Inclusion of Montelukast in y-Cyclodextrin: Presenting a Mechanochemical Route to Improve Drug Stability and Solubility

Montelukast sodium (MLK) is a worldwide antiasthmatic drug. Commercial formulations still have some issues with solubility and instability to light and humidity. To overcome them, the present work reports inclusion compounds of MLK and γ-cyclodextrin (γ-CD). As a molecular capsule, CDs have the ability to protect the inclusion guest from degradation, enhance its solubility and alter the pharmacokinetic parameters. MLKγ-CD inclusion compounds were prepared by mechanochemistry. Without using any solvent, γ-CD was pre-milled and then co-milled with an equimolar quantity of MLK in a ball mill at 600 cycles·min−1. After 120 min of milling, the formation of MLK·γ-CD inclusion compounds was confirmed by powder X-ray diffraction and scanning electron microscopy. Additional studies, performed under pharmacopeia guidelines, showed that the prepared MLKγ-CD inclusion compounds can indeed increase the dissolution of MLK when in ultrapure water or simulated intestinal fluid (without pancreatin). This way, the MLKγ-CD inclusion compounds that are presented in this work are a promising solution for improving the therapeutic effectiveness of MLK.