Engineered mannitol as an alternative carrier to enhance deep lung penetration of salbutamol sulphate from dry powder inhaler.
In this research mannitol particles were prepared by recrystallisation using non-solvent precipitation technique to investigate the effect of engineered carrier particles on their physicochemical properties and the in vitro deposition profiles of a model drug (salbutamol sulphate (SS)) from a dry powder inhaler (DPI). To this end, mannitol aqueous solution (15%, w/v) was added to different ratios of ethanol:water (100:0, 95:5, 90:10 and 85:15) to obtain mannitol particles. These crystallised mannitol particles were analysed in terms of micromeritic properties, morphology, DSC, FT-IR, and in vitro fine particle fraction (FPF) and emitted dose (ED) of SS. The results showed that the elongation ratio of all the recrystallised mannitol batches was higher than the original material giving them a needle-shaped morphology. Salbutamol sulphate deposition profiles from DPI formulation containing recrystallised needle-shaped mannitol showed enhanced performance and better delivery to the lower MSLI stages. The FPF increased from 15.4+/-1.1 to 45.8+/-0.7% when the commercial mannitol was replaced by mannitol crystallised from ethanol:water (90:10). This improvement could be due to the presence of elongated mannitol crystals in formulation blends. Solid state characterisation of engineered mannitol showed that the commercial mannitol was beta-form, mannitol recrystallised from ethanol:water (85:15) was alpha-form and that samples recrystallised in presence of pure ethanol or other ratios of ethanol:water (95:5 and 90:10) were the mixtures of alpha-, beta- and delta-forms. Multi-solvent recrystallisation technique was proved to have potential to produce mannitol crystals suitable for enhanced aerosolisation efficiency. Comparing different crystallised mannitol formulations showed that the final form (the type of polymorph) of the crystallised mannitol does not have a substantial effect on salbutamol sulphate aerosolisation performance.
Chemistry and Drug Delivery Group, Universities of Kent and Greenwich, Kent ME4 4TB, UK.
Waseem
W
Kaialy
Mohammed N
MN
Momin
Martyn D
MD
Ticehurst
John
J
Murphy
Ali
A
Nokhodchi
D000420:Albuterol / Q000008:administration & dosage* / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D008168:Lung / Q000187:drug effects*; D008353:Mannitol / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties / Q000187:drug effects; D014961:X-Ray Diffraction
D004337:Drug Carriers; D011208:Powders; D008353:Mannitol; D000420:Albuterol