Title : Ophthalmic in situ gels with balsam poplar buds extract: formulation, rheological characterisation and quality evaluation
Abstract:
Introduction: Inflammatory eye diseases are one of the most common diseases in contemporary societies. Polyphenolic additives in artificial tears have antioxidative, antibacterial and anti-inflammatory properties, which are important in seeking a positive treatment effect. Poplar buds, same as propolis, are the source of polyphenols [1]. Poplar buds due to their antibacterial, antioxidant and anti-inflammatory action are potential active material in the production of eye drops. Therefore, it is actual to present new data on application of poplar bud extract in the modelling of ophthalmological preparations. The aim of this research is to adapt the balsam poplar bud extract for use in the production of ophthalmic gels in situ and to evaluate their quality by making tests of their chemical composition, rheological properties and biological activity in vitro. Promising results of these tests can serve as a basis for further research.
Methods: Purified water was chosen as the extractant for the extraction of balsam poplar buds. Extraction was performed in an ultrasonic bath. After receiving the aqueous balsam poplar buds extract, the extract was lyophilizated. 1% aqueous solution was prepared from the freeze-dried balsam poplar buds extract powder, which was then used in experimental ophthalmic formulations. The total content of phenolic compounds and flavonoids was determined by spectrofotometrical methods. The identification of the predominant active compounds performed by high performance liquid chromatography – HPLC. Poloxamer 407, Hydroxypropyl Methylcellulose (HPMC), Propane-1,2-diol, purified water and a 1% solution were used to form the experimental in situ gels. In situ gels physical characterisations were evaluated by pH-meter and viscosimeter. Antioxidant activity evaluaterd by ABTS and FRAP methods. A rabbit corneal cell line (SIRC) was used to evaluate the irritation of in situ gels. Results were expressed as the mean and standard deviation of three measurements. Results considered as statistically significant at p<0.05.
Results: The research confirmed that lyophilization was an effective method. P-coumaric acid dominates in poplar buds extracts. The formulations with poplar bud extract had pH from 6.07 to 6.7. The data of research showed that viscosity of the produced gels was varying from 11.3 to 170.8 mPa·s. The total phenolic compounds content of in situ gels was in the range of 94.81-98.37% from the theoretical amount of phenolic compounds. The results of antioxidative activity test showed, that the gels produced with poplar bud extract had antioxidant activity. The results of the research showed that the release of phenolic compounds from in situ gels formulations directly depended on the concentration of gelifying polymers. After 5 and 30 minutes exposition and incubation time, which is counted as drug contact with the eye, all tested gels did not have irritating effect on SIRC cell viability.
Conclusions: The results of the research showed that the extract of Populus balsamifera buds is rich in polyphenols, of which p-coumaric acid predominates. The results of this study indicate that the polymers combinations will be expected to be an excellent polyphenols carrier for the prolonged delivery to the surface of the eye.
