Investigations into the formulation of metered dose inhalers of salmeterol xinafoate and fluticasone propionate microcrystals.
OBJECTIVE
To investigate the aerosolization and behaviour of microparticles of salmeterol xinafoate (SX) and fluticasone propionate (FP) suspended in hydrofluoroalkane (HFA) propellant.


METHODS
Microcrystals of SX and FP were produced from poly(ethylene glycol) by antisolvent crystallization. The suspension behaviour and aerosolization of the microcrystals when formulated as metered dose inhalers (MDIs) in HFA 134a propellant was compared with that of microparticles produced by micronization (mSX and mFP) using a glass twin stage impinger and by laser light diffraction using a pressurized cell.


RESULTS
FP microparticles underwent non-reversible aggregation in suspension as seen by a doubling in the volume median diameter compared to the raw material. The degree of aggregation of SX particles in suspension was found to decrease as the particle size of the original particles increased. However, because the SX aggregate size was lowest for the particles with the smallest initial size (mSX), the highest fine particle fraction (FPF) of SX was obtained from a suspension of mSX. The FPFs following aerosolization of FP suspensions were similar although the FPF was lowest for particles with the largest original size.


CONCLUSIONS
The size of the aggregates in the HFA suspensions was found to correlate directly with the FPFs determined by impaction.
King's College London, Drug Delivery Research Group, Pharmaceutical Science Division, 150 Stamford Street, London, SE1 9NH, UK.
Darragh
D
Murnane
Gary P
GP
Martin
Christopher
C
Marriott
D000280:Administration, Inhalation; D000335:Aerosol Propellants; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D036501:Metered Dose Inhalers; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011312:Pressure; D015203:Reproducibility of Results; D000068299:Salmeterol Xinafoate; D013678:Technology, Pharmaceutical / Q000379:methods; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000336:Aerosols; D000420:Albuterol; D000730:Androstadienes; D001993:Bronchodilator Agents; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D011092:Polyethylene Glycols; D000068299:Salmeterol Xinafoate; C094049:apaflurane; D005466:Fluorocarbons