OINDP testing

Assay of actives and impurities

The drug content and impurities of the formulation are crucial stability indicating parameters. At Kenox we emphasize robust and reliable analytics since the results guide crucial decisions throughout the development. We offer deep expertise in efficient method development. Kenox is experienced in various HPLC methods including reversed phase, HILIC, SCX, SEC, ion pair, ligand exchange, pre-column derivatization etc.

In addition to method development, Kenox offers verification of compendial methods, validation of internal methods, forced degradation studies as well as impurity profiling.

Delivered dose uniformity

The delivered dose uniformity (DDU) of DPIs, SMIs or MDIs is typically performed using a constant testing flow rate with a defined air volume. In general, the device is actuated into a DUSA tube which is subsequently worked up and the delivered dose is determined by HPLC analysis.

The delivered dose testing of nebulizers requires tidal breathing provided by a breathing simulator. Kenox offers a variety of breathing profiles for regulatory requirements or to mimic (impaired) patient profiles.

Kenox conducts delivered dose testing for all OINDPs according to regulatory requirements (Ph.Eur. and USP).

Droplet size distribution

The droplet size distribution (DSD) is determined by laser diffraction. Here, the aerosol is entrained into a laser beam and the resulting diffraction pattern is recorded by a detector. DSD is derived from this diffraction pattern.

DSD testing can be performed either in an open bench configuration or using a dedicated inhalation module which offers the use of different induction ports and an air flow rate. Moreover, this setup can be coupled with cascade impaction for simultaneous results or cross-validation purposes.

Aerodynamic particle size distribution

Aerodynamic particle size distribution (APSD), a gold standard in inhalation research, is determined by cascade impaction. The aerosol is guided by an airflow through a series of impaction stages representing different size classes. The most commonly used impactor is the Next Generation Impactor (NGI). Kenox also offers APSD testing using the Andersen Cascade Impactor (ACI) or the Multistage Liquid Impinger (MSLI).

APSD testing is routinely applied for orally inhaled Nebulizers, DPIs, SMIs and MDIs. For nasal products, it is used to quantify a potential inhalable fraction (Drug in small particles), an important safety related parameter.

It is important to understand the nature of the aerosol (wet droplets vs solid particles) for accurate measurements. Kenox is an expert in developing robust APSD methodologies considering droplet evaporation, inter-stage bounce, recoveries etc.

APSD testing is performed according to Ph.Eur. and USP. 

Spray pattern and Plume geometry

Spray pattern (SP) and plume geometry (PG) are also determined by laser diffraction. Aerosol is entrained into a laser sheet rather than a laser beam. The resulting interaction is then recorded by a camera positioned at a defined distance and angle. Spray pattern describes the size and shape of the area covered by the aerosol at defined distances from the device, and this is typically presented in terms of area and ovality. The plume geometry is described by the plume width and angle at a defined distance.

Priming and Re-priming

The priming and re-priming testing is a typical test for multi dose products which rely on certain metering principles. It determines the number of actuations necessary until a consistent aerosol meeting requirements is emitted. It is also a typical in-use stability test which aims to mimic the patient’s use.