title: Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler.
abstract: BACKGROUND
  Dry powder inhalers (DPI) are generally formulated by mixing micronized drug particles with coarse lactose carrier particles to assist powder handling during the manufacturing and powder aerosol delivery during patient use.
  
  
  METHODS
  In the present study, surface modified lactose (SML) particles were produced using force control agents, and their in vitro performance on dry powder inhaler (DPI) formulation of Fluticasone propionate was studied. With a view to reduce surface passivation of high surface free energy sites on the most commonly used DPI carrier, α- lactose monohydrate, effects of various force control agents such as Pluronic F-68, Cremophor RH 40, glyceryl monostearate, polyethylene glycol 6000, magnesium stearate, and soya lecithin were studied.
  
  
  RESULTS
  DPI formulations prepared with SML showed improved flow properties, and atomic force microscopy (AFM) studies revealed decrease in surface roughness. The DSC and X-ray diffraction patterns of SML showed no change in the crystal structure and thermal behavior under the experimental conditions. The fine particle fraction (FPF) values of lactose modified with Pluronic F-68, Cremophor RH 40, glyceryl monostearate were improved, with increase in concentration up to 0.5%. Soya lecithin and PEG 6000 modified lactose showed decrease in FPF value with increase in concentration. Increase in FPF value was observed with increasing concentration of magnesium stearate. Two different DPI devices, Rotahaler(®) and Diskhaler(®), were compared to evaluate the performance of SML formulations. FPF value of all SML formulations were higher using both devices as compared to the same formulations prepared using untreated lactose. One month stability of SML formulations at 40°C/75% RH, in permeable polystyrene tubes did not reveal any significant changes in FPF values.
  
  
  CONCLUSIONS
  SML particles can help in reducing product development hindrances and improve inhalational properties of DPI.
authors.affiliation: 1 Department of Pharmaceutics, Bombay College of Pharmacy , Mumbai, India .
authors.forename: Deepak J
authors.initials: DJ
authors.lastname: Singh
authors.affiliation: 1 Department of Pharmaceutics, Bombay College of Pharmacy , Mumbai, India .
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Jain
authors.affiliation: 2 Board of Radiation and Isotope Technology and Medical Cyclotron Facility , Parel, Mumbai, India .
authors.forename: P S
authors.initials: PS
authors.lastname: Soni
authors.affiliation: 3 Department of Medicine, Bombay Veterinary College , Parel, Mumbai, India .
authors.forename: Samad
authors.initials: S
authors.lastname: Abdul
authors.affiliation: 1 Department of Pharmaceutics, Bombay College of Pharmacy , Mumbai, India .
authors.forename: Hegde
authors.initials: H
authors.lastname: Darshana
authors.affiliation: 3 Department of Medicine, Bombay Veterinary College , Parel, Mumbai, India .
authors.forename: Rajiv V
authors.initials: RV
authors.lastname: Gaikwad
authors.affiliation: 1 Department of Pharmaceutics, Bombay College of Pharmacy , Mumbai, India .
authors.forename: Mala D
authors.initials: MD
authors.lastname: Menon
mesh_terms: D000336:Aerosols; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004355:Drug Stability; D058995:Dry Powder Inhalers; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D000068298:Fluticasone / Q000008:administration & dosage* / Q000737:chemistry; D006813:Humidity; D007785:Lactose / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D033362:Powder Diffraction; D011208:Powders; D012212:Rheology; D013499:Surface Properties; D013696:Temperature; D013997:Time Factors
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D000068298:Fluticasone; D007785:Lactose
keywords: Fluticasone propionate; dry powder inhaler; force control agents; surface modified lactose