Gamma-scintigraphy as a novel method to study the distribution and retention of a bioadhesive vaginal delivery system in sheep

The distribution and the retention time of a novel bioadhesive intravaginal delivery system based on HYAFF microspheres were studied in a sheep model. In a preliminary experiment, the vagina of the ewe was outlined by gamma scintigraphy following vaginal administration of a radiolabelled gel and this data was used as a reference for subsequent evaluation of the distribution of bioadhesive vaginal formulations. Technetium-labelled HYAFF microspheres were administered intravaginally, either as a dry powder or suspended in a vaginal pessary, and the intensity and distribution of radioactivity in the genital tract was determined for a period of 12 h. With both HYAFF formulations, the radiolabelled microspheres were dispersed along the length of the vagina and were retained at this site for the duration of the study. Twelve hours after administration, between 60 and 80% of the radioactivity remained within the vagina with retention of the microspheres being slightly higher for the dry powder formulation than for the vaginal pessary. Importantly, there was no indication of movement of the microspheres from the vagina to the upper levels of the genital tract. These studies further demonstrated the potential of HYAFF microspheres as a long-acting intravaginal delivery system and illustrated the utility of the sheep model and the gamma-scintigraphy methodology for a direct assessment of the distribution, spreading and retention time of bioadhesive formulations.