The application of multiple linear regression to the measurement of the median particle size of drugs and pharmaceutical excipients by near-infrared spectroscopy

Abstract

A number of powdered drugs and pharmaceutical excipients were used to demonstrate the ability of near-infrared spectroscopy to measure median particle size (d₅₀). Sieved fractions and bulk samples of aspirin, anhydrous caffeine, paracetamol, lactose monohydrate and microcrystalline cellulose were particle sized by forward angle laser light scattering (FALLS) and scanned by fibre-optic probe FT-NIR spectroscopy. Two-wavenumber multiple linear regression (MLR) calibrations were produced using: NIR reflectance; absorbance and Kubelka-Munk function data with each of median particle size, reciprocal median particle size and the logarithm of median particle size. Best calibrations were obtained using reflectance data versus the logarithm of median particle size (NIR predicted lnd₅₀versus ln(FALLS d₅₀) for microcrystalline cellulose and lactose monohydrate sieve fraction calibrations: r = 0.99 in each case). Working calibrations for lactose monohydrate (median particle size range: 19.2–183 µm) and microcrystalline cellulose (median particle size range: 24–406 µm) were set-up using combinations of machine sieve-fractions and bulk samples. This approach was found to produce more robust calibrations than just the use of sieved fractions. The method has been compared with single wavenumber quadratic least squares regression using reflectance and mean-corrected reflectance data with median particle size. Correlation between NIR predicted and FALLS values was significantly better using the MLR method.

References

1. M. E. Aulton, Pharmaceutics: The Science of Dosage Form Design, Churchill Livingstone, Edinburgh, 1988.
2. H. G. Barth, S. Sun and R. M. Nickol, Anal. Chem., 1987, 59, 142.
3. C. Washington, Particle Size Analysis in Pharmaceutics and Other Industries, Ellis Horwood, New York, 1992.
4. British Pharmacopoeia 1993, HM Stationery Office, London, 1993, vol. 2, Appendix XVII, A & B.
5. A. Simmons, International LABMATE, 1993, 17, 23.
6. P. A. Hailey, P. Doherty, P. Tapsell, T. Oliver and P. K. Aldridge, J. Pharm. Biomed. Anal., 1996, 14, 551.
7. P. Frake, C. N. Luscombe, D. R. Rudd, J. Waterhouse and U. A. Jayasooriya, Anal. Commun., 1998, 35, 133.
8. P. Dubois, J. Martinez and P. Levillain, Analyst, 1987, 112, 1675.
9. W. Plugge and C. van der Vlies, J. Pharm. Biomed. Anal., 1993, 11, 435.
10. C. van der Vlies, W. Plugge and K. J. Kaffka, Spectroscopy, 1995, 10, 46.
11. W. Plugge and C. van der Vlies, J. Pharm. Biomed Anal., 1996, 14, 891.
12. E. Dreassi, G. Ceramelli, L. Savini, P. Corti, P. L. Peruccio and S. Lonardi, Analyst, 1995, 120, 319.
13. E. Dreassi, G. Ceramelli and P. Corti, Analyst, 1995, 120, 1005.
14. E. Dreassi, G. Ceramelli, P. Corti, M. Massacesi and P. L. Perruccio, Analyst, 1995, 120, 2361.
15. D. J. Wargo and J. K. Drennen, J. Pharm. Biomed. Anal., 1996, 14, 1415.
16. R. A. Forbes, M. L. Persinger and D. R. Smith, J. Pharm. Biomed. Anal., 1996, 15, 315.
17. I. A. Cowe, J. W. McNicol and D. C. Cuthbertson, Analyst, 1989, 114, 683.
18. L. S. Aucott, P. H. Garthwaite and S. T. Buckland, Analyst, 1988, 113, 1849.
19. I. J. Barnes, M. S. Dhanoa and S. J. Lister, Appl. Spectrosc., 1989, 43, 772.
20. C. R. Bull, Analyst, 1991, 116, 781.
21. G. Kortum, Reflectance Spectroscopy, Principles, Methods, Applications, Springer-verlag, Berlin, 1969.
22. K. H. Norris and P. C. Williams, Cereal Chem., 1984, 61, 158.
23. A. J. O'Neil, R. D. Jee, R. A. Watt and A. C. Moffat, J. Pharm. Pharmacol., 1997, 49, Suppl. 4, 19.
24. J. L. Ilari, H. Martens and T. Isaksson, Appl. Spectrosc., 1988, 42, 722.
25. E. Ciurczak, P. Torlini and P. Demkowicz, Spectroscopy, 1986, 1, 36.
26. H. Mark, Principles and Practice of Spectroscopic Calibration, John Wiley & Sons Inc., New York, 1991.
27. J. C. Miller and J. N. Miller, Statistics For Analytical Chemistry, Ellis Horwood, New York, 3rd edn., 1993.
28. Handbook of Pharmaceutical Excipients, ed. A. Wade and P. J. Weller, American Pharmaceutical Association, Washington, The Pharmaceutical Press, London, 2nd edn., 1994.
29. S. Pearce, Manuf. Chem., 1986, 57, 77.