Design of experiments in the development of nasal spray

Various statistical approaches are being used during the development of pharmaceutics. One of most powerful tools is Design of Experiments, which can be used to systematically study impact of factors on critical quality attributes (CQA).

Nasal sprays belong to a class of complex pharmaceutcial dosage forms, composed out of two major components: formulation (suspension) and delivery device (spray). One of key CQA for nasal sprays is geometry of a plume (spray pattern, cross-sectional profile), which is formed when nasal spray is actuated. Geometry of a plume defines area of dose deposition within nasal cavity (narrower spray pattern, longer projection, and vice versa).

With systematic analysis of factors and definition of significant ones, linear regression model can be build for, called also »Resposne surface model« . By applying factors of variability and uncertainty to the model using Monte Carlo simulations, one can perform Risk analysis and define optimal leveles of factors to achieve desired spray pattern.

Presentation will include key steps: understanding of nasal sprays and potential factors, design of experiment, statistical evaluation of factors and optimization of linear regression model, risk analysis (Monte Carlo), practical application of created model, validation of model.