Azithromycin, a macrolide antibiotic, has a poor stability in solution . The hydrolysis of the a-glycosidic bond in acidic condition yields the major degradation product of azithromycin that is desosaminylazithromycin. One answer to this problem is the application of the freeze-drying process. However, freeze-drying is known as an expensive and time consuming process thus the optimum freeze-drying condition is absolutely important for cost-effective manufacturing. In this thesis, a new, more efficient freeze-drying process for an azithromycin formulation has been successfully developed. Integrated pharmaceutical freeze-dried product development beginning from characterization of the formulation solution, freeze-drying cycle optimization, stability study, and scale-up process was performed. Various thermoanalytical techniques including Differential Scanning Calorimetry, Freeze Drying Microscopy, Thermogravimetric Analysis, and Dynamic Vapor Sorption were used. Scanning Electron Microscopy, X-Ray Powder Diffraction, Raman Microscopy, and HPLC were used as complementary methods to fully characterize the formulation. A significant reduction in freeze-drying time compared to the established process from 98 to 46 hours was achieved without compromising product quality. This time saving could not only increase the production efficiency but also reduce the production cost due to lower power consumption by the freeze-dryer. The stability of the developed formulation was demonstrated for 6 months in 40 °C/75 % RH. The design space of primary drying process of azithromycin formulation was successfully developed based on the heat and mass transfer equation. This model was proven useful to predict the outcome of the product temperature which is the most important parameter that determines the product quality outcome in the freeze-drying process and furthermore makes the scale-up process straightforward. The last part of this thesis discussed the promising possibility of a new drug delivery system based on azithromycin encapsulation in liposomes. Freeze-drying and spray-drying were proven useful in the drying process of this liposomal azithromycin formulation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677851 |
| Date | January 2014 |
| Creators | Wijaya, Harry Martha |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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