Drugs with pH-dependent solubility that have poor water solubility can be identified in the drug discovery pipeline. Some of them have poor oral absorption, which can result in insufficient efficacy. Micro-environmental pH-modifying solid dispersion (micro pHm SD) is a promising approach to overcome the poor oral absorption of these drugs. In the present study, toltrazuril (TOL), a weakly acidic drug with poor aqueous and pH-dependent solubility, was used as a model drug. Using micro pHm SD, a novel oral oil-based suspension of TOL SD (TSDS) was developed, and the stability of this formulation was evaluated based on particle size, settling volume ratio, redispersibility, thermal stability, and drug content. The optimized soybean oil-based TSDS (S-TSDS) had high physicochemical stability and good histocompatibility with common inflammatory reactions. The results of the in vitro dissolution analysis showed that S-TSDS rapidly and markedly released the drug and provided higher efficacy and longer persistence against coccidiosis (above 90.9%) in rabbits. This technique could increase the oral absorption and bioavailability of new drug candidates.
Keywords: micro-environmental pH-modifying; oral; solid dispersion; suspension; toltrazuril.