Where particle size and performance really matters, Upperton have the expertise
Delivery of treatments by inhalation, directly into the lungs (pulmonary) or to the nasal mucosa (nasal delivery), remains a popular approach to evoke a local or even a systemic response. Therapeutics can be delivered as dry powder, suspension or liquid, from pressurised, pump-actuated or breath-actuated devices.
Spray drying is recognised as the primary technology for engineering next generation dry power formulations with the correct aerodynamic properties needed for successful inhalation, which includes both nasal and pulmonary delivery.
Particle engineering is at the core of formulation development, especially for dry powder inhalers (DPI) or nasal sprays; where the aerosolisation of the powder is crucial to successful delivery of the therapeutic to the target site.
Powder and product characterisation are key for inhaled formulations. Upperton has a range of analytical capabilities to support development activities, including:
- Particle size by laser diffraction
- Spray pattern and plume geometry
- Microscopy including Scanning Electron Microscopy
- Aerodynamic particle size distribution by cascade impactor
- Emitted dose and content uniformity
Drug delivery to the lungs remains a mainstay treatment for respiratory diseases, in recent years there has been increasing interest in delivering systemic treatments by the pulmonary route. This can especially be the case for biotherapeutics, which can take advantage of the large surface area, good blood supply, thin epithelium and avoidance of first-pass metabolism.
To reach the desired region of the respiratory system, a powder particle size of 1 – 5 µm is often required. Furthermore, a narrow particle size distribution is usually needed to increase the effective dose. Spray drying as a manufacturing method to produce spherical powders with excellent particle size, morphology and aerosolisation behaviour is becoming more prevalent. These properties can be tailored through changes in formulation and spray drying parameters, such as feedstock concentration, atomisation pressure and temperature.
One major challenge that occurs during formulation development is collection and subsequently process yield of spray drying powder particles of 1 – 5 μm. In short, small particles can be produced relatively easily using a standard spray dryer but collection becomes increasingly difficult as the particle size drops below 5 μm. Upperton has devised a two-step manufacturing process called PulmoCraft™ to overcome the scale-up issues associated with producing and collecting small particles.
Drug delivery by nasal routes is regularly an approach to achieve systemic delivery, making use of the thin, well vascularised nasal mucosa. Therapies delivered by this route often have very fast onset of treatment as they pass directly into the systemic blood circulation, without first-pass hepatic or intestinal metabolism.
Liquid (solution or suspension) nasal sprays are relatively common and are available for a range of indications, whilst dry powder sprays are gaining traction due to their improved stability. The target particle size for nasal powders is greater than 10 micron to avoid pulmonary delivery. Spray drying can be used to produce a stable, dry powder with narrow particle size distribution. This is especially noticeable for biotherapeutics, which can be difficult to dry into discrete powders for nasal applications.