Solid dispersions of dihydroartemisinin in polyvinylpyrrolidone

Abstract

In the present study the physicochemical characteristics of dihydroartemisinin, polyvinylpyrrolidone and their solid dispersions were evaluated at various proportions of drug and polyvinylpyrrolidone. These properties were investigated with X-ray diffraction, fourier transform infrared spectrophotometry, differential scanning calorimetry, equilibrium solubility at twenty five and thirty seven degree centigrade. X-ray diffraction analysis detected that dihydroartemisinin became more amorphous as drug carrier ratio was enhanced in solid dispersions. Fourier transform infrared spectra suggested that there was a hydrogen bonding interaction between dihydroartemisinin and polyvinylpyrrolidone in all solid dispersions. These interactions reflected the changes in crystalline structures of dihydroartemisinin. The thermal behavior of dihydroartemisinin was unusual as it exhibited melting exotherm instead of endotherm. In solid dispersions containing varying contents of polyvinylpyrrolidone, enthalpy change and peak area were enhanced while melting onset temperature decreased with increase in polyvinylpyrrolidone proportion. This was attributed to a solid-state interaction. Equilibrium solubility of dihydroartemisinin increased sixty-fold due to induction of polyvinylpyrrolidone. When this solubility was compared among thirty-seven and twenty five degree centigrade in solid dispersions, it was up to seven times more at higher temperature. Physicochemical characteristics of solid dispersions containing drug carrier ratio of one: nine prepared in acetonitrile, ethanol, methanol and tetrahydrofuran showed differences which indicated that properties of medium i.e. dielectric constant, dipole moment and structure, influenced the amount of amorphousness and related properties of dihydroartemisinin.