Method for administering drug

• US 5,348,746 A
• Filed: 10/21/1992
• Issued: 09/20/1994
• Est. Priority Date: 12/06/1991
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Burkoth, Terry L., Dong, Liang C., Wong, Patrick S. L., Barclay, Brian L., Childers, Jerry D., Dealey, Michael H.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Kulkosky, Peter F.
• Application Number:
  US07/964,538
• Time in Patent Office: 699 Days
• Field of Search: 424/435, 424/78.08, 424/422, 424/425, 424/434, 424/472, 424/473, 128/260
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

A dosage form is disclosed comprising means for lessening the tackiness and/or irritation of the components of the dosage form to mucosal tissue. The dosage form provides means for forming in the dosage form a floc comprising a drug, which floc, when delivered from the dosage form, lessens the tackiness and/or irritation of the mucosal tissue of a warm-blooded recipient.

Claims

1. A method for administering a drug to a patient in need of drug therapy, wherein the method comprises:

(a) admitting into the patient a dosage form comprising;

(1) a wall comprising at least in part a composition permeable to the passage of fluid, which wall surrounds;

(2) a compartment;

(3) a drug layer in the compartment comprising 10 ng to 1200 mg of drug, a hydrophilic polymer that exhibits a lower critical solution temperature below the temperature of the patient, and a dehydrating agent that exhibits an affinity for fluid present in the patient;

(4) a hydrogel push layer in the compartment that absorbs fluid, expands and thereby displaces the first composition from the dosage form;

(5) at least one passageway in the wall that connects the exterior with the interior of the dosage form for delivering the drug from the dosage form;

(b) imbibing fluid into the dosage form causing the hydrophilic polymer to precipitate in situ above the lower critical solution temperature in the presence of the dehydrating agent, which precipitate comprises the drug; and

,

(c) administering the drug to the patient by the push layer pushing the drug precipitated from the dosage form.

2. A method for administering a drug to a patient in need of drug therapy, wherein the method comprises:

(a) admitting into the patient a dosage form comprising;

(1) a wall comprising at least in part a composition permeable to the passage of fluid, which wall surrounds;

(2) a compartment;

(3) a push layer in the compartment that absorbs fluid, expands and thereby displaces the first composition from the dosage form;

(4) at least one passageway in the wall that connects the exterior with the interior of the dosage form for delivering the drug from the dosage form;

(5) a first layer in the compartment comprising 10 ng to 1200 ng of drug, a hydrophilic polymer that exhibits a critical solution temperature which is a means for providing a pricipitate in situ, and a dehydrating agent that exhibits an affinity for water and can depress the critical solution temperature of the hydrophilic polymer; and

wherein the dosage form is characterized by;

(b) causing the hydrophilic polymer to precipitate in situ above the critical solution temperature in the presence of the dehydrating agent and in the preserve of fluid imbibed into the dosage form, which precipitate comprises the drug; and

thereby,

(c) administering the drug to the patient by the push layer pushing the drug precipitated from the dosage form.

3. A method for administering an anti-fungal drug to the buccal area of a patient in need of anti-fungal therapy, wherein the method comprises:

(a) admitting to the patient a dosage form comprising;

(1) a wall comprising a semipermeable composition permeable to the passage of fluid, which wall defines;

(2) a compartment;

(3) a drug composition in the compartment comprising 10 ng to 1200 mg of the anti-fungal nystatin drug, a hydrophilic polymer that possesses a critical solution temperature that corresponds to the temperature of the patient, and a dehydrating agent;

(4) a hydrogel push composition comprises a hydrogel that absorbs fluid, expands and thereby pushes the drug composition from the dosage form;

(5) at least one passageway in the wall that connects the exterior with the interior of the dosage form for delivering the drug from the dosage form;

(b) imbibing fluid into the dosage form; and

wherein the method is characterized by;

(c) causing (i) the hydrophilic polymer to precipitate in situ above the critical solution temperature in the presence of the dehydrating agent and in the presence of imbibed fluid, thereby providing a floc comprising the drug and also causing (ii) the push layer to absorb fluid and expand; and

,

(d) administering the anti-fungal nystatin to the buccal area by the push composition pushing the floc from the dosage form.

4. The method for administering the anti-fungal drug to the buccal area of a patient according to claim 3, wherein nystatin is replaced with a drug selected from the group consisting of amphotericin, flucytosine, ketoconazole, miconazole, itraconazole, fluconazole, griseofulvin, clotrimazole, econazole, butoconazole, ciclopirox olamine, haloprogin, tolnaftate, and naftifine.

5. The method for administering the anti-fungal drug to the buccal area of a patient according to claim 3, wherein the hydrogel is kappa-carrageenan.

6. The method for administering the anti-fungal drug to the buccal area of a patient according to claim 3, wherein the dehydrating agent is mannitol.

7. A method for treating a fungal infection in an immunocomprised patient, wherein the method comprises:

(a) admitting into the oral cavity of an immunocomprised patient having a fungal infection a dosage form comprising;

(1) a wall that defines the dosage form which is shaped and adapted for admittance into the oral cavity, the wall comprising a semipermeable composition permeable to the passage of fluid, which wall surrounds;

(2) an internal compartment comprising;

(i) 10 ng to 1200 mg of an anti-fungal drug, a hydrophilic polymer comprising a critical solution temperature of 35°

C. to 50°

C., and a dehydrating agent that exhibits an affinity for fluid imbibed into the compartment; and

, (ii) a hydrogel that absorbs fluid that enters the compartment and thereby expand and pushes the drug from the compartment;

(3) an exit port in the wall that connects the exterior with the interior of the dosage form for delivering the anti-fungal drug from the dosage form;

(b) imbibing fluid into the dosage form thereby (iii) causing the hydrophilic polymer to precipitate in situ above its critical solution temperature to form a precipitate composition comprising the anti-fungal drug, and (iv) causing the hydrogel to absorb fluid and push the precipitate-drug composition from the dosage form;

whereby

(c) an anti-fungal drug is administered to the patient for treating the fungal infection.

8. The method for treating a fungal infection in an immunocomprised patient according to claim 7, wherein the hydrophilic polymer comprises a lower critical solution temperature of 35°

C. to 50°

C.

9. The method for treating a fungal infection in an immunocomprised patient according to claim 7, wherein the oral cavity comprises buccal mucosa.

10. The method for treating a fungal infection in an immunocomprised patient according to claim 7, wherein the oral cavity comprises sublingual tissue.

11. The method for treating a fungal infection in an immunocomprised patient according to claim 7, wherein the fungal infection comprises yeast-like fungi.

12. The method for treating a fungal infection in an immunocomprised patient according to claim 7, wherein the fungal infection is associated with ulceration, perforations and fungemia of the oral cavity.