Claims for Patent: 6,620,435

Summary for Patent: 6,620,435

Title:	Compositions for topical application of therapeutic agents
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.
Inventor(s):	Osborne; David W. (The Woodlands, TX)
Assignee:	ViroTex Corporation (The Woodlands, TX)
Application Number:	09/236,909
Patent Claims:	1. A dermatological composition comprising: a semisolid aqueous gel; a pharmaceutical dissolved in said gel, wherein said dissolved pharmaceutical crosses the stratum corneum layer of the epidermis and becomes available systemically; and a microparticulate pharmaceutical dispersed in said gel, wherein said microparticulate pharmaceutical does not cross the stratum corneum of the epidermis in its microparticulate state, and wherein the ratio of said microparticulate to dissolved pharmaceutical is at least 5:1. 2. The composition of claim 1, wherein said gel comprises carbomer, hydroxyethylcellulose, hydroxypropylcellulose, cellulose gum, methylvinyl ether/maleic anhydride (MVE/MA) decadiene crosspolymer, or polyvinylmethyl ether/maleic acid (PVM/MA) copolymer. 3. The composition of claim 1, wherein said gel comprises a cross-linked acrylic acid polymer dissolved in an aqueous phase and a caustic material. 4. The composition of claim 1, wherein said microparticulate pharmaceutical is a crystalline precipitant. 5. The composition of claim 1, wherein said microparticulate pharmaceutical is an amorphous precipitant. 6. The composition of claim 1, wherein said dissolved pharmaceutical and microparticulate pharmaceutical comprise an antimicrobial agent, anti-inflammatory agent, antiviral agent, local anesthetic, corticosteroid, destructive therapy agent, antifungal agent, or antiandrogen agent. 7. The composition of claim 1, wherein said microparticulate pharmaceutical and dissolved pharmaceutical comprise different pharmaceuticals. 8. A dermatological composition, comprising a semisolid aqueous gel having about 0.5% to 4.0% carbomer; about 0.5% to 10% pharmaceutical, wherein said pharmaceutical comprises a dissolved pharmaceutical having the capacity to cross the stratum corneum of the epidermis and become systemically available and a microparticulate pharmaceutical that does not cross the stratum corneum of the epidermis in its microparticulate state; and an amine base, sodium hydroxide solution, or potassium hydroxide solution, and wherein the ratio of said microparticulate to dissolved pharmaceutical is at least 5:1. 9. The dermatological composition of claim 8, wherein said dissolved pharmaceutical and said microparticulate pharmaceutical comprise dapsone. 10. The composition of claim 8 wherein said pharmaceutical comprises an antimicrobial agent, antiviral agent, anti-inflammatory agent, local anesthetic, corticosteroid, destructive therapy agent, antifungal agent, or antiandrogen agent. 11. A dermatological gel composition for the treatment of herpes lesions comprising: a semisolid aqueous gel; a first pharmaceutical in said gel, partially in a microparticulate form and partially in a dissolved form, wherein said first pharmaceutical provides optimized delivery for early state lesions when dissolved and optimized delivery for later state lesions when present as a microparticulate; and wherein the ratio of said microparticulate to dissolved first pharmaceutical is at least 5:1 and a second pharmaceutical dissolved in said gel, wherein said second pharmaceutical provides benefit throughout lesion progression. 12. The composition of claim 11, wherein said first pharmaceutical comprises a nucleoside analogue selected from the group consisting of acyclovir, penciclovir, famciclovir, valacyclovir, and ganciclovir, and said second pharmaceutical comprises a local anesthetic selected from the group consisting of tetracaine, tetracaine HCl, dyclonine, dyclonine HCl, dibucaine, and dibucaine HCl. 13. The composition of claim 12, wherein said acyclovir comprises 5% by weight of the composition. 14. The composition of claim 12, wherein said tetracaine HCl comprises 5% by weight of the composition. 15. A dermatological composition, comprising a semisolid aqueous gel having about 0.5% to 4.0% carbomer; about 0.5% to 10% dapsone, wherein said dapsone is dissolved and has the capacity to cross the stratum corneum of the epidermis an become systemically available and a microparticulate pharmaceutical lacking the ability to cross the stratum corneum of the epidermis in its microparticulate state; and an amine base, sodium hydroxide solution, or potassium hydroxide solution.