Formulation and in Vivo Evaluation of Dry Powders for Reconstitution of ‎Solubility-Enhanced Derivative of Azithromycin Dihydrate

Sravya Maddukuri , Radha GV

Abstract

The aim of this research was to formulate antibiotic dry syrup, which would indicate increased physical and chemical stability during its intended shelf life. Antibiotic azithromycin dihydrate, utilized to cure bacterial infections, is not soluble and stable in water. Hence, pediatric oral powders for suspensions are available which are merely stable only for 5 days after reconstitution. The solubility of azithromycin dihydrate was first improved by solid dispersions, inclusion complexation, and nanosuspensions. Then, the same was used in dry syrups. By this, solubility and stability could be improved, and taste masking could be achieved. Solubility enhancement was performed by the use of poloxamer 188, poloxamer 407, and polyethylene glycol 20,000 as carriers in two different concentrations and two techniques (solvent evaporation and freeze-drying). Similarly, inclusion complexation using β-cyclodextrin, epichlorohydrin-β-cyclodextrin, and sulfobutyl ether cyclodextrin was attempted using solvent evaporation and freeze-drying. Nanosuspensions were also prepared using poloxamers and PVP, by nanoprecipitation with cryoprotectants. All the solid dispersions, inclusion complexes, and nanosuspensions were characterized utilizing in vitro dissolution profiles, kinetic modeling, X-ray diffractometry, and SEM images. In vitro dissolution profile data revealed a notable increase in drug release with inclusion complexes (using sulfobutyl ether cyclodextrin and prepared by freeze-drying) and nanosuspensions (using poloxamer 188 and prepared by nanoprecipitation with cryoprotectants). X-ray diffractograms showed a reduction in crystallinity. Kinetic modeling revealed a zero-order release mechanism. Hence, two inclusion complexes and two nanosuspensions were used to formulate dry syrups using Viscarin ph 209 and Gelcarin ph 812 as suspending agents. Powdered dry syrups were evaluated before reconstitution for their flow properties, and results showed excellent flow properties. Post-reconstitution evaluation results also suggested a stable and flocculated oral suspension with sedimentation volume closer to 1 over the tested period‎‎.



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