Factors affecting the apparent solubility of ursodeoxycholic acid in the grinding process

Ursodeoxycholic acid (UDCA) was ground by a vibrating mill. Apparent solubility of the ground sample was determined by Coulter counter method. The samples were characterized by pore size distribution measurement, powder X-ray diffraction (PXRD) measurement, near infra-red (NIR) spectroscopy and contact angle measurement. The dispersive and polar components of surface free energy were calculated from the contact angle data determined by a contact angle analyzer. Surface polarity was calculated from the surface free energy components. The apparent solubility of UDCA was increased by the grinding with vibrating mill, however, the particle size of ground sample was not decreased. An amorphization was observed in the PXRD pattern of the ground sample, and the crystallinity of sample was decreased with increasing the grinding time. During the initial grinding, the dispersive component of surface free energy was decreased, whereas the polar part of surface free energy was increased. The surface polarity of the sample was increased in the same manner. Relationship between the solubility and the factors changing in the grinding process was evaluated. There was a significant correlation between the apparent solubility and the surface polarity and crystallinity of the sample. The NIR spectra confirmed the appearance of [bond]OH group on the sample surface. The apparent solubility increase of the ground sample was closely related to the improvement of the surface polarity and the destruction of crystalline structure.