title: Towards crystal engineering via simulated pulmonary surfactant monolayers to optimise inhaled drug delivery.
abstract: OBJECTIVE
  To generate theophylline monohydrate crystals underneath Langmuir monolayers composed of material expressed at the alveolar air-liquid interface. Such monolayers can act as nucleation sites to direct crystallisation. The approach offers a novel route to rationally engineer therapeutic crystals and thereby optimise inhaled drug delivery.
  
  
  METHODS
  Langmuir monolayers consisting of either dipalmitoylphosphatidylcholine (DPPC) or a surfactant mix reflecting pulmonary surfactant were supported on an aqueous theophylline (5.7 mg/ml) subphase. The monolayers were compressed to surface pressures reflecting inhalation and exhalation (i.e. 5 mNm(-1) or 55 mNm(-1)) with a period of 16 h to allow crystallisation. Analysis involved scanning electron microscopy (SEM), atomic force microscopy (AFM) and powder X-ray diffraction (PXRD).
  
  
  RESULTS
  Condensed isotherms were acquired, which signified surfactant-theophylline interaction. Theophylline monohydrate crystals were obtained and exhibited needle-like morphology. SEM and AFM data highlighted regions of roughened growth along with smooth, stepwise growth on the same crystal face. The surfactant monolayers appeared to influence crystal morphology over time.
  
  
  CONCLUSIONS
  The data indicate a favourable interaction between each species. The principal mechanism of interaction is thought to be an ion-dipole association. This approach may be applied to generate material with improved complementarity with pulmonary surfactant thus enhancing the interaction between inhaled drug particles and internal lung surfaces.
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: Linda
authors: L
authors: Seton
authors: Nicola
authors: N
authors: Tiernan
authors: Mark F
authors: MF
authors: Murphy
authors: Paul
authors: P
authors: Gibbons
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000737:chemistry; D003460:Crystallization; D016503:Drug Delivery Systems; D019308:Palmitic Acid / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D013806:Theophylline / Q000737:chemistry*
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; D013806:Theophylline