In the pharmaceutical industry, it is necessary to perform physical characterization of pharmaceutical excipients to obtain data for assessing asses the performance of final dosage forms such as transdermals, inhaled dosage forms, capsules and tablets.
Particle size is one of these physical testing data specified by manufacturers. The particle size data specified by the manufacturer may differ from the acceptable value for a particular product or process. In addition, other tests such as porosity, density and surface area may not be reported.
In certain cases, these data may be helpful in understanding the behavior of a particular material in final dosage form in terms of bioavailability, dissolution, and disintegration, and in a given process such as compression, blending, and flow.
Significance of Characterization of APIs and Excipients
Gaining insights into APIs and excipients by implementing Quality by Design, design space, control strategies, and risk analysis in accordance with ICH Q8, Q9, and Q10 helps users obtain better understanding of their materials better and the effect of these materials in their formulations.
Microcrystalline cellulose and lactose are widely used excipients in solid oral dosage forms. Unwanted issues may arise owing to variation between lots or suppliers of these materials, especially when they represent the bulk of a formulation.
This experiment demonstrated the degree of consistency of lactose and microcrystalline cellulose by subjecting them to a series of tests. It involved the analysis of three lots of each material to replicate a raw material vendor qualification study.
DFE Pharma provided microcrystalline cellulose (Pharmacel 101), spray-dried lactose (SuperTab 11SD), and anhydrous lactose (SuperTab 21AN). Each material was analyzed for the following physical characteristics:
- Particle size distribution using laser light scattering on the Saturn DigiSizer II
- BET specific surface area analysis with krypton gas on the ASAP 2420 Surface Area Analyzer
- Porosity using mercury intrusion porosimetry on the AutoPore IV 9500
- True or skeletal density by means of helium pycnometry on the AccuPyc 1340
The results for each analysis are summarized in the following table.
||Surface Area (m2/g)
||Particle Size (Volume Distribution)
The use of the results is based on a user's internally developed specification or application as there is no generic right or wrong data set for each product or process. The results may provide information about lot-to-lot similarity or may be helpful in identifying the additional controls required to ensure the suitability of the material for a specific application.
The generated data are more comprehensive when compared to vendor specifications. They can be used to qualify a new raw material supplier, or to implement tighter control for a critical parameter owing to unwanted effects on the performance characteristics of the product of interest. The combination of test results and corresponding product performance data ensures the consistency, robustness, and performance of the product being manufactured.
A key aspect of the overall control strategy for pharmaceutical formulations is raw material monitoring. Understanding the physical characteristics of material is helpful in the development of design spaces or control strategies to ensure product and process quality. Final product performance data can help identify critical quality attributes of raw materials as well as final dosage forms and critical process parameters.
The study results presented in this article demonstrate that a more comprehensive material analysis may help ensure the consistency of the material procured from a particular supplier or in qualifying new material suppliers, and may serve as a predictive factor in assessing product and process performance. Better understanding of raw materials expands the user’s material characterization toolbox for troubleshooting undesirable product or process performance.
This information has been sourced, reviewed and adapted from materials provided by Micromeritics Instrument Corporation.
For more information on this source, please visit Micromeritics Instrument Corporation