(659f) Continuous Production of Polymer Coated Drug Crystals, Particles and Nanoparticles

Polymeric coating can provide protection for fragile drugs from hydrolysis and degradation. With an appropriate polymer coating, nanoparticles are known to traverse the physiological human mucous barrier. Conventional approaches to such fabrication are quite cumbersome and often employ batch techniques. We have adapted the technique of solid hollow fiber cooling crystallization (SHFCC) as well as the technique of porous hollow fiber based anti-solvent crystallization (PHFAC) to continuously produce polymer-coated drug crystals and particles. Both submicron particles and nanoparticles have been coated. We have also continuously synthesized polymer-coated drug crystals by anti-solvent crystallization from a solution of the drug and the polymer. The synthesized polymer-coated drug crystals involve crystals of the drug Griseofulvin (GF) coated by a thin layer of the polymer Eudragit RL100. In the case of particles, submicron (550 nm) and nano-sized (12 nm) silica particles acted as the host particles; Eudragit RL 100 and poly (lactide-co-glycolide) were the coating polymers. For the polymer-coated drug crystals, the surface morphology, particle size distribution, and the polymer coating thickness were characterized by SEM, STEM, laser diffraction spectroscopy (LDS) and thermogravimetric analysis (TGA). To study the properties of the coated drug crystals, x-ray diffraction (XRD), Raman spectroscopy, and dissolution test were implemented. Coated silica particles were analyzed after vacuum drying using SEM, STEM, energy dispersive spectrometry, LDS and TGA. Scaleup has been demonstrated using hollow fiber modules of different dimensions. Extended duration runs have been conducted for two hours to demonstrate no variation in product quality.