International Journal of Pharmaceutics 2013-03-25

The crystal engineering of salbutamol sulphate via simulated pulmonary surfactant monolayers.

Michael J Davies, Thomas D Kerry, Linda Seton, Mark F Murphy, Paul Gibbons, Jiyi Khoo, Majid Naderi

Index: Int. J. Pharm. 446(1-2) , 34-45, (2013)

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Abstract

This study aims to crystallise salbutamol sulphate beneath simulated pulmonary surfactant monolayers. Such ensembles serve as heterogeneous nucleating sites to direct crystallisation. This contribution builds upon previous work to confirm the suitability of Langmuir monolayers in supporting the rational generation of respirable therapeutic material.Langmuir monolayers (i.e. DPPC or a 'mixed' system) were supported on a subphase containing the extremely water soluble model drug (2.5 g/ml) and compressed to 5 mN m(-1) or 35 mN m(-1) whilst experiencing a temperature reduction and positioned within a humid environment. Control samples were produced via batch crystallisation. Analysis involved scanning electron microscopy (SEM), atomic force microscopy (AFM), powder X-ray diffraction (PXRD) and inverse gas chromatography (IGC).Expanded Langmuir isotherms confirmed drug-surfactant interaction; crystal growth was inhibited at high surface pressure. Resultant crystals exhibited a range of morphologies, dependent upon the crystallisation route. AFM analysis highlighted nanoscale surface undulations. IGC data confirmed sample surface energy profiles were variable and influenced by crystallisation route.Principal modes of drug-surfactant interaction are proposed as hydrogen bond and ion-dipole associations. A range of pharmaceutical approaches have been applied to understand drug-surfactant complementarity. The results strengthen the argument for the use of Langmuir monolayers in drug particle engineering.Copyright © 2013 Elsevier B.V. All rights reserved.