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.

Popular Abstract

The focus of my thesis work was Rhinocort®, which is a nasal spray for allergy treatment, which is a highly abundant disease and is often undertreated, thus can lead to missed school, -or workdays. Rhinocort® must be tested before it is marketed to ensure good quality and patient safety; one of these tests includes measuring its viscosity. The viscosity value must be within a certain acceptance limit for the product to be marketable, which is 5.0 - 8.5 mPas.
Viscosity can be best understood as the resistance to flow; when we compare the flow properties of honey and water, we can conclude that honey is more viscous as it is much harder to pour out of the jar. Rhinocort® has a so-called thixotropic behaviour, which was assessed throughout some experiments. A thixotropic material becomes less viscous as the force applied to it increases, and this also depends on how long it is exposed to this force.
According to the current test method, 10 days must pass by after production before viscosity tests can be carried out, which leads to high storage costs and hinders production. Therefore, my thesis aimed to shorten this period to save resources and money. Together seven different types of experiments were executed.
For examining the temperature dependence and shaking time dependence, some scientific articles served as the basis, as these suggested an increase in viscosity by lowering the temperature and shortening the time of disturbance (shaking). The product’s flow behaviour and its resistance toward mechanical interferences were assessed by various tests, as well as the re-occurring problem, called sedimentation. Furthermore, placebos (the product without the active pharmaceutical ingredient) were mixed to experiment with achieving a higher initial viscosity value.

• author: Domián, Lili Zsófia
• supervisor: Marie Wahlgren
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLGM05 20231
• year: 2023
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: Rhinocort, viscosity, rheology, thixotropy, pharmaceutical technology
• language: English
• id: 9116876
• date added to LUP: 2023-05-26 09:13:04
• date last changed: 2023-05-26 09:13:04