Low-temperature aerosol flow reactor method for preparation of surface stabilized pharmaceutical nanocarriers

Nanoparticles can be used to improve the delivery of many drugs, especially peptides and proteins. Although several methods are available for polymeric nanoparticle preparation, there are few single-stage processes that produce dry, solid nanoparticles that can be easily re-dispersed in pharmaceutical vehicles. The aerosol flow reactor method is a single-stage process that has been used for the preparation of multicomponent, coated nanoparticles under uniform temperature and gas flow field. However, it is traditionally used with high synthesis temperatures. In the present study, the aerosol flow reactor method was further optimized for processing and surface stabilization of pharmaceutical nanoparticles containing temperature sensitive biomolecules. In the developed method, drug-loaded carrier nanoparticles consisting of a biodegradable polymer (Eudragit L100) and a drug (phenylephrine hydrochloride) were first produced by aerosol droplet drying and subsequently coated in the gas phase. The carrier particles were coated with l-leucine in order to inhibit agglomeration of the nanoparticles in solutions before administration. In the coating process, a side stream of l-leucine vapor was directed into the main aerosol flow containing the drug-loaded carriers. The mixing with the main flow at ambient temperature induced a supersaturation of l-leucine vapor and condensation on the carrier particles. The results demonstrate that solid, hydrodynamically stable drug-loaded polymeric nanoparticles can be produced with a thin l-leucine coating. The low process temperature enables the surface engineering of particles loaded with temperature sensitive drugs or bioactive materials to be utilized for drug delivery purposes.