Chemometric Methods for the Quantification of Crystalline Tacrolimus in Solid Dispersion by Powder X‐Ray Diffractrometry

ABSTRACTThe objective of this study was to develop powder X‐ray diffraction (XRPD) chemometric model for quantifying crystalline tacrolimus from solid dispersion (SD). Three SDs (amorphous tacrolimus component) with varying drug to excipient ratios (24.4%, 6.7%, and 4.3% drug) were prepared. Placebo SDs were mixed with crystalline tacrolimus to make their composition equivalent to three SD (crystalline tacrolimus component). These two components were mixed to cover 0%–100% of crystalline drug. Uniformity of the sample mixtures was confirmed by near‐infrared chemical imaging. XRPD showed three distinct peaks of crystalline drug at 8.5°, 10.3°, and 11.2° (2θ), which were nonoverlapping with the excipients. Principal component regressions (PCR) and partial least square (PLS) regression used in model development showed high R2 (>0.99) for all the mixtures. Overall, the model showed low root mean square of standard error, standard error, and bias, which was smaller in PLS than PCR‐based model. Furthermore, the model performance was evaluated on the formulations with known percentage of crystalline drug. Model‐calculated crystalline drug percentage values were close to actual value. Therefore, these studies strongly suggest the application of chemometric‐XRPD models as a quality control tool to quantitatively predict the crystalline drug in the formulation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2819–2828, 2014