Storage period optimization of a viscous nasal spray suspension

Abstract: The number of people suffering from the unpleasant symptoms of allergic rhinitis is increasing due to environmental and other factors. This not only makes life difficult for the individual but also places a heavy burden on society, which is why treatment is needed. Rhinocort® is a nasal spray suspension manufactured by McNeil AB to reduce the severity of symptoms, and like all medicines, must undergo quality testing. One of these tests is viscosity measurement, which currently is only carried out 6-10 days after production. Therefore, the aim of my thesis was to increase the understanding of the rheology of Rhinocort® and to suggest strategies for shortening the waiting period prior to the viscosity assessment. A rotational rheometer was used to determine the viscosity of the product. Various methods were set up to evaluate the temperature dependence, recovery, and robustness of the product. In addition, tests were carried out to investigate the influence of different shaking times prior to the measurements. As sedimentation is a recurring phenomenon in the product, this was assessed by amplitude, frequency sweep, and particle size distribution tests. Placebos were also formulated to achieve a higher initial viscosity. All experiments were successful, as higher viscosity values were achieved by increasing the storage temperature. It was also found that the regeneration of the product after disturbance only takes less than one hour and the suspension itself is incredibly stable. Increasing the shaking time has been shown to have a negative effect on viscosity as it leads to structural destruction. Sedimentation has been shown to start as early as day 0, but this has nothing to do with the overall quality of the product as shown by particle size distribution tests. Additionally, a placebo formulation was done to see if a higher initial viscosity could be achieved by altering the sodium-carboxymethyl-cellulose (NaCMC) content, the excipient responsible for increasing viscosity. The objectives set with the company were all fulfilled, as the viscosity change was studied in 10 batches between day 0 – day 10 and the above-mentioned tests were performed. I believe that the viscosity testing could be done on day 0 as this value is within specifications. It is important to mention that the goal document submitted to the university portal was based on a preliminary literature search, as it became clear on-site that some experiments are not possible. Also, as always, there is room for further experiments, and my suggestion would be to examine the viscosity of more batches on day 0 to gather further evidence for my proposal, as I believe that the viscosity test could be done already on this day.