QC Spotlight: Particle Size Analysis
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, bioavailability. Typically the lower the dosage strength, the smaller the particle size requirements that are needed to develop a stable formulation. PCI Synthesis works closely with all of its finished dosage customers to develop particle size specifications that can be met both by our manufacturing process and also can be measured in a reproducible fashion.
Our QC lab relies on a Malvern Mastersizer 2000, a highly efficient and advanced particle size analyzer. 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 Synthesis has the capability to measure a great number of different materials that are used as active ingredients.
Key Highlights 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 process.
- 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.
Highlights 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.
Highlights 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 Synthesis
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 Synthesis has written and utilizes numerous standard operating procedures (SOP) for the operation of the instrument and its 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 Synthesis 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 less than 10%, 50% and 90% of the particles, respectively. During process development, the goal is to develop both crystallization and milling conditions that results both in the right particle size and also the right distribution. Analysis can be done in real time by taking samples, analyzing them, and then adjusting process conditions (crystallization, milling, micronization) and then re-analyzing to see if the new conditions 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 Mastersizer generates an easy to read distribution report and automatically reports all its 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 Synthesis has both the analytical and plant equipment to process your material to your specifications.