Formulation and Stability of Ataluren Eye Drop Oily Solution for Aniridia

Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, corneal limbal insufficiency, glaucoma, cataract, optic nerve, and foveal hypoplasia. Ataluren eye drops aim to restore ocular surface PAX6 haploinsufficiency in aniridia-related keratopathy (ARK). However, there are currently no available forms of the ophthalmic solution. The objective of this study was to assess the physicochemical and microbiological stability of ataluren 1% eye drop in preservative-free low-density polyethylene (LDPE) bottle with an innovative insert that maintains sterility after opening. Because ataluren is a strongly lipophilic compound, the formulation is complex and involves a strategy based on co-solvents in an aqueous phase or an oily formulation capable of totally dissolving the active ingredient. The visual aspect, ataluren quantification by a stability-indicating chromatographic method, and microbiological sterility were analyzed. The oily formulation in castor oil and DMSO (10%) better protects ataluren hydrolysis and oxidative degradation and permits its complete solubilization. Throughout the 60 days period, the oily solution in the LDPE bottle remained clear without any precipitation or color modification, and no drug loss and no microbial development were detected. The demonstrated physical and microbiological stability of ataluren 1% eye drop formulation at 22–25 °C might facilitate clinical research in aniridia.

Selection of the optimal composition of vegetable oil and chlorophyllipt oil components

Investigate the antimicrobial properties of various concentrations of vegetable essential oils in combination with an oil solution of chlorophyllipt as possible ingredients for ointments for wounds. Microbiological tests were performed according to standard methods using E. coli test cultures, S. aureus, Str. agalactiae and P. fluorescens. The results of studies of antibacterial activity of both individual ingredients and their combinations are presented, namely: 4 % essential oil of Siberian pine, 2 % essential oil of eucalyptus, 1.5 % essential oil of cloves, 1.5 % of essential oil of cedar, 2.0 % tea tree essential oil and 1.0 % chlorophyllipt oil solution. Bacteria, which are usually typical agents of wound infections, have been found to be quite sensitive to the drugs tested. High activity of essential oils and oily solution of chlorophyllipt with respect to E. coli and S. aureus was revealed. In particular, a 1.0 % oily solution of chlorophyllipt caused staphylococcal growth retardation zones whose diameters were 1.4 times larger than the antibiotic clindamycin. It was determined that representatives of gram-negative microflora were more sensitive to the investigated essential oils and chlorophyll. The optimal composition of the experimental drug called “Ointment for wounds” is offered. The results of preclinical testing showed a sufficiently high efficiency compared to traditional means. The results obtained with regard to antimicrobial activity indicate the prospect of using preparations based on the essential oil of Siberian pine, eucalyptus, carnation, cedar, tea tree and oil solution of chlorophyllipt for the treatment of skin diseases in animals. This data will help to develop new effective and safe veterinary treatments for wound care.

PREPARATION AND CHARACTERIZATION OF SUPERHYDROPHILIC NANOCOMPOSITE ULTRAFILTRATION MEMBRANES FOR TREATMENT OF HIGHLY CONCENTRATED OIL-IN-WATER EMULSION

In oily wastewater treatment using membrane technology, surface fouling is the major issue that could deteriorate membrane flux and shorten its lifespan. Therefore, nanocomposite membranes were developed in this study by incorporating titanium dioxide (TiO2) and hydrous manganese oxide (HMO) nanoparticles into polymeric membrane matrix. Three different types of membranes were fabricated. They were pristine PES and membrane incorporated with TiO2 or HMO. With respect to pure water flux, TiO2- and HMO-incorporated membranes showed value of 57 and 40 L/m2.h, respectively. These values were 33-90% higher than that of control PES membrane. In treating 500 ppm oily solution, TiO2 membrane exhibited the highest water flux. However, the membrane’s oil removal rate was slightly compromised. When tested with higher concentration of oily solution (5,000 or 10,000 ppm), TiO2- and HMO-incorporated membranes still showed promising water flux with 94.5-99.6% oil removal rate. This proved that ultrafiltration membrane incorporated with suitable nanomaterials could improve the water flux of pristine PES membrane and is of more practical for industrial applications.

ФАРМАКО–ТОКСИКОЛОГІЧНА ОЦІНКА ПРЕПАРАТУ «ЦИФЛУР»

The results of pharmaco–toxicological evaluation insectoacaricid preparation «Tsiflur», in particular the study of locally irritating effect of the drug on the skin and mucous membranes of rabbits eyes. The preparation «Tsiflur» – representative of synth pyrethroids, in its composition has the active ingredient cyfluthrin, production NPF «Brovafarma». According to the manufacturer's instructions, the preparation recommended for the control of flying midges and other representatives akaroentomofauny that have veterinary importance. The tool is a clear oily solution of a yellowish color.Experimental studies were conducted on rabbits analogues in several stages. In the first phase we studied local irritant effect of the preparation in varying degrees of dilution when applied to intact skin of rabbits. The aim of the second stage of the research was to determine the local irritant effect of the d preparation on the mucous membrane of the eyes of rabbits.It has been established that the preparation «Tsiflur» in the test concentration (1: 100, 1: 200, 1: 400 concentrate solution) during the observation period did not show locally irritating effects in a single application to the intact areas of the skin of rabbits. Monitoring the bellies of the experiment showed no redness, swelling, thickening of the skin folds and the pain response to palpation place application of the preparation. Not set also signs of toxic effects of native preparation «Tsiflur», when applied under similar conditions. The reaction of the skin of animals per application experimental preparation was valued at 0 points. In the study of the preparation in a similar concentration on the possibility of providing local irritant effect on the mucous membrane of the eyes of rabbits determined that the native application of the preparation led to the emergence of a slight reddening of the eye mucosa and the appearance of watery eyes. These symptoms disappear without any intervention on the second day of the experiment. The reaction to the introduction of the preparation «Tsiflur» was estimated at 1 point, for each identified symptom.