Using Cold-Stage MDRS to Study Temperature-Driven Particle Changes in Nasal Spray APIs
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Cold-Stage MDRS Investigation of Beclomethasone Dipropionate:
In Situ Monitoring Morphological and Chemical Stability of Nasal Spray API Across Different Temperatures​
Authors:
Dr Jabbar Gardy
Dr Jabbar Gardy is a Technical Leader in Physical Characterisation with a PhD in Chemical Engineering.
Caroline Aiken
Caroline Aiken has been successfully growing and leading the Physical Characterisation team at Bradford for the past 6 years.
Caroline German PhD FRSC
Caroline German is Operations Director at Cormica Bradford with over 25 years’ experience in analytical chemistry, physical characterisation, and GMP.
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What and why we are doing: INTRODUCTION
- Nasal drug delivery is increasingly important due to rapid systemic absorption and avoidance of first-pass metabolism.
- Beconase® nasal spray, as a case study of OINDPs, contains beclomethasone dipropionate (BDP) active pharmaceutical ingredient (API) in an aqueous suspension delivered via a metered-dose actuator.
- Suspension stability requires tight control of particle characteristics during manufacturing, storage, and use.
- Wide global ambient temperature fluctuations during transport/storage has the potential to induce particle size / shape changes in the API of such formulations, potentially altering crystal habit or morphology, and impacting overall product performance if temperature is not adequately controlled.
- Morphologically-directed Raman spectroscopy (MDRS) combines automated image analysis + Raman ID = distinguishes API vs excipients.
- Cold-stage MDRS extends this by allowing for the mimicking real-world storage and use conditions during analysis.
Objectives:
- Develop and test a first bespoke cold-stage integrated with MDRS.
- Examine temperature-driven morphological changes of BDP API.
- Assess excipient stability under identical conditions.
How we are doing it: METHODS
- Commercial Beconase® (BDP API 50 µg/spray, Boots Pharmacy, UK) was used as a model nasal spray for analysis.
- Novel custom built cold-stage was coupled with MDRS and used for the inline analysis of particle size, shape and chemical identification of the BDP API and excipients within the Beconase® formulation at different temperatures.
- Sample preparation method was developed and instrumental configuration parameters optimised for this application.
- Investigate the impact of real-world storage and transport conditions on the API and excipients particles within the formulations.
What we have found: RESULTS
Manual Microscopic Images of Captured Particles at Various Temperatures:
Automated Microscopic Images of Captured Particles at Various Temperatures:
Particle Size Distributions of BDP API and Cellulose Excipient Particles:
Overlaid Size Distributions of Different Particle Classes within the Beconase at Different Temperatures. Colour-coded Lines: Red Line: 25 °C; Green Line: 37 °C; and Blue Line: 50 °C
Chemical Identifications of Different Particle Classes within the Beconase Nasal Spray:
What it means: CONCLUSIONS
- A novel custom-designed Cold-Stage coupled with MDRS and used for the first time to monitor in situ of temperature-dependent morphological and chemical stability of BDP API and excipient in Beconase® nasal spray formulation.
- It was found that BDP API particles were temperature sensitive, with pronounced morphological changes at elevated temperatures (37 °C), whilst cellulose excipients showed greater structural resilience under the same conditions.
- Observed marked volume expansion of cellulose particles at higher temperatures (50 °C), further supporting their differential response compared with BDP API particles.
- Next stage will focus on low-temperature and inverted storage orientation conditions.
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