ABSTRACT
Drug nanoparticles prepared in a liquid medium are commonly freeze-dried for the preparation of an oral dosage in solid dosage form. The freezing rate is known to be a critical parameter for redispersible nanoformulations. However, there has been controversy as to whether a fast or slow freezing rate prevents irreversible aggregation. A systematic investigation is presented herein regarding the effect of both the molecular weight of the cryoprotectant and the freezing rate in order to elucidate the mechanism underlying irreversible aggregation. It was found that irreversible aggregation occurred during drying rather than freezing, although a proper freezing rate is critical. A more homogeneous distribution of the cryoprotectant and drug nanoparticles led to more redispersible powders. Thus, keeping the local concentration distribution of the nanoparticles and cryoprotectant fixed during the freezing step plays a critical role in how the freezing rate affects the redispersibility. The kinetic approach of excluding the tendency of ice crystal growth permitted an explanation of the controversial results. This study will facilitate an in-depth understanding of the aggregation process of nanoparticles or proteins during freeze-drying.
Subject(s)
Drug Compounding/methods , Nanoparticles/chemistry , Crystallization , Freeze Drying , Microscopy, Electron, Scanning , Nanoparticles/ultrastructure , Naproxen/chemistry , Particle Size , Polyethylene Glycols/chemistry , Spectroscopy, Fourier Transform Infrared , SuspensionsABSTRACT
Recently, researchers have tried to produce non-spherical and anisotropic particles to be used in the next generation of multi-functional materials. Of key interest is the red blood cell-like particle. The torus structure was produced under the relatively fast consolidation of monodisperse droplets, and its parameters were found to be tunable by temperature as well as solvent type and concentration. The observation of consolidation demonstrated that the polymers were accumulated and solidified in the torus structure, naturally, whereas there was the critical droplet size to induce the asymmetry diffusivities. The torus structures could be simply tuned by the flow rate and concentration. The coaxial nozzle system produced the core/shell torus particles. These results state that the consolidation mechanism can hold important clues to enhance the range of tuning capabilities.