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Formulation analyses of high-volume prescription drugs

  • T.G. Fawcett (a1), S. Gates-Rector (a1), A.M. Gindhart (a1), M. Rost (a1), S.N. Kabekkodu (a1), J. R. Blanton (a1) and T. N. Blanton (a1)...

Abstract

A collection of 65 formulated tablets and capsules were analyzed for phase composition by full pattern matching powder diffraction methods. The collection contained 32 of the top 200 prescription drugs sold in 2016 as well as many high-volume prescriptions and over the counter drugs from prior years. The study was used to evaluate new methods of analysis as well as the efficacy of programs designed to collect references on high volume excipients and pharmaceuticals for inclusion in the Powder Diffraction File. The use of full pattern matching methods as well as reference pattern additions of many common excipients enabled major phase excipient identification in all formulations. This included identification of crystalline, nanocrystalline, and amorphous ingredients because full pattern matching involved the use of characteristic coherent and incoherent scatter. Oftentimes identification of the major excipients significantly aided the clean identification of the active pharmaceutical ingredients (APIs) and their polymorphic form, even at low concentrations (1–10 wt. %). Overall 93% of the APIs were identified, most through a PDF® material reference, but also through patent cross-referencing and similarity analysis comparisons.

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a)Author to whom correspondence should be addressed. Electronic mail: dxcfawcett@outlook.com

References

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Aher, U. P., Tarur, V. R., Sathe, D. G., Naidu, A. V., and Sawant, K. D. (2007). “Polymorph of (1-benzyl-4-[(5,6-dimethoxy-1-indanone)-2-y1] methyl piperidine hydrochloride (Donepezil hydrochloride) and a process for producing thereof,” US Patent 7,186,842.
Barr, G., Dong, W., and Gilmore, C. J. (2004a). “High throughput powder diffraction. II. Applications of clustering methods and multivariate data analysis,” J. Appl. Cryst. 37, 243252.
Barr, G., Dong, W., Gilmore, C. J., and Faber, J. (2004b). “High throughput powder diffraction. III. The application of full profile pattern matching and multivariate statistical analysis to round robin type data sets,” J. Appl. Cryst. 37, 635642.
Billinge, S. J. L. (2011). Total Scattering Pair Distribution Functions (TSPDF) for Fingerprinting Amorphous Pharmaceuticals. presented at PPXRD-10, 16-19 May 2011, Lyon, France. Full presentation available for free download at http://www.icdd.com/assets/ppxrd/presentations/10/PPXRD-10_Simon_Billinge.pdf.
Blanton, T. N. (2013). Eastman Kodak Co., Rochester, NY private communication, powder diffraction analyses of gelatins, includes the publication of gelatin references PDF#’s 00-064-1605, 00-064-1606 and 00-064-1607.
Faber, J. and Blanton, J. (2008). Full Pattern Comparisons of Experimental and Calculated Powder Patterns Using the Integral Index Method in PDF-4+. Adv. X-ray Anal., 51, 183-189. (These same two authors developed a normalization of the integral index (normalized R-index) that was published in PDF database products starting with Release 2011).
Fawcett, T. G., Faber, J., and Hubbard, C. R. (2004). “Formulation Analysis of Off-the-Shelf Pharmaceuticals,” Am. Pharm. Rev. 7(3), 80–83.
Fawcett, T. G., Faber, J., Needham, F., Kabekkodu, S. N., Hubbard, C. R., and Kaduk, J. A. (2006). “Developments in formulation analyses by powder diffraction analysis,” Powd. Diff. 21(2), 105110.
Fawcett, T. G., Crowder, C. E., Kabekkodu, S. N., Needham, F., Kaduk, J. A., Blanton, T. N., Petkov, V., Bucher, E., and Shpanchenko, R. (2013). “Reference materials for the study of polymorphism and crystallinity in cellulosics,” Powd. Diff. 28(1), 1831.
Fawcett, T. G., Kabekkodu, S. N., Blanton, J. R., Crowder, C. E., and Blanton, T. N. (2015a). ““Simulation tools and references for the analysis of nanomaterials,” Adv. X-Ray Anal. 58, 108120.
Fawcett, T. G., Kabekkodu, S. N., Zhong, K., Gindhart, A. M., Blanton, J. R., and Blanton, T. N. (2015b). Analyzing amorphous and nanocrystalline materials by full pattern analysis. presented at PPXRD-13, 18–21 May 2015, Bad Herranalb, Germany. Full presentation available for free download at http://www.icdd.com/assets/ppxrd/presentations/13/PPXRD-13-Fawcett.pdf
Fawcett, T. G., Kabekkodu, S. N., Gates-Rector, S., Gindhart, A. M., Blanton, J. R., and Blanton, T. N. (2016). The Analysis of Non-Crystalline Materials in Pharmaceutical Formulations. presented at PPXRD-14, Sanibel Harbor Marriott, Fort Myers, Florida, USA.
Fawcett, T. G., Kabekkodu, S. N., Blanton, J. R., and Blanton, T. N. (2017). “Chemical analysis by diffraction: the powder diffraction file™,” Powd. Diff. 32(2), 6371.
Fawcett, T. G., Gates-Rector, S., Gindhart, A. M., Rost, M., Kabekkodu, S. N., Blanton, J. R., and Blanton, T. N. (2019). “A practical guide to pharmaceutical analyses using X-ray powder diffraction,” Powd. Diffr. (in press).
Gates, S. D., Blanton, T. N., and Fawcett, T. G. (2014). “A new” chain” of events: polymers in the powder diffraction file™ (PDF ®),” Powd. Diff. 29(2), 102107.
Gates-Rector, S., Blanton, T. N., Gindhart, A. M., and Kaduk, J. A. (2018). Crystal Structure Determination and Phase Identification of Pharmaceutical Material(s) Using Powder Diffraction Techniques. Poster presentation ICDD Spring Meeting, 2018, Newtown Square, PA, USA.
Hu, X., Fang, H., Feng, J., and Jianyue, G. (2012). “Novel crystalline form of benazepril hydrochloride and preparation method of crystalline form,” patent CN103012267B, assigned to Zhejiang University.
International Centre for Diffraction Data (2014a). Technical Bulletin, PDF-4/Organics,” published by the ICDD. Nano material examples for apatite and Lipitor given in the case histories. Available for free download at http://www.icdd.com//wp-content/uploads/2018/03/PDF-4_Organics_Technical_Bulletin.pdf
International Centre for Diffraction Data (2014b). Technical Bulletin, Search and Identify with SIeve/SIeve+,” published by the ICDD. Available for free download at http://www.icdd.com//wp-content/uploads/2018/03/SIeve-Technical-Bulletin.pdf
International Centre for Diffraction Data (2017). PDF-4+2018 (Database), edited by Dr. Soorya Kabekkodu, International Centre for Diffraction Data, Newtown Square, PA, USA.
International Pharmaceutical Excipient Council (IPEC) America (2018). Most commonly used excipients in U.S.-manufactured drug products. http://ipecamericas.org/what-ipec-americas/faqs
Kaduk, J. A. (2019). Chapter 3.7, “Crystallographic databases and powder diffraction,” in International Tables for Crystallography, Volume H, Powder Diffraction, edited by Gilmore, C., Kaduk, J. A., and Schenk, H. (John Wiley & Sons, New York), Wiley IUCr series, pp. 304324.
Kaduk, J. A., Crowder, C. E., Zhong, K., Fawcett, T. G., and Suchomel, M. R. (2014). “Crystal structure of atomoxetine hydrochloride (strattera), C17H22NOCl,” Powder Diffr. 29(3), 269273.
Kaduk, J. A., Wheatley, A. M., Gindhart, A. M., and Blanton, T. N. (2018). “Crystal structures of large volume commercial pharmaceuticals,” poster presentation ICDD Spring Meeting, 2018, Newtown Square, PA, USA.
Madsen, I., Scarlett, N., Kleeberg, R., and Knorr, K. (2019). Chapter 3.9, “Quantitative Phase Analysis,” in International Tables for Crystallography, Volume H, Powder Diffraction, edited by Gilmore, C., Kaduk, J. A., and Schenk, H. (John Wiley & Sons, New York), Wiley IUCr series, pp. 344372.
McGrath, N. A., Brichacek, M., and Njardarson, J. T. (2010). “A graphical journey of innovative organic architectures that have improved our lives,J. Chem. Ed., 87, 1348, updated charts available at http://njardarson.lab.arizona.edu/content/top-pharmaceuticals-poster
Mendoza, J. H. Q., Henao, J. A., Aparicio, A. P., and Bohorquez, A. R. R. (2017). “X-ray powder diffraction data and characterization of Mirabegron,” Powd. Diff. 32(4), 290294.
Murakami, N. (2006). Crystalline form of 1- (delta-D-glucopyranosyl) 4 -methyl- 3- [5- (4 –fluorophenyl) 2-thienylmethyl] benzene hemihydrate,” patent CN101573368B assigned to Mitsubishi Tanabe Pharmaceutical Co., Ltd.
Petkov, V., Ren, Y., Kabekkodu, S., and Murphy, D. (2013). “Atomic pair distribution functions analysis of disordered low-Z materials,” P. Chem. Chem. Phys. 22, 85448554.
Qiu, J., Li, G., Sheng, Y., and Zhu, M. (2015). “Quantification of febuxostat polymorphs using X-ray diffraction technique,” J. Pharm. Biomed. Anal. 107, 298303.
Rowe, R. C., Sheshkey, P. J., and Quinn, M. E. (Eds.) (2009). Handbook of Pharmaceutical Excipients, Sixth Edition (Pharmaceutical Press, London, England), pp. 728731.
Scardi, P., Leoni, M., Lamas, D. G., and Cabanillas, E. D. (2005). “Grain size distribution of nanocrystalline systems,” Powd. Diff. 20(4), 353358.
Scardi, P., Leoni, M., and Faber, J. (2006). “Diffraction line profile from a disperse system: a simple alternative to voightian profiles,” Powd. Diff. 21(4), 270.
Teng, J., Bates, S., Engers, D., Leach, K., Schields, P., and Yang, Y. (2010). “Effect of water vapor sorption on local structure of poly(vinylpyrrolidone),” J. Pharm. Sci. 99, 38153825.
United States, Code of Federal Regulations, Title 21, Vol 4, 21CFR201.10 (2017).“Food and Drugs, Subchapter C – Drugs General, Part 201 – Labelling.
Whitfield, P. S., Huq, A., and Kaduk, J. A. (2019). Chapter 2.10, “Specimen preparation,” in International Tables for Crystallography, Volume H, Powder Diffraction, edited by Gilmore, C., Kaduk, J. A., and Schenk, H. (John Wiley & Sons, New York), Wiley IUCr series, pp. 200222.
Zeng, X., Wang, Q., Xiong, X. N., Du, Q. H., and Lia, H. (2017). “X-ray powder diffraction data for alogliptin benzoate, C18H21N5O2·C7H6O2,” Powd. Diff. 32(1), 4952.

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Formulation analyses of high-volume prescription drugs

  • T.G. Fawcett (a1), S. Gates-Rector (a1), A.M. Gindhart (a1), M. Rost (a1), S.N. Kabekkodu (a1), J. R. Blanton (a1) and T. N. Blanton (a1)...

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