Limitations when use chloramphenicol-bcyclodextrins complexes in ophtalmic solutions buffered with boric acid/borax system

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Abstract

Chloramphenicol eye drops are commonly prescribed in concentrations of 0.5-1% in the treatment of infectious conjunctivitis. In terms of ophthalmic solution preparation, the major disadvantage of chloramphenicol consists in its low solubility in water. The solubility is increased by substances that form chloramphenicol-complexes, for example: boric acid/borax or cyclodextrins. Objective: Experimental studies aimed to evaluate the potential advantages of enhancing the solubility and stability of chloramphenicol (API) by molecular encapsulation in b-cyclodextrin (CD), in formulation of ophthalmic solutions buffered with boric acid/borax system. Methods and Results: We prepared four APIb- CD complexes, using two methods (kneading and co-precipitation) and two molar ratio of API/b-cyclodextrin (1:1 and 1:2). The formation of complexes was proved by differential scanning calorimetry (DSC) and the in vitro dissolution tests. Using these compounds, we prepared eight ophthalmic solutions, formulated in two variants of chloramphenicol concentrations (0.4% and 0.5%). Each solution was analyzed, by the official methods, at preparation and periodically during three months of storing in different temperature conditions (4°C, 20°C and 30°C). Conclusions: Inclusion of chloramphenicol in b-cyclodextrin only partially solves the difficulties due to the low solubility of chloramphenicol. The protection of chloramphenicol molecules is not completely ensured when the ophthalmic solutions are buffered with the boric acid/borax system.

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