Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2003 June; 4(2): 58–69.
Published online 2003 March 19. doi:  10.1208/pt040219
PMCID: PMC2750597

Comparative determination of polymorphs of indomethacin in powders and tablets by chemometrical near-infrared spectroscopy and X-ray powder diffractometry


The purpose of this research was to develop a rapid chemometrical method based on near-infrared (NIR) spectroscopy to determine indomethacin (IMC) polymorphic content in mixed pharmaceutical powder and tablets. Mixed powder samples with known polymorphic contents of forms α and γ were obtained from physical mixing of 50% of IMC standard polymorphic sample and 50% of excipient mixed powder sample consisting of lactose, corn starch, and hydroxypropyl-cellulose. The tablets were obtained by compressing the mixed powder at 245 MPa. X-ray powder diffraction profiles and NIR spectra were recorded for 6 kinds of standard materials with various polymorphic contents. The principal component regression analysis was performed based on normalized NIR spectra sets of mixed powder standard samples and tablets. The relationships between the actual and predicted polymorphic contents of form g in the mixed powder measured using x-ray powder diffraction and NIR spectroscopy show a straight line with a slope of 0.960 and 0.995, and correlation coefficient constants of 0.970 and 0.993, respectively. The predicted content values of unknown samples by x-ray powder diffraction and NIR spectroscopy were reproducible and in close agreement, but those by NIR spectroscopy had smaller SDs than those by x-ray powder diffraction. The results suggest that NIR spectroscopy provides a more accurate quantitative analysis of polymorphic content in pharmaceutical mixed powder and tablets than does conventional x-ray powder diffractometry.

Full Text

The Full Text of this article is available as a PDF (397K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. FDA Papers. Guidelines: manufacturing and controls for INDs and NDAs. Pharm Tech Japan. 1985;1:835–850.
2. Haleblian JK. Characterization of habits and crystalline modification of solids and their pharmaceutical applications. J Pharm Sci. 1975;64:1269–1288. doi: 10.1002/jps.2600640805. [PubMed] [Cross Ref]
3. Otsuka M, Matsuda Y. Polymorphism, pharmaceutical aspects. In: Swarbrick J, Boylan JC, editors. Encyclopedias of Pharmaceutical Technology. Vol 12. New York, NY: Marcel Dekker; 1995. pp. 305–326.
4. Yoshino H, Hagiwara Y, Kobayashi S, Samejima M. Estimation of polymorphic transformation degree of pharmaceutical raw materials. Chem Pharm Bull. 1984;32:1523–1536.
5. Kaneniwa N, Otsuka M, Hayashi T. Physicochemical characterization of indomethacin polymorphs and the transformation kinetics in ethanol. Chem Pharm Bull. 1985;33:3447–3455. [PubMed]
6. Ahmed H, Buckton G, Rawlins DA. The use of isothermal microcalorimetry in the study of small degree of amorphous content of a hydrophobic powder. Int J Pharm. 1996;130:195–201. doi: 10.1016/0378-5173(95)04288-1. [Cross Ref]
7. Black DB, Lovering EG. Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods. J Pharm Pharmacol. 1977;29:684–687. [PubMed]
8. Taylor LS, Zografi G. The quantitative analysis of crystallinity using FT-raman spectroscopy. Pharm Res. 1998;15:755–761. doi: 10.1023/A:1011979221685. [PubMed] [Cross Ref]
9. Berridge JC, Jones P, Roberts-McIntosh AS. Chemometrics in pharmaceutical analysis. J Pharm Biomed Anal. 1991;9:597–604. doi: 10.1016/0731-7085(91)80184-B. [PubMed] [Cross Ref]
10. Edlund U, Grahn H. Multivariate data analysis of NMR data. J Pharm Biomed. Anal. 1991;9:655–658. doi: 10.1016/0731-7085(91)80191-B. [PubMed] [Cross Ref]
11. Lincoln D, Fell AF, Anderson NH, England D. Assessment of chromatographic peak purity of drugs by multivariate analysis of diode-array and mass spectrometric data. J Pharm Biomed Anal. 1992;10:837–844. doi: 10.1016/0731-7085(91)80089-R. [PubMed] [Cross Ref]
12. Otsuka M, Kato F, Matsuda Y. Comparative evaluation of the degree of indomethacin crystallinity by chemoinfometrical Fourier-transformed near-infrared spectroscopy and conventional powder X-ray diffractometry. Pharm Sci. 2000;2:9–9. [PMC free article] [PubMed]
13. Morisseau KM, Rhodes CT. Near-infrared spectroscopy as a nondestructive alternative to conventional tablet hardness testing. Pharm Res. 1997;14:108–111. doi: 10.1023/A:1012071904673. [PubMed] [Cross Ref]
14. Drennen JK, Lodder RA. Nondestructive near-infrared analysis of intact tablets for determination of degradation products. J Pharm Sci. 1990;79:622–627. doi: 10.1002/jps.2600790717. [PubMed] [Cross Ref]
15. Buchanan BR, Baxter MA, Chen TS, Qin XZ, Robinson PA. Use of near-infrared spectroscopy to evaluate an active in a filmcoated tablet. Pharm Res. 1996;13:616–621. doi: 10.1023/A:1016014625418. [PubMed] [Cross Ref]
16. Frake P, Gill I, Luscombe CN, Rudd DR, Waterhouse J, Jayasooriya UA. Near-infrared mass median particle size determination of lactose monohydrate, evaluating several chemometric approaches. Analyst. 1998;123:2043–2046. doi: 10.1039/a802532k. [PubMed] [Cross Ref]
17. Martents H, Næs T. Multivariate Calibration. New York, NY: John Wiley & Sons; 1989.
18. Norris T, Aldridge PK, Sekulic SS. Determination of endpoints for polymorph conversions of crystalline organic compounds using on-line near-infrared spectroscopy. Analyst. 1997;122:549–552. doi: 10.1039/a700782e. [Cross Ref]
19. Saver RW, Meulman PA, Bowerman DK, Havens JL. Factor analysis of infrared spectra for solid-state forms of delavirdine mesylate. Int J Pharm. 1998;167:105–120. doi: 10.1016/S0378-5173(98)00051-9. [Cross Ref]
20. Patel AD, Luner PE, Kemper MS. Low-level determination of polymorph composition in physical mixtures by near-infrared reflectance spectroscopy. J Pharm Sci. 2001;90:360–370. doi: 10.1002/1520-6017(200103)90:3<360::AID-JPS11>3.0.CO;2-U. [PubMed] [Cross Ref]
21. Otsuka M, Kato F, Matsuda Y. Determination of indomethacin polymorphic contents by chemometric near-infrared spectroscopy and conventional powder X-ray diffractometry. Analyst. 2001;126:1578–1582. doi: 10.1039/b103498g. [PubMed] [Cross Ref]
22. Blanco M, Villar A. Polymorphic analysis of a pharmaceutical preparation by NIR spectroscopy. Analyst. 2000;125:2311–2314. doi: 10.1039/b005746k. [PubMed] [Cross Ref]
23. Patel AD, Luner PE, Kemper MS. Quantitative analysis of polymorphs in binary and multi-component powder mixtures by near-infrared reflectance spectroscopy. Int J Pharm. 2000;206:63–74. doi: 10.1016/S0378-5173(00)00530-5. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists