Nasal spray development and characterisation

The administration of drugs via the nasal route has been a preferred one for many years, and is widely popular for local, systemic, as well as delivery to the central nervous systems. Intra-nasal administration is currently being explored to a great extent with many vaccines, peptides as well as hormonal formulations in the pipeline at different stages of clinical trials.

Types of nasal sprays

Depending on the intended use of the finished product, physicochemical properties of the active and formulation characteristics, nasal sprays can be multi-dose, unit dose and bi-dose.

Multi-dose nasal sprays

These sprays have the lion’s share in the market. The drug formulation (solution or suspension) is filled in a bottle (glass or HDPE) that is closed with a nasal spray pump attached with a dip tube. An actuator is also present. The pumps are displacement type and can be crimp-on, screw-on and snap-on.

Historically, metered-dose nasal sprays contain preservatives in their formulations. However, preservative-free pumps are slowly becoming a preferred choice to develop novel products.

Another configuration that has been marketed for many years (popular in the OTC segment) is the squeeze bottle.

Unit dose and bi-dose nasal sprays

Unit and bi-dose nasal sprays are designed to deliver precisely one or two doses of the medication upon actuations. They are ready-to-use products and are preferred for emergency and acute therapies. In both types of products, the formulation is filled in special micro-vials that are stoppered with rubber plunger (chlorobutyl or bromobutyl). This stoppered vial is integrated with the unit dose or bi-dose device (vial holder and actuator).

Nasal spray development

Nasal sprays are combination products where the formulation and device play a pivotal role in performance. Product delivery from the device governs the performance characteristics of the finished product. Therefore, it is essential to have a robust manufacturing process coupled with a compatible device.

 Nasal spray characterisation

In addition to general physicochemical tests such as pH, viscosity, osmolality, assay of active, preservative content, impurities and microbial limit tests, the performance characterisation of nasal sprays are of paramount significance. These tests give us insights about pump performance.

• Spray pattern and plume geometry: Characterisation of spray pattern and plume geometry are important for evaluating pump performance. Various factors can affect the spray pattern and plume geometry, including the size and shape of the nozzle, the design of the pump, the size of the metering chamber and the characteristics of the formulation.
• Droplet size distribution: This test can be performed using a laser diffraction method. Droplet size distribution can be controlled in terms of ranges for the D₁₀, D₅₀, D₉₀, span [(D₉₀-D₁₀)/D₅₀], and percentage of droplets less than 10 mm.
• Pump delivery: This test is used to assess pump-to-pump reproducibility in terms of drug product performance and to evaluate delivery from the pump.
• Single Actuation Content (SAC): SAC should be compared at the beginning, middle and end stages of the drug product lifecycle according to USP monograph or using apparatus B or another validated method. The drug product should be tested at a specified range of flow rates. The population bioequivalence (PBE) approach should be used for statistical evaluation, which assumes a log normal distribution.
• Drug in small particles/droplets: Sizing of droplets or particles by multi-stage Cascade Impactor (CI) measures aerodynamic diameter based on inertial impaction; an important factor in deposition of the drug in the nasal passages. Analytical data should be based on a validated chemical assay.

The nasal route offers numerous advantages for local, systemic as well as nose-to-brain drug delivery. Considering the current regulatory landscape and complex manufacturing technologies, the successful development of a nasal spray product would require expertise of a robust manufacturing process and optimal device performance.

About Rubicon Research’s capabilities

We have a 15,000 square feet development and testing facility specializing in pulmonary and nasal drug delivery systems in Concord, Canada. It is a USFDA-inspected and Health Canada approved laboratory and facility. Our manufacturing facility includes fully automated filling lines for unit dose and multi-dose nasal sprays.

 From development to commercial

Our capabilities cover both development and commercial scale manufacture of unit dose, bi-dose, and multi-dose nasal sprays in environmentally controlled production facilities. With an excellent history of regulatory approvals, we can onboard projects at any stage of their lifecycle—from initial concept, through formulation and analytical method development/optimization, clinical manufacturing, and commercial manufacturing.

To know more visit www.rubicon.co.in or contact [email protected]