Quantification of clarithromycin polymorphs in presence of tablet excipients
Characterization of solid form of API in presence of excipients offers considerable challenge. Aim of the present study was to quantify polymorphs of clarithromycin (CAM) in a commercial tablet in the presence of excipients, by powder X-ray diffraction (PXRD) method. Polymorphic Form I (CAM-1), Form II (CAM-2) and amorphous phase of CAM were characterized using thermal and crystallographic tools. CAM-1 and CAM-2 were found to be monotropically related, with CAM-2 being the stable form. PXRD instrument related parameters were optimized for characterization of CAM polymorphic forms in a mixture of excipients. Calibration curves for CAM-1 and CAM-2 were prepared in a mixture with excipients. Analytical method based on differences in diffraction pattern of CAM-1, CAM-2 and excipients was developed. Sodium methyl paraben, sodium propyl paraben, microcrystalline cellulose and magnesium stearate were crystalline and exhibited characteristic diffraction pattern. Starch, croscarmellose sodium, talc and sodium starch glycolate were found to be semicrystalline in nature while colloidal silicon dioxide was amorphous material. Diffraction peak at 8.7° 2θ value allowed quantification of CAM-2 in the presence of excipients. The analytical method was evaluated and validated for accuracy, precision, inter and intraday variation, variability due to sample repacking and instrument reproducibility. The method for quantification of CAM-2 in the range of 80 to 100% w/w was found to be linear with R2 = 0.998. Relative standard deviation (RSD) due to sample repacking was 2.77% indicating good homogeneity of mixing of samples. RSD due to all assay errors was found to be 1.66%. PXRD analysis of commercial tablet revealed presence of CAM-2 as major polymorph and it was found to be 98% of the overall content of API. CAM-1 was found to be present as an impurity in trace amount as evidenced by peaks at 2θ values of 5.2° and 6.7°. This method allows characterization of polymorphic forms of CAM in presence of common tablet excipients. It can be a useful tool for monitoring solid form behavior during product development and stability studies.