Particle Size in Formulations

Particle and droplet size directly influence the bioavailibility and manufacturability of liquid and solid formulations. For example, the development of topical products requires tight control of droplet size and a clear understanding of how the process parameters chosen at each scale influences stability. Tablets break apart into small particles  during dissolution testing  and the rate of disintegration directly influences Active Pharmaceutical Ingredients (API) release rate. Suspensions used to fill meter dose inhalers require tight control over particle size to ensure efficacy for the patient.

Quantifying tablet disintegration profiles in situ and in real time enables scientists to reliably understand the breakage and dispersion mechanisms that govern Active Pharmaceutical Ingredient (API) release rates. This essential process knowledge can support the prediction of in vivo drug release profiles during formulation development, and can help identify the root cause of inconsistencies during release testing.

The resulting mechanistic information complements traditional offline dissolution testing methods, and can support the development and release of bioavailable, stable, and manufacturable dosage forms.

ParticleTrack with FBRM technology continuously monitors changes in particle size and count as capsules an tablets disintegrate and dissolve. The resulting mechanistic information complements traditional offline dissolution testing methods and can support the development and release of bioavailable, stable and manufacturable dosage forms.

ParticleTrack applications include:

• Quality by Design
• Disintegration Kinetics
• Release Mechanism Determination
• Risk Assessment
• FDA Compliance
• Tablet Dissolution for Process Understanding

Mark Menning of the Nucleo Life Sciences presents the role of in-process particle measurement to complement traditional API dissolution studies. The use of in situ particle size and count measurement illustrates efforts to develop process understanding for solid oral dosage form development. This is supplemented by case studies from Amgen, AstraZeneca, and Vertex who use this approach.

Emulsion droplet size and stability are critical parameters to consider during the development of a topical or micro-encapsulated product. Characterizing droplet size effectively allows scientists to solve process bottlenecks and improve product quality. Traditionally, scientists have relied on offline particle size analyzers to perform emulsion and suspension characterization. Offline analysis typically requires sample preparation and sample dilution prior to analysis which, in the case of emulsions, can significantly change the droplet size in an emulsion sample within the time required for preparation and analysis.

The emergence of Process Analytical Technologies (PAT) allows scientists and engineers to track the rate and degree of change in droplet systems as they naturally exists in process without the need for sampling or sample preparation:

• Process Understanding for Emulsions
• Monitoring Multi-Phase systems (Particles and Droplets)
• Scaling-Up Emulsions

Four case studies present how inline Process Analytical Technologies were used to understand, control, and optimize emulsion processing. Topics include creation of  fit-for-purpose droplets, observation of multi-phase systems, and scale-up.

ParticleTrack and ParticleView are probe-based tools that measure changes to particle size, shape, and count in real time. By applying inline analysis to formulation development, scientists can obtain comprehensive process understanding, avoid the errors and time delay associated with offline and ultimately develop formulations with desired attributes in the shortest possible time.   Click Request More Information below to gain technical expertise or to assess the fit of your application with ParticleTrack and ParticleView technology.

A ParticleTrack probe with FBRM technology is immersed into a flowing slurry or droplet system with no dilution necessary. A focused laser scans the surface of the probe window and tracks individual chord lengths - measurements of particle size, shape, and count. This real-time measurement is presented as a distribution and statistics (eg. mean, counts) are trended over time.