Effect of albumin on physical characteristics of drug particles produced by supercritical fluid technology

In this study, two drugs, terbutaline sulphate (TS) and ipratropium bromide (IB), were micronized by means of a CO2-based aerosol solvent extraction system (ASES). TS and IB particles with albumin as additive were also precipitated in order to improve the powder flow behavior in an accelerating air flow. Albumin is considered an inactive ingredient for FDA-approved drugs and is endogenous to the lung. The addition of albumin affected the particle morphology resulting in improved aerosolization properties. In the present study, ASES experiments were conducted using a mixed solvent of ethanol/dimethylformamide (EtOH/DMF) for the micronization of TS and pure DMF was used as solvent for IB. For the respirable TS, optimum processing conditions were at about 100 bar and 50 °C. For the IB particles, the conditions were at 200 bar and 40 °C. The aerosol characteristics of all precipitated drug particles in this work were analyzed by comparing the particle size distribution (PSD) and the associated mass median aerodynamic diameter (MMAD) measured by scanning electron microscopy (SEM) to those obtained from Aerodynamic Particle Sizer (APS) and from the Micro-orifice Uniform Deposit Impactor (MOUDI). The results indicate that the TS and IB particles with albumin are less cohesive and less agglomerated in air flow, thus leading to more effective and consistent lung deposition.

Aerosol delivery efficiency was improved by modifying the shape of ipratropium bromide and terbutaline sulphate drug particles with the addition of albumin as an excipient. The drug particles were produced using a supercritical antisolvent process. SEM, APS and MOUDI analyses show that the addition of albumin significantly affected particle morphology and interparticle interactions producing particles which are more regular in shape and less agglomerated, leading to more effective and consistent lung deposition.Figure optionsDownload as PowerPoint slide