QC Spotlight: Particle Size Analysis

The Malvern Mastersizer 2000

In the pharmaceutical industry, particle size plays a critical role in the formulation of a drug product especially for solid oral dosage forms. It can impact the product stability, dissolution profile, efficacy, and ultimately the bioavailability. Typically the lower the dosage strength the smaller the particle size requirements are that are needed to develop a stable formulation. PCI works closely with all of it’s finished dosage customers to develop particle size specifications that can not only be met by our manufacturing process but can be measured in a reproducible fashion. In 2006 PCI acquired a new Malvern Mastersizer 2000 which has been fully validated and gets continuous use. Although it certainly gets a lot of usage for approving final products it is also a critical instrument during process development. 

The Mastersizer 2000 is a highly efficient and advanced particle size analyzer in our QC Lab. The unit comes equipped with two sampling accessories one for  wet and one for dry measurement. The accessory employed (wet vs. dry) depends exclusively on the nature of the material to be analyzed.  Many materials need to be measured in a wet dispersion apparatus. Usually this is needed when the  materials themselves will be used in a wet manufacturing process (wet blending), certain sticky materials, or materials that have a tendency to agglomerate when dry. For materials that are used in a dry manufacturing process, such as direct compaction, dry blending, powder coatings, and micronization, dry measurement is usually preferable. By having both accessories PCI has the capability to measure a great number of different materials that are used as active ingredients.

Key Hightlights of the Mastersizer 2000

Broad Measurement Capability: Measures materials from 0.02µm to 2000µm
Automated System: The system is completely controlled by the computer’s software during the measurement proces
Accuracy and Reproducibility:
Accuracy: less than 10% on the Dv50 on most APIs
Reproducibility: PCI methods and SOPs eliminate user variability
Regulatory Compliance: Full validation documentation available and complies with 21 CFR Part 11

Hightlights of  the Dry Accessory (Scirocco 2000)
The sample feed rate can be controlled by the amplitude of vibrations on the sample tray and also by the gap between the feed gates.

The vibrating ball bearings on the sieve tray can smooth the flow of the fed sample and break up any loose agglomerates within the sample.

Hightlights of the Wet Accessory (Hydro 2000S)
The small volume tank is ideal for both a small amount of sample and dispersant.
The variable pump/stirrer allows a wide range of particle sizes and densities to be suspended and circulated.
The variable power ultrasonic system enables particle agglomerates to be dispersed quickly and easily

The Malvern Mastersizer 2000 at PCI
Since the Malvern Mastersizer is a sophisticated and sensitive instrument powered by a powerful laser all annual preventive maintenance is strictly performed by Malvern certified technicians. PCI has written and utilizes numerous SOP for the operation of the instrument and it’s individual accessories. Each API requires method development and validation thus resulting in additional documentation specific to each API. All analysts continuously undergo rigorous training to insure constant reproducibility with each analytical run.

PCI uses the Malvern Mastersizer to determine not only the  API’s  particle size but also the particle size distribution within a sample. What is typically reported is the D(.01), D(0.5) and D(0.9). Which is the mean  particles size which is less than 10%, 50% and 90% of the particles respectively. During process development the goal is to develop both crystallization and milling conditions that not only result in the right particle size but also the right distribution. Analysis can be done in real time by taking samples, analyze them, and then adjust process conditions (milling or crystallization) and then re-analyze to see if the new conditions will meet specification. The ultimate goal is to eliminate the possibility of clumps in the product and make sure the product size is uniform to meet the customer’s specification.

The Malvern generates an easy to read distribution report and automatically reports all it’s results. The example below is for a Disulfiram (USP) sample that was produced in our Newburyport plant.

Having particle size issues with your API? Call our Business Development Team as PCI has both the analytical and plant equipment to process your material to your specifications.

Contact Melissa Huang at (508) 533-5012 for additonal information.