Advancements in Nasal Spray Formulation: The Role of Morphologically-Directed Raman Spectroscopy and Laser Diffraction

Breaking down the science: Optimizing nasal sprays with advanced particle analysis

The nasal spray market is on the rise, driven by innovations in drug delivery and increasing global demand. Yet, delivering drugs effectively through nasal sprays presents unique challenges.

Without proper particle analysis, nasal sprays risk being ineffective or unsafe. For example, particles that are too small may bypass the nasal cavity and deposit in the lungs, while instability in biologics can lead to aggregation, reducing efficacy and increasing risks.

This article explores the latest market, technological, and regulatory insights shared in a webinar hosted by Malvern Panalytical’s Marketing Segment Manager, Rob Taylor. The session focused on three particle size analysis techniques that are pivotal for ensuring the efficacy, safety and stability of nasal spray formulations, including complex biologics.

Key takeaways

• Market trends: The nasal spray market growth is fueled by urbanization, the rise in allergens, and the demand for systemically acting drugs.
• Technology advancements: MDRS is now recognized by the FDA as a technique to characterize complex intranasal formulations and this compliments droplet size distribution when understanding drug delivery.
• Biologics stability: Techniques like DLS and laser diffraction ensure the stability of biologics, which may be prone to aggregation due to the actuation process in nasal sprays.

"There's a renewed interest in nasal sprays, driven by rising demand, increased research on the nose-to-brain route, and new drug delivery modalities.” – Rob Taylor.

Market insights

The nasal spray market, valued between $25 billion and $35 billion, is poised for robust growth over the next decade, with high single-digit compound annual growth rates expected. This growth is driven by multiple factors, including rising allergies due to urbanization, which leads to higher allergen exposure that drives demand for locally acting nasal sprays that provide targeted relief.

Regulatory innovations are also boosting the growth of the market through the adoption of innovative approaches such as in-vitro bioequivalence tests. These help manufacturers bring generic nasal products to market faster and at lower costs. There are also increasing applications for nasal sprays beyond locally acting drugs, such as brain and central nervous system-acting drugs. Drug modalities delivered via nasal sprays include traditional small molecules, peptides, hormones, and vaccines, demonstrating the diversity and potential of this growing sector.

Technology overview

Advanced particle analysis techniques are revolutionizing nasal spray development by providing precise insights into particle behavior, droplet distribution, and formulation stability.

Morphologically directed Raman spectroscopy (MDRS)

MDRS enables detailed particle characterization by combining light microscopy with Raman spectroscopy. It identifies drug particles and other components in complex formulations to give component specific particle morphology. The FDA now acknowledges MDRS as part of the toolset for in-vitro bioequivalence, particularly for generic nasal sprays.

“For locally-acting drugs prepared as suspensions, particle size is crucial. According to Noyes-Whitney kinetics, dissolution rates correlate with particle size, which controls drug release and, ultimately, the biological effect. Particle size also influences the stability of biologics, and can serve as an indicator of stability.” – Rob Taylor

Laser diffraction

Measuring droplet size distribution during spray actuation requires a fast and precise analysis as the spray event occurs in fractions of a second. Laser diffraction does this and systems can be configured to capture data on different phases of spray formation. Knowing the droplet sizes during the fully developed phase will help predict where they will deposit in the nasal cavity.

Dynamic light scattering (DLS)

DLS is particularly valuable for biologics. It measures nano-scale particle size changes to monitor aggregation and stability under stress. This is relevant for nasal sprays as device actuation and aerosolization create shear stresses that can cause proteins to unfold and aggregate. DLS is highly sensitive to these nano-scale changes and is routinely used in stability assessment for biologics. It is now becoming a widespread technique to test the effects of device actuation.

Regulatory and practical implications

The use of advanced technologies like MDRS, laser diffraction, and DLS provides significant advantages in meeting regulatory requirements and addressing practical challenges. By measuring particle size directly with these techniques and conducting dissolution tests, manufacturers can make use of now-approved bioequivalence instead of more time-consuming in-vivo studies for certain formulations.

For both generic and innovative nasal sprays, controlling particle size and droplet distribution is crucial for ensuring deposition in the desired area of the nasal cavity. Adjustments to formulation viscosity, as shown in PVP studies during the webinar, highlight how small changes can significantly impact particle size and plume geometry. MDRS, laser diffraction, and DLS enable tight control of such parameters.

DLS also aids in overcoming one of the most pressing challenges in biologics: aggregation under stress. By detecting particle size changes at the nanoscale, DLS provides early indicators of stability issues, allowing for timely formulation adjustments.

MDRS, DLS, and laser diffraction thus enable manufacturers to develop high-quality nasal sprays that meet stringent regulatory standards while ensuring product efficacy and safety.

Watch the webinar to learn more. If you have any questions or want to book a demo of our MDRS, DLS, or laser diffraction instruments, contact our experts!