Co-administering clofazimine with infant formula enhances its oral bioavailability in rats and pigs

Milk-based formulations have been proposed as enabling formulations for the delivery of poorly water-soluble drugs to children due to their safety, dose versatility and ability to improve drug solubilisation through the digestion process. In this study the feasibility of using commercially available infant formula as an enabling formulation to enhance the solubilisation and oral bioavailability of clofazimine, a poorly soluble lipophilic drug, following oral administration was investigated. The solubilisation of crystalline clofazimine in digesting infant formula was assessed in vitro using synchrotron small-angle X-ray scattering. An in vivo pharmacokinetic study was then conducted to determine the oral bioavailability of a suspension of clofazimine in infant formula compared to a lipid-free aqueous suspension in both a rat and piglet animal model. Clofazimine administered in infant formula produced significantly higher plasma concentrations than the aqueous vehicle and resulted in comparable enhancements in relative oral bioavailability in both the piglet (235%) and rat animal models (256%). Results from this study demonstrated that infant formula was an effective enabling formulation, with a positive correlation between improved drug solubilisation during in vitro digestion of infant formula and enhanced in vivo drug exposure following oral administration. Infant formula therefore offers an inexpensive and scalable formulation approach for improving the bioavailability of paediatric drugs, like clofazimine, and enabling the treatment of infections in children.