Development of antihyperlipidemic drug loaded β-CD-based microparticulate carrier systems: tuning and optimization

Abstract

ABSTRACT Our study focused on developing and optimizing β-CD-based microparticulate carrier systems to enhance lovastatin’s solubility and systemic availability (LST). Specifically, we designed solid dispersions, inclusion complexes, and hydrogel microparticles as carrier systems. Fourier-transform infrared spectroscopy (FTIR) studies were conducted to ensure drug–polymer interactions and ingredient compatibility. Additionally, we investigated the physical state, thermal stability, topology, internal morphology, and particle size using techniques such as powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta size, and zeta potential. Our results confirmed the formation of compatible and thermally stable networks within an acceptable particle size range. The entrapment efficiency and product yield fell within 83.50–88.50% and 87–90.50%, respectively. Notably, all developed formulations exhibited a significant increase in solubility at pH 6.8 compared to LST commercial Tablets, as indicated by the regression coefficient (R2) for the release of LST following first-order kinetics. We compared LST commercial tablets with our optimized formulations (SD3 and HA3) for pharmacokinetic evaluation. SD3 demonstrated a Cmax of 63.64 µg/ml, an AUC o-t of 555.79 µg/ml.h, and a half-life (t1/2) of 7.3 h. In contrast, HA3 exhibited superior pharmacokinetic parameters with a Cmax of 93.543 µg/ml, an AUC o-t of 1154.35 µg/ml.h, and a t1/2 of 10.33 h. These results indicate the efficient release of LST from the developed carrier systems, supported by increased Cmax and lower tmax values. Furthermore, biochemical and histopathological studies on our optimized formulations confirmed their biocompatibility. Our findings demonstrate our developed β-CD-based microparticulate carrier systems’ effectiveness in enhancing lovastatin’s solubility, systemic availability, and biocompatibility.