Polymorphism and pharmacokinetic research of ribavirin / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish the preparation method and detection technology of ribavirin polymorphism, and to estimate the bioavailability differences among the ribavirin polymorphs. METHODS: Through polymorphism screening, ribavirin crystals of the form A, B, C, D were obtained. The crystal forms of ribavirin were characterized by different analysis methods, such as single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DCS), infrared spectrum method (IR) and melting point method (MP). solid ribavirin in different forms were orally administered to rats, and an HPLC-MS method was established to determine the plasma levels of ribavirin, and the bioavailability was analyzed. RESULTS: Of the four polymorphs of ribavirin, form C and form D were reported for the first time. The four polymorphic forms all could be identified by PXRD, DSC, IR and MP. The ρmax and AUC0-t of form A were superior to those of the other forms. CONCLUSION: Characteristic data for ribavirin polymorphism are obtained; and form A of ribavirin is a suitable medicinal crystal. This study has provided the basis for choice of medicinal crystal and the improvement of quality standards.