Effects of solvents in film-coating dispersion on the solid state transformation of olanzapine in coated tablets

Abstract

Anhydrous olanzapine Form I powder was exposed to water or ethanol or mixtures thereof, and analyzed by polarized light microscopy, X-ray powder diffractrometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Raman spectroscopy (Raman) using Principal Component Analysis (PCA). It was found that conversion of Form I to Form B required high amount of water, while Form I can be easily transformed to EtOH-H2O mixed solvate by using only minute amount of ethanol. In addition, temperatures of 25°C, 40°C and 70°C and compression forces of 1000 psi, 2000 psi and 3000 psi had no effect on olanzapine solid state transformation.

Form I core tablets were coated with film coating dispersions by spray gun and dried at 25°C, 40°C and 70°C for 3 hours. It was found that only PCA method, obtained from Raman spectra within ranges of 2950 to 2750 cm-1, 1500 to 1400 cm-1, 1100 to 800 cm-1, 700 to 600 cm-1 and 200 to 150 cm-1 was able to differentiate between forms. The slow evaporation rate at 25 °C and 40 °C of water or ethanol in film-coating dispersion from Form I core tablets will induce conversion to Form B or EtOH-H2O mixed solvate, respectively. However, no change was observed when fast evaporation rate at 70 °C was used. Results suggest that the control of optimal quantity and rate of evaporation for film-coating dispersion during pharmaceutical manufacturing of olanzapine coated tablets are critical in maintaining the original Form I solid state form.