K. Sirkar, D. Chen, D. Singh, C. Jin, R. Pfeffer
New Jersey Institute of Technology,
Keywords: continuous polymer coating, drug crystals, submicron particles and nanoparticles, hollow fiber membranes, cooling crystallization and anti-solvent crystallization
Summary: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. Such coatings are also integral to controlled drug delivery processes. Conventional approaches to fabrication of such coatings are quite cumbersome and require very demanding operating conditions e.g., very high pressure in supercritical fluid-based processes. Further these approaches generally employ batch techniques. Scale-up is problematic. We have adapted the technique of solid hollow fiber cooling crystallization (SHFCC) as well as the technique of porous hollow fiber membrane-based anti-solvent crystallization (PHFAC) to continuously produce polymer-coated drug crystals and particles. These two hollow fiber membrane-based techniques are easily scalable. Both submicron particles and nanoparticles especially of silica 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. (This technique has been additionally used to continuously coat submicron and nanoparticles of silica.) A similar result was also achieved by the SHFCC process. 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 scanning electron microscopy (SEM), scanning transmission electron microscopy (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 analysed after vacuum drying using SEM, STEM, energy dispersive spectrometry, LDS and TGA. Scale up has been demonstrated using hollow fiber membrane modules of different dimensions containing different numbers of hollow fiber membranes. Extended duration runs have been conducted for two hours to demonstrate no variation in product quality using the SHFCC technique. One US patent has already been issued and another patent application is under review.