Physicochemical characteristics of the complexes of simvastatin and Atorvastatin calcium (cas 134523-03-8) with hydroxypropyl-β-cyclodextrin produced by mechanochemical activation
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Add time:08/06/2019 Source:sciencedirect.com
In the present work, inclusion complexes of simvastatin (SIM), Atorvastatin calcium (cas 134523-03-8) (ATV) with hydroxypropyl-β-cyclodextrin (HP-β-CD) have been prepared using mechanochemistry technique to improve solubility of the two drugs and enhance their oral bioavailability. The interactions of the drugs with HP-β-CD were investigated by DSC, XRD, SEM and 1HNMR. The stoichiometry of the inclusion complexes was determined by phase-solubility analysis. Furthermore, molecular docking study showed that the whole SIM molecule was completely embedded into the HP-β-CD cavity, and the part of the ATV molecule was most likely inserted into the cavity of HP-β-CD. The parallel artificial membrane permeability assay (PAMPA) revealed a strong increasing of SIM permeability in the presence of HP-β-CD in comparison with pure SIM used as a control. The pharmacokinetic study in vivo revealed that the bioavailability of mechanochemical treatment samples was significantly increased compared with that of the net drugs. On the other hand, the rapid storage assay (+40 °C for 3 months) showed that the chemical stability of inclusion complexes was higher than pure drugs. Therefore, the mechanochemically synthesized complexes of SIM/HP-β-CD and ATV/HP-β-CD could be a promising approach for the oral delivery of SIM and ATV for enhanced bioavailability.
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