title: Near-infrared and fourier transform infrared chemometric methods for the quantification of crystalline tacrolimus from sustained-release amorphous solid dispersion.
abstract: The objective of the present research was to study the feasibility of using near-infrared (NIR) and Fourier transform infrared (FTIR)-based chemometric models in quantifying crystalline and amorphous tacrolimus from its sustained-release amorphous solid dispersion (ASD). ASD contained ethyl cellulose, hydroxypropyl methyl cellulose, and lactose monohydrate as carriers, and amorphous form of tacrolimus in it was confirmed by X-ray powder diffraction. Crystalline physical mixture was mixed with ASD in various proportions to prepare sample matrices containing 0%-100% amorphous/crystalline tacrolimus. NIR and FTIR of the samples were recorded, and data were mathematically pretreated using multiple scattering correction, standard normal variate, or Savitzky-Golay before multivariate analysis, partial-least-square regression (PLSR), and principle component regression (PCR). The PLSR models were more accurate than PCR for NIR and FTIR data as indicated by low value of root-mean-squared error of prediction, standard error of prediction and bias, and high value of R(2). Additionally, NIR data-based models were more accurate and precise than FTIR data models. In conclusion, NIR chemometric models provide simple and fast method to quantitate crystalline tacrolimus in the ASD formulation.
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Akhtar
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Srikant
authors.initials: S
authors.lastname: Bykadi
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D003460:Crystallization; D003692:Delayed-Action Preparations / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry*; D016018:Least-Squares Analysis; D025341:Principal Component Analysis; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D016559:Tacrolimus / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: amorphous; chemometrics; crystallinity; infrared spectroscopy; near-infrared spectroscopy; partial least squares; principal component analysis; solid dispersion