Expanding the Material Characterization Toolbox for Excipient and Active Pharmaceutical Ingredient (API) Vendor Qualification

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.

Experimental Procedure

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

Experimental Results

The results for each analysis are summarized in the following table.

Materials Lot Density (g/cc) Porosity (%) Surface Area (m2/g)
SuperTab 21AN 10678881 1.5821 8.5783 0.3490
10640579 1.5810 8.5917 0.3442
10680069 1.5798 11.1114 0.3452
Mean 1.5810 9.4271 0.3461
% RSD 0.07 15.5 0.73
SuperTab 11SD 10614997 1.5389 3.4083 0.2172
10643209 1.5391 2.8102 0.2207
10641963 1.5384 3.0303 0.1892
Mean 1.5388 3.0829 0.2090
% RSD 0.02 9.8 8.26
Pharmacel 101 00100016 1.5495 18.6942 1.3805
00100014 1.5545 16.3986 1.3345
00100018 1.5527 16.9754 1.3792
Mean 1.5522 17.3561 1.3647
% RSD 0.16 6.9 1.92

Material Lot Particle Size (Volume Distribution)
Mean D90 D50 D10
SuperTab 21AN 10678881 132.874 299.980 118.163 1.286
10640579 123.902 278.460 111.046 1.184
10680069 137.314 298.012 128.024 1.399
Mean 131.363 292.151 119.078 1.290
% RSD 5.2 4.1 7.2 8.3
SuperTab 11SD 10614997 59.168 117.334 53.639 4.146
10643209 67.634 124.826 65.090 11.091
10641963 69.883 136.195 64.786 7.324
Mean 65.562 126.118 61.172 7.520
% RSD 8.6 7.5 10.7 46.2
Pharmacel 101 00100016 51.810 98.606 49.353 7.824
00100014 55.109 103.303 53.231 9.020
00100018 57.587 105.306 56.397 11.028
Mean 54.835 102.405 52.994 9.291
% RSD 5.3 3.4 6.7 17.4

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.

Conclusion

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

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