage form into the gastrointestinal tract of the warm-blooded animal, said dosage form comprising: (1) a compartment; (2) a wall that surrounds and forms the compartment, said wall comprising a composition that is permeable to the passage of fluid; (3) a first composition in the compartment, said first composition drug-free for producing a drug-free interval prior to the administration of verapamil from the compartment; (4) a second composition in the compartment comprising a dose amount of 0.05 ng to 1.5 g of verapamil for producing a therapeutic effect; (5) a third composition in the compartment that expands in the presence of fluid that enters the dosage form; (6) exit means in the wall for connecting the exterior of the dosage form with the compartment; and, (b) imbibing fluid into the compartment causing the third composition to expand and push against the second composition; and thereby (c) administering the verapamil after the first drug-free composition is released from the dosage form. 7. A method for administering a dose of drug at least one a day from a dosage form to the gastrointestinal tract of a warm-blooded animal according to claim 6, wherein (7) a substantially immediate release dose amount of drug is on the exterior surface of the wall; and, (d) administering the dose of drug from the exterior wall by contacting the drug with gastrointestinal fluid. 8. A method for administering a drug to the gastrointestinal tract of a warm-blooded animal, which method comprises: (a) admitting an osmotic device into the gastrointestinal tract of the warm-blooded animal, said device comprising: (1) a compartment; (2) a wall that surrounds and forms the compartment, said wall comprising a composition that is permeable to the passage of fluid; (3) a first composition in the compartment comprising a viscosity of 100 centipoises to 10,000,000, said first composition drug-free for producing a drug-free interval prior to the administration of drug from the compartment; (4) a second composition in the compartment comprising a dose amount of a drug for producing a therapeutic effect, said drug a member selected from the group consisting of amyl nitrate, glyceryl trinitrate, octyl nitrite, sodium nitrite, erythrityl tetranitrate, isosorbide dinitrate, mannitol hexanitrate, pentaerythritol tetranitrate, pentritol, triethanolamine trinitrate, and trolnitrate phosphate; (5) a third composition in the compartment that expands in the presence of fluid that enters the device; and, (6) exit means in the wall for connecting the exterior of the device with the compartment; (b) imbibing fluid into the compartment thereby causing the third composition to expand and push against the second composition; and (c) administering the second composition comprising the drug after the first drug-free composition is released from the device.