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Inclusion of Montelukast in y-Cyclodextrin: Presenting a Mechanochemical Route to Improve Drug Stability and Solubility †
* 1, 2 , 1 , 2 , 1
1  Department of Chemistry, LAQV-REQUIMTE, University of Aveiro, 3810-193 Aveiro, Portugal
2  Department of Chemistry, CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal

Abstract:

Montelukast sodium (MLK) is a worldwide anti asthmatic 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 g-cyclodextrin (g-CD). As a molecular capsule, CDs have the ability to protect the inclusion guest from degradation, enhance its solubility and alter the pharmacokinetic parameters. MLK×g-CD inclusion compounds were prepared by mechanochemistry. Without using any solvent, g-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·g-CD inclusion compounds was confirmed by powder X Ray diffraction and scanning electron microscopy. Additional studies, performed under Pharmacopeia guidelines, showed that the prepared MLK×g-CD inclusion compounds can indeed increase the dissolution of MLK drug when in ultra-pure water or simulated intestinal fluid (without pancreatin). This way, the MLK×g-CD inclusion compounds that are presented in this work are a promising solution for improving the therapeutic effectiveness of MLK drug.

Keywords: Montelukast; Cyclodextrins; Mechanochemistry; Inclusion Compounds; Drug Solubility
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