A Kinetic Study of the Polymorphic Transformation of Nimodipine and Indomethacin during High Shear Granulation

Abstract

Abstract. The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a twodimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol −1 from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.

Comparison of Univariate and Multivariate Models of 13C SSNMR and XRPD Techniques for Quantification of Nimodipine Polymorphs

“…1b). These observations were in concurrence with reported values (17,(22)(23)(24). Furthermore, the sample matrices that contained varying percentage of form I and form II showed the peaks of both the polymorphs (Fig.…”

“…The purchased nimodipine was form I, and form II was prepared according to the method reported in a literature (17). Nimodipine form I was dissolved in ethanol and the solvent was allowed to evaporate to dryness.…”

Chemometric Evaluation of Near Infrared, Fourier Transform Infrared, and Raman Spectroscopic Models for the Prediction of Nimodipine Polymorphs

“…Nimodipine Mod II was prepared by method described elsewhere . Briefly drug (Mod I) was dissolved in ethanol and allowed the solvent to evaporate to dryness.…”

Evaluation of degradation kinetics and physicochemical stability of tenofovir

“…The significance of the E a value is to determine the temperature dependency of a chemical reaction. The higher the value of E a for a chemical reaction the greater the acceleration with increase in temperature and the more the stability of a drug is temperature dependent . Generally, drugs with lower E a values have significantly longer shelf‐lives .…”

“…The higher the value of E a for a chemical reaction the greater the acceleration with increase in temperature and the more the stability of a drug is temperature dependent. [34,35] Generally, drugs with lower E a values have significantly longer shelf-lives. [34] The rate constant (k' 25 ) that corresponds to room temperature (25°C) was calculated from the regression equation.…”