Methods and compositions for sustained delivery of drugs

Abstract

The present disclosure relates to methods and compositions for the topical sustained delivery of therapeutic agents. Topical application of compositions containing a muscle fasciculating agent result in the sustained release of any therapeutic agent contained within the composition. More particularly, topical application of such compositions to the outer surface of the eyelid of a patient results in increased absorption and sustained release of the therapeutic agent into the eyes or systemically.

Description

CROSS-REFERENCE OF RELATED APPLICATION[0001]This application claims priority to provisional application, U.S. Application No. 61 / 256,614, filed Oct. 30, 2009 and U.S. Application Ser. No. 61 / 289,471, filed Dec. 23, 2009, both of which are incorporated herein by reference thereto.TECHNICAL FIELD[0002]The present invention relates generally to methods and compositions for the controlled topical delivery of drugs. More specifically, the present invention relates to methods and compositions for delivery of one or more drugs to the eye, a specified area of the eye or systemically to a remote target by topical application to at least one upper eyelid and optionally at least one lower eyelid. More specifically, these methods comprise applying a preparation containing the desired drug or combination of drugs to the surface of at least one upper eyelid and optionally at least one lower eyelid, thereby causing transfer of the drug or drugs from the eyelid into the eye or systemic circulation ...

AI Technical Summary

Benefits of technology

"The patent describes a method and composition for delivering drugs or other therapeutic agents to the eyeball and eyelid through the application of a composition to the eyelid. The composition can contain a muscle fasciculation agent, such as caffeine or theophylline, in an amount of up to 1% of the composition. The method can also involve applying two different drugs to different areas of the eyelid to enhance uptake. The composition can be used to treat glaucoma, dry eye, or other eye diseases or conditions. The technical effect of the invention is to provide a more effective and targeted method for delivering drugs to the eye for therapeutic purposes."

Problems solved by technology

Although some unintended drug absorption may occur, it is in sub-therapeutic quantities and generally of minor concern.

Thus, transdermal systemic delivery of drugs is limited by the poor permeability of some drugs through the skin and limitations of size of drugs that can diffuse through the skin barrier, i.e., less than 500 Daltons.

Moreover, because only limited amounts of drugs actually penetrate the skin layers even when penetration enhancers are applied, this route of administration can only be used for drugs that require very small plasma concentration to be effective.

Topical administration of drugs to the eye for local delivery has been used successfully for years, e.g., eye drops for application directly to the eye or percutaneously absorptive compositions for passive diffusion across the skin or upper and / or lower eyelid, however, topical drug delivery for treatment of the posterior segments of the eye poses several problems.

The posterior segments of the eye are exquisitely protected from the external environment, which poses unique and fairly challenging hurdles for drug delivery.

Even lipophilic molecules applied to the eye, for example in the form of eye drops, wash over the conjunctiva quickly, resulting in a true contact time of about ninety seconds or less, which is not enough time to permit large quantities to pass through the conjunctiva.

It is somewhat dogmatic that topical ocular delivery is insufficient to achieve therapeutic drug levels in the posterior segments.

Inclusion of a vasoconstrictor in certain ophthalmic compositions, particularly those intended to treat glaucoma, for example, has significant drawbacks since the vasoconstrictor restricts blood flow in the immediate area of the eye as well as within the eye, thereby exacerbating the underlying condition.

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