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Chemometric methods for the quantification of crystalline tacrolimus in solid dispersion by powder X-ray diffractrometry.

Journal of pharmaceutical sciences (2014-03-04)
Akhtar Siddiqui, Ziyaur Rahman, Srikant Bykadi, Mansoor A Khan
ABSTRACT

The 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 R(2) (>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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Lactose (Monohydrate), Pharmaceutical Secondary Standard; Certified Reference Material
USP
Lactose monohydrate, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
D-Lactose monohydrate, ACS reagent
Sigma-Aldrich
D-Lactose monohydrate, ≥98.0% (HPLC)
Sigma-Aldrich
D-Lactose monohydrate, BioUltra, ≥99.5% (HPLC)
Sigma-Aldrich
D-Lactose monohydrate, tested according to Ph. Eur.