Optimization of lyophilization cycle for the formulation and stability assessment of Doxycycline Hyclate

Abstract

Background and Aim:Doxycycline hyclate, prone to instability in solution, is unsuitable for liquid dosage forms. Lyophilization, a low-temperature drying process, addresses this limitation by converting the drug into a stable solid. This study aimed to optimize the lyophilization cycle for doxycycline hyclate, enhancing its stability, handling, and transport in injectable form Methods:
Pre-formulation studies included solubility analysis, pH determination, water content measurement, FTIR, DSC, photostability, and compatibility studies. Twelve lyophilization cycles were designed, optimizing four formulations by varying temperature, pressure, and cycle duration. Formulations were assessed for cake appearance, solution clarity, pH, reconstitution time, and assay. The optimized formulation underwent additional evaluations for diluent and filter compatibility, in vitro antibacterial activity (disk diffusion), and stability under accelerated and photostabilityconditions.Results:Formulation F3 from Trial 3 exhibited superior performance, with a uniform, smooth cake appearance, clear reconstitution, stable pH, rapid reconstitution time, low water content (0.98%), and minimal organic impurities. Diluent and filter compatibility tests revealed no adverse interactions. The formulation remained stable under light and accelerated conditions, showing dose-dependent antibacterial activity comparable to the innovator’s product.Conclusion:The optimized lyophilization cycle significantly enhanced doxycycline hyclate's stability, handling, and transport. The injectable formulation demonstrated excellent stability, reliable antibacterial activity, and clinical suitability, offering a safer, more convenient alternative to liquid formulations.