Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Biochemistry

Background:

• Simvastatin (SIM) exhibits poor solubility and oral bioavailability, limiting its therapeutic efficacy.
• Developing advanced drug delivery systems is crucial for improving the performance of hydrophobic drugs like SIM.
• Mechanochemical techniques offer a solvent-free approach for creating novel drug formulations.

Purpose of the Study:

• To prepare and characterize simvastatin (SIM) complexes with arabinogalactan (AG) and disodium glycyrrhizinate (Na2GA) using mechanochemistry.
• To evaluate the impact of these complexes on SIM's solubility, permeability, stability, and oral bioavailability.
• To assess the potential of these novel SIM formulations for hypercholesterolemia management.

Main Methods:

• Complexation of SIM with AG or Na2GA via mechanochemical technique.
• Characterization using FTIR, DSC, XRD, SEM, UV/Vis, and NMR spectroscopy.
• Assessment of permeability using PAMPA assay, chemical stability via storage assay, and pharmacokinetic evaluation in vivo.

Main Results:

• Mechanochemically prepared SIM/AG and SIM/Na2GA complexes demonstrated improved solubility and oral bioavailability.
• SIM/Na2GA complexes exhibited enhanced chemical stability compared to pure SIM.
• In vivo pharmacokinetic studies confirmed a significant increase in SIM bioavailability.
• The SIM/AG inclusion complex showed superior efficacy in reducing total cholesterol levels.

Conclusions:

• Mechanochemically synthesized SIM/AG and SIM/Na2GA complexes represent promising novel formulations for improving SIM's therapeutic profile.
• These advanced formulations hold potential for effective management of hypercholesterolemia.
• The study highlights the utility of mechanochemistry in developing enhanced drug delivery systems.