Ocular delivery of drugs

Abstract

The present invention relates to an aqueous composition comprising a macrolide immunosuppressant drug at a concentration of less than 2% w / v and an amphiphilic carbohydrate compound having a molecular weight in the range 1-50 kDa, for use in treatment of an eye disorder by topical application to the eye, wherein the amphiphilic carbohydrate compound is present at a concentration below 10% w / v of the composition. A preferred carbohydrate compound is quaternary ammonium palmitoyl glycol chitosan (GCPQ). Pharmaceutical compositions and methods of treatment are also provided. The treatment may be for instance dry eye syndromes (DES), vernal keratoconjunctivitis (VKC), eczema, atopic keratoconjunctivitis (AKC), Sjögren syndrome, post-operative refractive surgery, corneal transplant or contact lens intolerance.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a new system for the ocular delivery of drugs.BACKGROUND TO THE INVENTION[0002]Topical ophthalmic formulations are generally used to treat diseases affecting the anterior portion of the eye including but not limited to glaucoma, iritis, conjunctivitis eye infection and dry-eye syndrome (DES). DES refers to a spectrum of ocular surface disorders having various aetiologies and is characterized by chronic eye dryness of the cornea and conjunctiva caused by the improper balance of tear production and drainage or an abnormality in the tear composition. In addition, inflammation of the ocular surface often occurs.[0003]A T-cell lymphocytes mediated inflammatory response has been recognized as a possible cause for DES. As a result, the use of Cyclosporine (CSA) and Tacrolimus (TAC) as topical immunosuppressants have emerged in recent years for the treatment of DES. Such treatments have been shown to decrease inflammatory response...

AI Technical Summary

Benefits of technology

[0037]It is the aim of this invention to provide ophthalmic compositions having good stability, tolerability and bioavailability properties. This is achieved through the use of positively charged amphiphilic self-assembling polymers which are capable of self-assembling in aqueous media. These polymers have multifunctional properties which make them suitable for ophthalmic compositions. They form viscous or non-viscous aqueous dispersions in the form of positively charged nanoparticulate drug carriers which possess muco-adhesive properties. The simplicity of the formulation is maintained as just one excipient can be used. Notably, the use of lipids or emulsions is not required.

[0038]The molecular weight of the polymer molecules is important, as below 1 kDa they will generally be too small to encapsulate sufficient levels of drug, and above 50 kDa, the polymer may result in a composition which is too viscous. An appropriate polymer concentration is also important, and should be below 10% w / v of the composition, to prevent gel formation. Furthermore, having a drug concentration below 2% w / v enables complete incorporation within the polymer molecules.

Problems solved by technology

In addition, inflammation of the ocular surface often occurs.

Due to the hydrophobicity and low aqueous solubility of CSA and TAC, they are generally formulated using oily vehicles which have been linked with bioavailability limitations, stability and ocular tolerance issues.

However, it is known that RESTASIS® is not optimal and the formulation suffers from low ocular bioavailability.

As a result, these compositions are prone to droplet coalescence which limit their shelf life.

In this respect, the release of CSA from the oily vehicles (castor oil emulsion or solution) was limited by the high partition coefficient of CSA in the oily phase.

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