DEVELOPMENT OF SUSTAIN RELEASE POVIDONE IODINE OPHTHALMIC DROP THROUGH NOVEL IN-SITU GEL FORMULATION

G. Wei, X. Gao, X. Li, Y. Lu, J.J. Baldwin, B. Liang
IVIEW Therapeutics Inc.,
United States

Keywords: povidone iodine, in situ gel, sustain release, viral conjunctivitis, ophthalmic, adenovirus, drug delivery

Summary:

Acute conjunctivitis (“pink eye”) is one of the most common and most contagious ocular infections seen in the United States, Japan and Europe. There are 5.9 million cases of infectious conjunctivitis annually in the United States and approximately 5.4 million cases in the EU annually. Approximately 50 percent of infectious conjunctivitis cases have a viral etiology, and 65 to 90 percent of these are caused by adenovirus. Viral conjunctivitis is highly infectious and transmissible, causing lost work and school days as well as increased healthcare costs and risks from unnecessary antibiotic prescriptions. We developed the long-acting povidone iodine (PVP-I) ophthalmic drops for the treatment of active infections of the conjunctiva and cornea by bacteria, mycobacteria, virus, fungus, or amoebic causes. There is currently no broadly effective therapy that treats all causes of infection and nothing is approved for the treatment of viral conjunctivitis. This represents a massive unmet need in ophthalmology. IVIEW-1201 has two distinct features: first, it is effective against both bacteria and viruses and; second, there has been no documented case of resistance. It solves the three biggest problems in the treatment of eye infections: spectrum, resistance and long-acting. Povidone-iodine is a commercially available iodophor routinely used in ophthalmology and general surgery. Povidone-iodine solutions have been proven effective before (5% solution)[1,2] and after ocular surgery (1.25%)[3,4], at birth (2.5%), [5] and for active infections (1.25%).[6] PVP-I is the only agent known to prevent post-op endophthalmitis. Solutions of PVP-I are toxic to viruses (including HIV), fungi, parasites and bacteria with no known development of resistance. It is well described in the literature that aqueous PVP-I solutions exhibit greater antiseptic efficacy at lower concentrations. [7] Furthermore, these lower concentrations are less irritating to the eyes, ears and skin. A 0.6% PVP-I in combination with dexamethasone formulation previously invented by the author is advancing into Phase III clinical trials by Shire in March 2017. [8] However, a sustain release formulation of PVP-I is never been reported due its strong acidity and easily soluble in water. Ophthalmic topical drug delivery is one of the important methods of application, but the existence of cornea barrier, tear dilution and lacrimal passage drainage effect limit the treatments and bioavailability of many topical ophthalmic preparations. An ideal ophthalmic formulation should be administrated in eye drop form, without causing blurred vision or irritation. This problem can be overcome using in situ gel-forming drug delivery systems prepared from polymers that exhibit sol-to-gel phase transitions due to a change in a specific physicochemical parameter in the cul-de-sac. [9] We have developed a novel in-situ gel formulation IVIEW-1201 where the effective concentration of PVP-I is maintained by the equilibrium between solution PVP-I and the gel bound components resulting in a long lasting, less toxic pharmacological effect. [10,11] The project has optimized stable in-situ gel PVP-I formulations that have good gel strength, sustain release properties and are non-irritating to the eye, while they maintain antimicrobial and antiviral properties in both in-vitro and in vivo.