Preformulation Studies of the gamma-Cyclodextrin and Montelukast Inclusion Compound Prepared by Comilling
authors Barbosa, JS; Nolasco, MM; Ribeiro-Claro, P; Paz, FAA; Braga, SS
nationality International
journal JOURNAL OF PHARMACEUTICAL SCIENCES
author keywords mechanochemistry; coamorphisation; montelukast; molecular encapsulation; dissolution
keywords BETA-CYCLODEXTRIN; SODIUM; COMPLEXES; ASTHMA; DISSOLUTION; STABILITY; FTIR
abstract Montelukast (MLK), an oral antiasthmatic drug with growing use, requires special care in formulation and storage to avoid its degradation by action of light and water. This work investigates the increase in the stability of montelukast as the effect of molecular encapsulation with gamma-cyclodextrin (gamma-CD) by means of a solvent-free method, cogrinding. As a first step, a 1:1 preferred stoichiometry is established for this hostguest system using a combination of molecular modeling and the continuous variation method. The solid 1:1 inclusion compound, gamma-CD center dot MLK, is obtained by 2 comilling procedures. For comparison purposes, gamma-CD center dot MLK is also prepared by a classical codissolution procedure and isolated by freeze-drying. Products were characterized by powder X-ray diffraction, C-13{H-1} CP-MAS NMR, scanning electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry, which confirm inclusion, demonstrate the formation of amorphous products by comilling, and highlight the importance of the amorphous nature of the starting materials for the stability of the comilled final product. The dissolution profile of montelukast when released from the comilled products shows equivalent concentrations to those obtained with the same mass of the pure drug, with the extra advantage of keeping the solution stability (unaltered concentration) for longer periods. (C) 2019 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
publisher ELSEVIER SCIENCE INC
issn 0022-3549
isbn 1520-6017
year published 2019
volume 108
issue 5
beginning page 1837
ending page 1847
digital object identifier (doi) 10.1016/j.xphs.2018.11.047
web of science category Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy
subject category Pharmacology & Pharmacy; Chemistry
unique article identifier WOS:000477746900020
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journal analysis (jcr 2019):
journal impact factor 2.997
5 year journal impact factor 3.246
category normalized journal impact factor percentile 57.782
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