Antiviral therapy

• US 5,358,721 A
• Filed: 12/04/1992
• Issued: 10/25/1994
• Est. Priority Date: 12/04/1992
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Kuczynski, Anthony L., Kidney, David J., Wong, Patrick S. L., Guittard, George V.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): VENKAT, JYOTHSNA A
• Application Number:
  US07/985,989
• Time in Patent Office: 690 Days
• Field of Search: 424/473, 424/468, 604/891.1
• 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 for administering an antiviral drug to a patient in need of antiviral therapy.

Claims

1. A method for administering an antiviral drug to the gastrointestinal tract of a human in need of antiviral therapy, wherein the method comprises:

(a) admitting a dosage form orally into the gastrointestinal tract of the human, said dosage form comprising;

(1) a semipermeable wall permeable to the passage of fluid and substantially impermeable to the passage of an antiviral drug, said wall comprising a member selected from the group consisting of a cellulose acylate, cellulose diacylate, and cellulose triacylate, which wall surrounds;

(2) a compartment comprising 0.05 ng to 200 mg of an antiviral drug and a flux promoter selected from the group consisting of a cationic, anionic, and nonionic promoter for promoting the therapeutic effects of the antiviral drug;

(3) an exit passageway in the wall that connects the gastrointestinal tract with the compartment;

(4) a displacement composition in the compartment;

(b) imbibing gastrointestinal fluid through the semipermeable wall for activating the displacement composition causing the displacement composition to expand and displace the antiviral drug composition from the compartment through the exit passageway, and wherein the method is characterized by;

(c) administering from the compartment the antiviral drug composition comprising the antiviral drug and the flux promoter to the gastrointestinal tract for antiviral therapy.

2. The method for administering the antiviral drug to the gastrointestinal tract of a human according to claim 1, wherein the antiviral drug is a member selected from the group consisting of acyclovir, azidouridine, didanosine, zidovudine, zalcitabine, and dideoxycitidine.

3. A hydro-activated osmotic dosage form for delivering a composition comprising an antiviral drug to a patient in need of antiviral therapy, wherein the dosage form comprises:

(a) a semipermeable wall permeable to the passage of fluid and substantially impermeable to the passage of an antiviral drug, which semipermeable wall comprises a member selected from the group consisting of a cellulose acrylate, cellulose diacylate and cellulose triacylate and surrounds;

(b) a fluid-receiving internal compartment;

(c) exit means in the semipermeable wall that connects the exterior of the dosage form with the internal compartment;

(d) a fluid-activated displacement layer in the compartment for displacing the composition comprising the antiviral drug from the internal compartment; and

wherein the dosage form is characterized by;

(e) a composition layer comprising 0.05 ng to 1000 mg of an antiviral drug 0 to 20 wt % of an antiviral flux promoter and means for mixing with an imbibed aqueous fluid and thereby forming a deliverable composition for delivering the antiviral drug to a patient in need of antiviral therapy.

4. The hydro-activated osmotic dosage form for delivering an antiviral drug composition according to claim 3, wherein the difficult to deliver antiviral drug is poorly soluble in an aqueous fluid.

5. The hydro-activated osmotic dosage form for delivering an antiviral drug composition according to claim 3, wherein the antiviral drug is acyclovir.,

6. The hydro-activated osmotic dosage form for delivering an antiviral drug composition according to claim 3, wherein the antiviral drug is a member selected from the group consisting of azidouridine, didanosine, zidovudine, zalcitabine and dideoxycitidine.

7. The hydro-activated osmotic dosage form for delivering an antiviral drug composition according to claim 3, wherein the antiviral drug flux promoter is a member selected from the group consisting of a cationic, nonionic an anionic promoter.

8. A dosage form for delivering a composition comprising an antiviral drug to a patient in need of antiviral therapy, wherein the dosage form comprises:

(a) a wall permeable to the passage of fluid and substantially impermeable to the passage of an antiviral drug, which wall comprises a member selected from the group consisting of a cellulose acylate, cellulose diacylate and cellulose triacylate; and

wherein the dosage form is characterized by comprising;

(b) a composition comprising 0.05 ng to 1000 mg of an antiviral drug and means for forming with fluid in a patient a composition deliverable by hydro-fluid activity from the dosage form to the patient over time.

9. A composition comprising 0.05 ng to 1200 mg of an antiviral drug;

15 wt % to 40 wt % of a member selected from the group consisting of a polyethylene oxide having a 175,000 to 225,000 molecular weight and a polyethylene oxide having a 275,000 to 325,000 molecular weight; and

0 wt % to 20 wt % of a surface-active agent selected from the group consisting of a cationic, artionic and nonionic agent.

10. The composition comprising the antiviral drug according to claim 9 wherein the antiviral drug is a member selected from the group consisting of acyclovir, azidouridine, anasmycin, amantadine, bromovinyldeoxusidine, chlorovinyldeoxusidine, cytarbine, didanosine, deoxynojirmycin, dideoxycitidine, dideoxyinosine, dideoxvnudeoside, desciclovir, deoxyacyclovir, edoxuidine, enviroxime, fiacitabine, foscarnet, fialuridine, fluorothymidine, fluxuridine, ganciclovir, hypericin, interferon, interlenkin, isethionate, idoxuridine, nevirapine, pentamidine, ribavirin, rimantadine, stavirdine, sargramostin, suramin, trichosanthin, trifluorothymidine, tribromothymidine, trichlorothymidine, vidarabine, zidoviridine, zalcitabine, and 3-azido-3-deoxythymidine.

11. A composition comprising 0.05 ng to 1200 mg of an antiviral drug, a pharmaceutically acceptable cellulose, and a surface-active agent selected from the group consisting of a cationic, artionic and nonionic agent.

12. The composition according to claim 11, wherein the pharmaceutically acceptable cellulose is selected from the group consisting of hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylethylcellulose and hydroxypropylmethylcellulose.

13. The composition according to claim 11, wherein the antiviral drug is indicated for treating a virus infection selected from the group consisting of ovdobial herpes, cutaneous herpes, genital herpes, herpetic proctitis, varicella-zoster herpes, wart herpes, and a virus that replicates by reverse transcription.

14. A method indicated for treating a viral infection, wherein the method comprises admitting orally into the gastrointestinal tract a dosage form comprising a composition that comprises 0.05 ng to 1200 mg of an antiviral drug and a surface-active agent selected from the group consisting of a cationic, anionic, and nonionic agent, which dosage form delivers the composition at a controlled rate over a period of time to the gastrointestinal tract for antiviral therapy.

15. The method indicated for treating a viral infection according to claim 14, wherein the composition comprises a cellulose selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, hydroxypropylethylcellulose, and hydroxyethylcellulose.