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Maria G Saita, Danilo Aleo, Sergio Mangiafico, Barbara Melilli, Melina G Cro, Sebastiano Mangiafico; INNOVATIVE AQUEOUS AZITHROMYCIN OPHTHALMIC FORMULATION. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5783.
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© ARVO (1962-2015); The Authors (2016-present)
Azithromycin (AZM) is a semi-synthetic macrolide antibiotic largely employed as topical formulation to cure ocular surface infections. Unfortunately, AZM is unstable and practically insoluble in water. In fact, commercial formulations of AZM stable at room temperature are available only in oily vehicle, if a water vehicle is employed the product has to be refrigerated. Our aim was to develop an aqueous mucoadhesive AZM formulation stable at room temperature.
The new formulation of AZM (MDV 1226) was prepared by adding 1.5% of AZM dihydrate, in a solution of appropriate cyclodextrin, to an isosmolar buffer solution (pH=6.7-7.2). The mucoadhesive Hyaluronic Acid was added to improve precorneal residence time of MDV 1226 on the ocular surface. Stability studies were performed under different ICH recommended conditions at 25°C and 40°C. Concentrations (%) of AZM (evaluated by HPLC), pH and Osmolality of the formulation were controlled for 12 months. Moreover a comparative stress thermal study at 70°C was conducted in comparison to commercial topical aqueous formulation of Azithromycin (Azasite).
Stability study conducted at 70°C showed that AZM in MDV 1226 was more stable than AZM in Azasite: after 2 weeks concentration of AZM in the two formulations was 70% in MDV 1226 and only 17% in Azasite. Stability study under ICH recommended conditions showed that AZM in MDV1226 at 25°C was 99% after 12 months and 80% at 40°C after 6 months. The main degradation pattern of AZM was elucidated by HPLC-MS and concerns the hydrolysis of sugar at C-3 (L-Cladinose) of AZM lactone to conduct at descladinose azithromycin (DAZM). Osmolality and pH in MDV 1226 were maintained stable for 12 months.
Stability studies showed that no significant changes were observed with respect to pH, Osmolality and concentration of AZM in MDV 1226 for 12 months at room temperature. The presence of the mucoadhesive Hyaluronic Acid in MDV 1226 should guarantee better performance of the topical AZM. Pharmacokinetics studies in rabbits are on going.
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