Characterization of azithromycin tablets formulated as inclusion complex and stability studies

Purpose: To characterize azithromycin inclusion complex for enhanced solubility and improved release from the dosage form. Methods: Azithromycin was formulated as an inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD) and compressed to produce a tablet by direct compression to enhance the dissolution. The nature of azithromycin molecule in its inclusion complex was investigated using the Infra-Red (IR) and Differential Scanning Calorimetry (DSC) analysis. High-performance liquid chromatography (HPLC) analysis was used to monitor the dissolution rate and stability studies of azithromycin tablets. Two USP protocols of storage were applied at 40 °C with 75 % Relative Humidity (RH), and at 30 °C with 65 % RH. Results: Pure azithromycin scan showed a prominent endothermic fusion peak between 115 and 122 °C, indicating its melting point. Both pure azithromycin and the inclusion complex with HP-β-CD had the same melting point values, according to the thermogram of the DSC. The molecular structure of azithromycin did not change upon inclusion complexation with HP-β-CD, according to IR spectroscopy. According to the HPLC results, retention time and ionic separation efficiency indicate the ion-pair reversed-phase mode of separation of the applied method. Conclusion: The inclusion complex of azithromycin with hydroxypropyl-β-cyclodextrin creates tablets with a high dissolution rate, thereby increasing drug absorption and bioavailability. Azithromycin insertion into the structural cavity of HP-β-CD without a chemical reaction protects the drug molecules from environmental factors and enhances their chemical stability.