Preparation And Evaluation Of Spray-dried Formulations For Pulmonary Drug Delivery

Objective: This study is aimed to prepare dry powder formulations with enhanceddispersibility and sustained drug release for pulmonary drug delivery.Contents:(1) The methods were established for the evaluation of DPI formulations,including the determination of the drug amount, the observation and analysis of powderphysicochemical properties, and the examination of in-vitro lung deposition and drugdissolution.(2) A series of DPI formulations were prepared through using different excipientsto modify the spray-drying solutions, with the aim to improve the dispersibility and lungdeposition of spray-dried powders, and also to sustain the drug release for elongate treatmentin the lungs.(3) The pullulan was used as excipient to modify the spray-dried powders. Thisnew dry powders were subsequently investigated in the in-vitro lung deposition and in-vitrodrug dissolution.Results:(1) The HPLC determination method of SS was stable and reliable; all the othermethods were easy to operate and able to investigate properties of sustained drug releaseprepared in all respects.(2) Spray drying was a feasible approach to prepare powders withcontrollable parameters and the optimized method was: concentration of feed solutions0.6-1.5%(w/v), inlet temperature150-170oC, pump rate300-420mL·h-1, spray flow rate600-700L·h-1, aspirator efficiency100%, outlet temperature85±3oC and the nozzle holediameter was1.5mm. Particles size of spray-dried powders was mostly distributed from1to10μm and the aerosolisation performance of generated DPI formulations were good, withthe fine particles fraction was45-65%and emitted dose was over90%.(3) The use ofleucine in the spray-drying solution can dramatically decreased the particle size and improveflowability property of spray-dried pullulan particles. The addition of acetone or ethanol inthe spray-drying solution can dramatically decrease the density of spray-dried. Moreimportantly the addition of NH4HCO3in the spray-drying solution can make porous particlesand obtain ultra-light spray-dried powders. These modified dry powders showed improveddispersibility and lung deposition. All pullutan-modified dry powder formulationsdemonstrated a sustained drug release in the in-vitro dissolution test.(4) The lactose,beta-cyclodextrin or starch-modified spray-dried powders showed an immediate release.However, NaCMC-SS or chitosan-SS powders showed a significant increase of drugdeposition in the lower respiratory tract and sustained release properties. Above all, pullulan-modified spray-dried powders presented a successful sustained drug release systemwith superior fine particle fraction.Conclusion: The preparation and evaluation methods of salbutamol sulphate sustainedrelease dry powder formulation for pulmonary delivery were successfully established. Aseries of dry powder formulations were prepared with improved aerosolisation performance,and short-or long-drug release profiles, potentially offering a great option to meet the clinicalrequirements for the treatment of lung disease.