A novel oil-based suspension of a micro-environmental, pH-modifying solid dispersion for parenteral delivery: Formulation and stability evaluation

The objective of this study was to evaluate a novel oil-based suspension as a potential parenteral drug delivery system for drugs with poor water solubility. Most of the new active pharmaceutical ingredients are weak acid or basic drugs with pH-dependent solubility. To limit this dependence, use of micro-environmental pH-modifying solid dispersions (micro pHm SD) has been proved to increase the bioavailability of these drugs. Toltrazuril (TOL), a weakly acidic drug with poor aqueous and pH-dependent solubility, was studied as a model drug. Recently, studies on TOL with focus on the parenteral injection are rarely to find in the literature. A novel parenteral oil-based TOL suspension was prepared containing TOL micro pHm SD (TSD) powders suspended in oil-based vehicles and the optimal formulation was screened. The stability of this formulation was assessed considering particle size distribution, settling volume ratio, redispersibility, thermal stability, and drug content. The optimized white oil-based TOL pHm SD suspension (W-TSDS) showed significant improved stability and shear-thinning behavior. In particular, fumed silica as suspending agent positively influenced the physical stability of the formulation. Furthermore, W-TSDS showed good injectability using 21 G needles and more rapid and sustained drug release compared to TSD powders in vitro. In the in vivo safety evaluation, W-TSDS showed good histocompatibility in rabbits injected subcutaneously or intramuscularly. We believe these findings provide an alternative choice of dosage form for the delivery of new active pharmaceutical ingredients.