During the development of liquid parenteral dosage forms, ensuring appropriate product attributes is crucial, as such formulations must comply with stringent requirements regarding quality, safety, and efficacy. One of the key requirements is the absence of visible and subvisible particles, which in most cases necessitates complete dissolution of all formulation components. Consequently, the dissolution of the active pharmaceutical ingredient often represents a significant technological challenge, as inappropriate dissolution conditions may affect formulation preparation time, active pharmaceutical ingredient stability, and ultimately the quality of the final product. The aim of this master's thesis was to investigate the dissolution process of a model active pharmaceutical ingredient during the industrial development of a liquid parenteral pharmaceutical formulation and to evaluate the effects of temperature, pH, and the order of component addition on the dissolution process. The process was investigated using an Optimax reactor equipped with probes for monitoring temperature, pH, conductivity, and turbidity. Dissolution rate was monitored visually and by measuring dissolution time. Visual monitoring was found to be subjective and less reliable, as it was difficult to distinguish between undissolved active pharmaceutical ingredient and impurities/degradation products. Conductivity was identified as the most suitable objective parameter for determining the dissolution time, whereas turbidity was not appropriate due to the insufficient sensitivity of the probe. Determination of dissolution time based on pH changes was only suitable when the processes were conducted at the same constant temperature. The dissolution process did not show a significant endothermic or exothermic nature. The results showed that the active pharmaceutical ingredient dissolved most rapidly at 10 °C and 25 °C. pH appeared to have a more pronounced effect on dissolution than temperature, with the fastest dissolution achieved at pH 11. The combination of pH 11 and a temperature of 10 °C proved to be the most favorable, as it resulted in the shortest dissolution time while maintaining active pharmaceutical ingredient stability throughout the process. The analyses showed that the degradation product was not formed during the dissolution process but was most likely already present in the active pharmaceutical ingredient powder. Furthermore, the dissolution rate of the degradation product appeared to be temperature-dependent, suggesting retrograde solubility behavior. The order of formulation component addition was also found to significantly affect both the success and duration of solution preparation. The sequences ZU-PS1-PS2 and PS1-ZU-PS2 proved to be the most suitable.
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