Hydrogen bond replacement--unearthing a novel molecular mechanism of surface solid dispersion for enhanced solubility...

The project was aimed to enhance the solubility of ivermectin using surface solid dispersion (SSD), elucidate the mechanism of drug release and to develop its tablet that can draw rapid clinical effects on dogs for controlling Ascaris parasites. Superdisintegrants and adsorbents were used to formulate SSDs by co-evaporation method. Formulation 9th that constituted from drug:aerosil (1:10) was selected after solubility and in vitro dissolution evaluation, and characterized by DSC, XRPD, DRS and SEM analysis. In vitro evaluation and in vivo efficacy of its tablet on dogs (fecal egg and tick counting studies) were compared with marketed tablets. This formulation enhanced the solubility of ivermectin to 456.25±1.70% and released 93.55±0.47% in 60 min. DRS spectral analysis unearthed a novel molecular mechanism of hydrogen bond replacement that drifts the drug into the medium from the surface of the SSD particles. Reduced crystallinity was confirmed by XRPD and supported by SEM. During in vitro and in vivo studies, the formulated tablet showed superiority over marketed tablet with higher parasite inhibition (p<0.001). Thus SSD is a promising technique for enhancing IVM solubility at molecular level enabling its rapid oral delivery to control endo- as well as ectoparasites for veterinary purpose.