title: Lactose surface modification by decantation: are drug-fine lactose ratios the key to better dispersion of salmeterol xinafoate from lactose-interactive mixtures?
abstract: OBJECTIVE
  The role of fine lactose in the dispersion of salmeterol xinafoate (SX) from lactose mixtures was studied by modifying the fine lactose concentration on the surface of the lactose carriers using wet decantation.
  
  
  METHODS
  Fine lactose was removed from lactose carriers by wet decantation using ethanol saturated with lactose. Particle sizing was achieved by laser diffraction. Fine particle fractions (FPFs) were determined by Twin Stage Impinger using a 2.5% SX mixture, and SX was analyzed by a validated high-performance liquid chromatography method. Adhesion forces between probes of SX and silica and the lactose surfaces were determined by atomic force microscopy.
  
  
  RESULTS
  FPFs of SX were related to fine lactose concentration in the mixture for inhalation grade lactose samples. Reductions in FPF (2-tp 4-fold) of Aeroflo 95 and 65 were observed after removing fine lactose by wet decantation; FPFs reverted to original values after addition of micronized lactose to decanted mixtures. FPFs of SX of sieved and decanted fractions of Aeroflo carriers were significantly different (p < 0.001). The relationship between FPF and fine lactose concentration was linear. Decanted lactose demonstrated surface modification through increased SX-lactose adhesion forces; however, any surface modification other than removal of fine lactose only slightly influenced FPF.
  
  
  CONCLUSIONS
  Fine lactose played a key and dominating role in controlling FPF. SX to fine lactose ratios influenced dispersion of SX with maximum dispersion occurring as the ratio approached unity.
authors.affiliation: Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville Victoria 3052, Australia.
authors.forename: Nazrul
authors.initials: N
authors.lastname: Islam
authors.forename: Peter
authors.initials: P
authors.lastname: Stewart
authors.forename: Ian
authors.initials: I
authors.lastname: Larson
authors.forename: Patrick
authors.initials: P
authors.lastname: Hartley
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D010316:Particle Size; D000068299:Salmeterol Xinafoate
chemical_list: D004337:Drug Carriers; D000068299:Salmeterol Xinafoate; D007785:Lactose; D000420:Albuterol