Inclusion complexes of atorvastatin calcium (ATV‐Ca) and rosuvastatin calcium (ROV‐Ca) drugs with α‐CD, β‐CD, γ‐CD, HP‐β‐CD, M‐β‐CD, and maltodextrin along with their characterizations through experimental and computational methods

Abstract

The aim of this research is a comparison of the efficiency of six commercially available cyclodextrins (CDs) to improve the solubility and oral bioavailability of atorvastatin calcium (ATV‐Ca) and rosuvastatin calcium (ROV‐Ca) drugs in aqueous media. Inclusion complexes of both drugs with non‐toxic α‐CD, β‐CD, γ‐CD, HP‐β‐CD, M‐β‐CD, and maltodextrin were prepared in a 1:1 stoichiometry via the kneading method. To reach the best CD, various experimental and computational analyses were performed including phase solubility, dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), hydrogen‐1 nuclear magnetic resonance (1HNMR), carbon‐13 nuclear magnetic resonance (13CNMR), and molecular docking calculations. The M‐β‐CD turned out to be the best substrate for the micro‐encapsulation of both drugs. Also, ATV showed a higher tendency than ROV to form inclusion complexes with CDs. Molecular docking studies showed that HP–β–CD and M‐β‐CD are the most suitable substrates for the formation of inclusion complexes, respectively. Our research showed that the β‐CD is not necessarily the most efficient substrate for increasing solubility based on previous reports in the literature; meanwhile, the other employed substrates in this study can show acceptable performances in this regard. According to our results, M‐β‐CD is the best substrate for the micro‐encapsulation of both drugs, which increases their solubility in water.

Revealing a notable interaction in the binding of type II statins to HMG‐CoA reductase: Stacked cation–π interaction

“…Therapeutically, it is significant to research and develop new drugs 5–7 and devices 8,9 so as to decrease the level of blood cholesterol. Statins 10 are a well‐known therapy for lowering LDL cholesterol. They inhibit 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase by holding an HMG‐like moiety (mevalonate structure) as their core structure.…”