Characteristics of asymmetric microcrystalline solidification pellets and a better prediction for bioequiavailability...

Controlled release of poorly soluble drugs and the impact of solubilization on in vivo oral absorption remain pivotal concerns in pharmaceutical research. This study developed asymmetric microcrystalline solidified pellets (AMSPs) with excellent stability, capable of precisely regulating the in vitro release of poorly soluble drugs. Based on the solubility-permeability theory, an effective method was proposed to predict the in vivo absorption behavior of these pellets. Using fenofibrate (FBT) as the model drug, a microcrystalline suspension was prepared via wet grinding to enhance the dissolution rate. The resulting suspension was then solidified onto the surface of blank pellets using an asymmetric layered loading strategy, yielding AMSPs that enhance the stability of the microcrystalline suspension while enabling controlled drug release. The surface structure of the steady-state crystals within the suspension was characterized as a dynamically equilibrated semi-solid phase using colorimetry and ¹H NMR spectroscopy. By varying drug loading density and mass ratios across different drug-loaded compartments, the release behaviors of different AMSP configurations were systematically analyzed to achieve precise in vitro controlled release. Further more, sodium taurocholate (STC) was selected as a representative compound to investigate the relationship between solubility and permeability, leading to the development of a predictive model for evaluating the effects of food and surfactants on drug absorption. Validated by single-pass jejunal perfusion and bioavailability studies, the model demonstrated strong potential to reduce the cost and experimental burden of in vitro and in vivo investigations while improving the prediction of oral bioavailability. In summary, this research provides valuable insights into the controlled release and oral absorption enhancement of poorly soluble drugs, contributing to their development in pharmaceutical sciences.