Sekundarni povzetek: |
The primary drying phase is the most cost-effective and time-consuming phase of the lyophilization process and can represent up to 50 % of the entire lyophilization cycle. For this reason, the main purpose of this work was the development of an aggressive lyophilization cycle, whereby the appropriate selection of aggressive process parameters would shorten the primary drying phase, but nevertheless, the final product of acceptable quality would be obtained. In order to evaluate the effect of the formulation composition on the product characteristics and the sublimation rate, in all the freeze-drying cycles, 2 formulations were lyophilized, namely an amorphous formulation with sucrose and a partially crystalline formulation with sucrose and glycine. After each cycle, the lyophilization process was evaluated using process graphs, while the selected properties of the lyophilizates were determined by appropriate analytical methods. The occurrence of collapse was evaluated by a visual examination, with all the lyophilizates showing an acceptable appearance and without significant visible changes in the structure of the cake. After reconstituting lyophilizates with water, all of them dissolved rapidly, and the resulting solution was clear and free of visible particles. Based on the results of DLS and SEC measurements performed in the solution prior to lyophilization and after the reconstitution of lyophilizates, the occurrence of protein aggregation during the lyophilization process and during stability testing could be excluded. The residual water content, as determined by the Karl-Fischer titration method, was in all analyzed samples less than 2 % (m/m), which is in terms of stability a favorable result for most lyophilizates. The morphological properties of lyophilizates were evaluated by SEM, where traces of breaking and melting of the cake were observed, indicating the occurrence of microscopic collapse in products of aggressive cycles. While evaluating the lyophilization process, we focused primarily on the primary drying phase, which was reduced by 40-45 % by using the aggressive drying conditions. Thus, the duration of the entire lyophilization process was reduced by approximately 35 % compared to the basic conservative liophilization cycle. In this way, we greatly increased the time- and cost-effectiveness of the lyophiliazation process, without significantly affecting the quality of the final product. |