engleski

Design of experiments in formulation of spray dried co-excipient

Various technologies have been applied for formulation of excipients and co-excipients. Despite some process disadvantages, spray-drying technology emerges as a favorable one. Numerous possibilities of this process have not been yet fully explored, at least not in the area of preparation of pharmaceuticals. Still, the powders prepared with this process technology have better properties compared to products prepared by other concurrent technologies. One particular advantage emerges as a crucial one, especially in formulation of pharmaceutical ingredients. That is, spray-drying produces powders of high homogeneity. In this study, co-current spray-drying technology was utilized for the formulation of pharmaceutical co-excipient with enhanced target property. Two component mixture of α-lactose monohydrate and polyvinylpyrrolidone (PVP) was used as the co-excipient. The effect of process variables (inlet drying air temperature and feed rate) on the target property of the excipient (particle size distribution) was investigated. Process was analyzed using the full factorial design of experiments with application of Design-Expert® 6 software. Two factors were changed at two levels, and four experiments were carried out at different process conditions. Also, they were all repeated in order to test reproducibility of the process. Parameter of volume specific surface area allows integral indication of particle size distribution and therefore was used as a relevant process response in design of experiments. Obtained results indicate alterations in specific surface area in the case of simultaneous change of the process variables. Increasing only one variable results with excipients of poor quality and substantial sticky affinity. ANOVA statistical analysis results with model correlating specific surface area of the excipient and process variables. Derived statistical parameters indicate non-significance of the resulting model. Influence of both process variables has been also found as a quite non-significant. However statistical results provide a good insight into the complexity of the spray-drying process. Model improvement can be achieved with integration of additional process variables in statistical analysis. Multiscale approach must be used for getting comprehensive perspective of the process. This will allow quantification of the complex synergy between two underlying phenomena, feed atomization and drying kinetics.

spray drying; excipient; particle size distribution; design of experiments

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