title: The crystal engineering of salbutamol sulphate via simulated pulmonary surfactant monolayers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: The School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK. m.davies1@ljmu.ac.uk
authors: Michael J
authors: MJ
authors: Davies
authors: Thomas D
authors: TD
authors: Kerry
authors: Linda
authors: L
authors: Seton
authors: Mark F
authors: MF
authors: Murphy
authors: Paul
authors: P
authors: Gibbons
authors: Jiyi
authors: J
authors: Khoo
authors: Majid
authors: M
authors: Naderi
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000420:Albuterol / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000737:chemistry*; D002849:Chromatography, Gas; D003460:Crystallization; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D019308:Palmitic Acid / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical
chemical_list: D001993:Bronchodilator Agents; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; D019308:Palmitic Acid; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D000420:Albuterol