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

Abstract

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.

Formulation Development and Evaluation of Montelukast Sodium Paper Tablets for Enhanced Drug Release

“…Currently, montelukast sodium is available in three different dosage formulations: chewable tablets, pills, and granules. 6 Nonetheless, despite their established efficacy, MS formulations have certain limits in their use, including the molecule's inadequate water solubility (100-1000 mg/mL), and its wavering stability to humidity, temperature, and light. 7 Hence, the current investigation aims to develop the paper tablets of a poorly soluble drug, montelukast sodium.…”