Compositions and methods for topical application of therapeutic agents

• US 6,060,085 A
• Filed: 11/30/1998
• Issued: 05/09/2000
• Est. Priority Date: 09/11/1996
• Status: Expired due to Term

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: David W. Osborne
• Inventors: Osborne, David W.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/201,521
• Time in Patent Office: 526 Days
• Field of Search: 424/484-488, 514/859, 514/944, 252/315.01, 252/315.07
• US Class Current: 424/484
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals

Abstract

The present invention generally relates to pharmaceutical compositions that enable control of drug delivery properties and the development of optimal drug delivery strategies customized for particular drugs and particular diseases. The composition includes a dissolved pharmaceutical that has the capacity to permeate the stratum corneum layer of the epidermis and become available systemically, and a pharmaceutical in a microparticulate state that does not readily cross the stratum corneum of the epidermis. The dissolved and microparticulate pharmaceuticals may be the same or different pharmaceuticals. Methods for the preparation and use of the compositions are also provided. In a preferred embodiment, the invention finds particular use in a formulation for the topical application of dapsone for the treatment of acne. In another preferred embodiment, the invention finds particular use for the treatment of herpes lesions.

Claims

1. A method for the treatment of dermatological conditions comprising applying topically a semisolid gel composition, the semisolid gel composition comprising:

a semisolid aqueous gel;

a first pharmaceutical partially in a microparticulate form and partially dissolved in said semisolid aqueous gel; and

a second pharmaceutical dissolved in said semisolid aqueous gel;

wherein;

the first pharmaceutical provides optimized delivery for early state lesions when dissolved and optimized delivery for later state lesions when present as a microparticulate; and

said second pharmaceutical provides benefit throughout lesion progression.

2. The method of claim 1, wherein:

the first pharmaceutical comprises an antimicrobial agent, anti-inflammatory agent, antiviral agent, local anesthetic agent, corticosteroid, destructive therapy agent, antifungal agent, or antiandrogen agent; and

the second pharmaceutical comprises an antimicrobial agent, anti-inflammatory agent, antiviral agent, local anesthetic agent, corticosteroid, destructive therapy agent, antifungal agent, or antiandrogen agent.

3. The method of claim 1, wherein the first pharmaceutical is dapsone.

4. The method of claim 1, wherein the second pharmaceutical is dapsone.

5. The method of claim 1, wherein:

the first pharmaceutical is dapsone; and

the second pharmaceutical is dapsone.

6. A method for treating disease comprising applying topically an aqueous gel composition comprising a dissolved pharmaceutical and a microparticulate pharmaceutical;

wherein;

the dissolved pharmaceutical crosses the stratum corneum of the epidermis to become systemically available; and

the microparticulate pharmaceutical minimally crosses the stratum corneum in its microparticulate state.

7. The method of claim 6, wherein the aqueous gel composition comprises between about 1.0% (w/w) and about 10% (w/w) antiviral agent.

8. The method of claim 6, wherein the aqueous gel composition comprises between about 0.5% (w/w) and about 10% (w/w) antiandrogen.

9. A method for treating acne comprising topically applying a gel composition comprising a dissolved anti-inflammatory pharmaceutical and a microparticulate antimicrobial pharmaceutical, wherein:

the dissolved anti-inflammatory pharmaceutical crosses the stratum corneum of the epidermis and is absorbed into the lower two-thirds of the pilosebaceous unit; and

the microparticulate antimicrobial pharmaceutical is primarily delivered into the upper third of the pilosebaceous unit, crossing the stratum corneum of the epidermis only minimally.

10. The method of claim 9, wherein:

the dissolved anti-inflammatory pharmaceutical is dapsone; and

the microparticulate antimicrobial pharmaceutical is dapsone.

11. A method for preparing a dermatological gel composition, comprising:

dissolving methylparaben and propylparaben in a solvent to form a solution;

dissolving a pharmaceutical in the solution to form a pharmaceutical component;

contacting water and a polymer to form a homogeneous dispersion;

contacting the pharmaceutical component and the homogeneous dispersion to form a pharmaceutical dispersion; and

contacting the pharmaceutical dispersion and a caustic material to form a dermatological gel composition;

wherein;

the solvent is ethoxydiglycol or 1-methyl-2-pyrrolidone; and

the dermatological gel composition comprises dissolved pharmaceutical and microparticulate pharmaceutical.

12. The method of claim 11, wherein the pharmaceutical is acyclovir, tetracaine, tetracaine hydrochloride, or a combination thereof.

13. The method of claim 11, wherein the pharmaceutical is dapsone.

14. A method for preparing a dermatological gel composition, comprising:

dissolving methylparaben and propylparaben in a solvent to form a solution;

dissolving a pharmaceutical in the solution to form a pharmaceutical component;

contacting water and the pharmaceutical component to form a first pharmaceutical dispersion;

contacting the first pharmaceutical dispersion and a polymer to form a second pharmaceutical dispersion; and

contacting the second pharmaceutical dispersion and a caustic material to form a dermatological gel composition;

wherein;

the solvent is ethoxydiglycol or 1-methyl-2-pyrrolidone; and

the dermatological gel composition comprises dissolved pharmaceutical and microparticulate pharmaceutical.

15. The method of claim 14, wherein the pharmaceutical is acyclovir, tetracaine, tetracaine hydrochloride, or a combination thereof.

16. The method of claim 14, wherein the pharmaceutical is dapsone.