Determination of the main solid-state form of albendazole in bulk drug, employing Raman spectroscopy coupled to multivariate analysis

Abstract

Albendazole (ALB) is a broad-spectrum anthelmintic, which exhibits two solid-state forms (Forms I and II). The Form I is the metastable crystal at room temperature, while Form II is the stable one. Because the drug has poor aqueous solubility and Form II is less soluble than Form I, it is desirable to have a method to assess the solid-state form of the drug employed for manufacturing purposes. Therefore, a Partial Least Squares (PLS) model was developed for the determination of Form I of ALB in its mixtures with Form II. For model development, both solid-state forms of ALB were prepared and characterized by microscopic (optical and with normal and polarized light), thermal (DSC) and spectroscopic (ATR-FTIR, Raman) techniques. Mixtures of solids in different ratios were prepared by weighing and mechanical mixing of the components. Their Raman spectra were acquired, and subjected to peak smoothing, normalization, standard normal variate correction and de-trending, before performing the PLS calculations. The optimal spectral region (1396–1280 cm−1) and number of latent variables (LV = 3) were obtained employing a moving window of variable size strategy. The method was internally validated by means of the leave one out procedure, providing satisfactory statistics (r2 = 0.9729 and RMSD = 5.6%) and figures of merit (LOD = 9.4% and MDDC = 1.4). Furthermore, the method’s performance was also evaluated by analysis of two validation sets. Validation set I was used for assessment of linearity and range and Validation set II, to demonstrate accuracy and precision (Recovery = 101.4% and RSD = 2.8%). Additionally, a third set of spiked commercial samples was evaluated, exhibiting excellent recoveries (94.2 ± 6.4%). The results suggest that the combination of Raman spectroscopy with multivariate analysis could be applied to the assessment of the main crystal form and its quantitation in samples of ALB bulk drug, in the routine quality control laboratory.