TY - JOUR

T1 - Quantitative analysis of polymorphic mixtures of ranitidine hydrochloride by raman spectroscopy and principal components analysis

AU - Pratiwi, Destari

AU - Paul Fawcett, J.

AU - Gordon, Keith C.

AU - Rades, Thomas

PY - 2002/11

Y1 - 2002/11

N2 - Ranitidine hydrochloride exists as two polymorphs, forms I and II, both of which are used to manufacture commercial tablets. Raman spectroscopy can be used to differentiate the two forms but univariate methods of quantitative analysis of one polymorph as an impurity in the other lack sensitivity. We have applied principal components analysis (PCA) of Raman spectra to binary mixtures of the two polymorphs and to binary mixtures prepared by adding one polymorph to powdered tablets of the other. Based on absorption measurements of seven spectral regions, it was found that >97% of the spectral variation was accounted for by three principal components. Quantitative calibration models generated by multiple linear regression predicted a detection limit and quantitation limit for either forms I or II in mixtures of the two of 0.6 and 1.8%, respectively. This study demonstrates that PCA of Raman spectroscopic data provides a sensitive method for the quantitative analysis of polymorphic impurities of drugs in commercial tablets with a quantitation limit of less than 2%.

AB - Ranitidine hydrochloride exists as two polymorphs, forms I and II, both of which are used to manufacture commercial tablets. Raman spectroscopy can be used to differentiate the two forms but univariate methods of quantitative analysis of one polymorph as an impurity in the other lack sensitivity. We have applied principal components analysis (PCA) of Raman spectra to binary mixtures of the two polymorphs and to binary mixtures prepared by adding one polymorph to powdered tablets of the other. Based on absorption measurements of seven spectral regions, it was found that >97% of the spectral variation was accounted for by three principal components. Quantitative calibration models generated by multiple linear regression predicted a detection limit and quantitation limit for either forms I or II in mixtures of the two of 0.6 and 1.8%, respectively. This study demonstrates that PCA of Raman spectroscopic data provides a sensitive method for the quantitative analysis of polymorphic impurities of drugs in commercial tablets with a quantitation limit of less than 2%.

KW - Polymorphism

KW - Principal components analysis

KW - Quantitative analysis

KW - Raman spectroscopy

KW - Ranitidine-HCl

UR - http://www.scopus.com/inward/record.url?scp=0036848589&partnerID=8YFLogxK

U2 - 10.1016/S0939-6411(02)00113-3

DO - 10.1016/S0939-6411(02)00113-3

M3 - Journal article

C2 - 12445565

AN - SCOPUS:0036848589

VL - 54

SP - 337

EP - 341

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 3

ER -