Polymorphic transformation of chlortetracycline hydrochloride crystals studied by infrared spectrophotometric method.

Abstract

A quantitative method was described which utilized IR spectroscopy for the determination of chlortetracycline hydrochloride (CTC-HCl) crystalline forms in mixtures. Data were included which demonstrated that the method could be utilized to follow the rate of transformation taking place in the biologically available crystalline form (.beta. form). Transformation of the crystalline form under different conditions such as solid state and aqueous suspension was investigated. The solid CTC-HCl .beta. form changed to the more stable .alpha. form in high humidities, over 75% relative humidity (R.H.) at 20.degree. C. The rate of transformation was proportional to the humidity. Under 65% R.H., no polymorphic transformation was observed for 40 days at 20.degree. C. Transformation of the .beta. form was also not delected by heating at 70.degree. C. In aqueous suspensions, rapid solution phase transformation was observed from the CTC-HCl .beta. form to the water-stable .alpha. form. The rate of transformation in the suspensions was temperature and pH dependent. Results obtained from these transformation studies suggested that water and water vapor were important factors in the transformation of the CTC-HCl .beta. form.