Production of Polymer-Based Nanoparticles

Abstract

Nanoparticles are submicron-sized particles, that is, particles with average size in the range of 1–1000 nm. This is a drug delivery vehicle, highly investigated by scientists to fulfill one or combination of following drug delivery goals like release rate modulation, protection from physiological environment, increase bioavailability. Nanonization is mostly targeted to increase dissolution rate of drug molecules, which are poorly soluble in water, that is, BCS class II and IV drugs. Nanoparticles can be broadly classified based on its chemical composition as drug nanocrystal-based nanosuspension or nanoparticles or natural polymer-based nanoparticles as lipid-based nanoparticles, protein- and peptide-based nanoparticles, polysaccharide-based nanoparticles, cyclodextrin-based macromolecular complexes, synthetic polymeric and copolymeric nanoparticles, PLGA, polyacrylates. These can also be nonpolymeric organic nanoparticles of carbon, metallic, silica based, etc. Such nanoparticles can be manufactured based on top-down methods/techniques involving reduction of particle size by nano-milling for production of nanocrystal-based polymer-stabilized drug nanoparticles formulation. The advantages and limitations and various processing considerations for nanosuspensions manufacturing involving agitator speed, media load, media type, media size, milling time are discussed in this chapter. Further, formulation considerations for nanocrystal nanosuspensions formation are discussed based on physicochemical properties of APIs, primary stabilizer properties, secondary stabilizer addition, stabilizer concentration. The approval status of different types of nanoparticles and commercially available formulations is also discussed in this chapter. Analytical characterization of nanosuspensions like particle size distribution, zeta potential, optical microscopy, solid-state characterization is also discussed in this chapter. Common issues of such top-down nanoparticle production are also discussed in this chapter like nanomilling, and when manufactured based on high-pressure homogenization (HPH), HPH in water (Dissocubes), homogenization in water-free media and water mixtures (Nanopure), HPH process variables, ultrasonication, laser fragmentation, etc. Further, bottom-up technology-based nanoparticle production is also discussed, which includes agglomeration-based nanoparticles and nanosphere, crystallization and precipitation methods, nanoprecipitation, polymer precipitation methods, crystallization of supersaturated solution, supercritical CO 2 to produce nanoparticles, evaporative methods that include spray-drying is a well-known evaporative method, spray freeze-drying, electrospraying. There are also combination methodologies and alternate approaches like emulsification methods, emulsification – solvent diffusion and evaporation method, double emulsification technique, emulsion coacervation, emulsification – reverse salting-out, poly-ionic complex and ionic gelation or nanogels, solvent injection method, “in situ” polymerization and interfacial polycondensation, self-assembling polyelectrolyte complex and complex coacervation, self-assembled micellar systems, microemulsion and nanoemulsion, complex coacervation and desolvation techniques, polymer coating and layer-by-layer method, dialysis techniques. Macromolecular complex for nanoparticles formation is also discussed based on dendrimeric complexes, solid dispersion (SD), carbon nanotubes. General considerations for scale-up and production of polymeric nanoparticles are also discussed, which include mixing considerations for conventional methods, simple mechanical stirring and probe sonication, and other alternate high-impact methods, microfluidic methods, etc. Scale-up challenges in nanomedicine manufacturing are also discussed in this chapter. Pilot-scale production of nanoparticles by two steps procedures involving emulsification–solvent diffusion and emulsification – reverse salting-out methods are described. Also one-step procedure-based nanoprecipitation of a polymer is described herein. Further, there are many nanoparticle purification and collection methods like evaporation under reduced pressure, centrifugation, ultracentrifugation methods, nano spray-drying, filtrations through mesh or filters, crossflow filtration, diaflitration, tangential flow filtration (TFF), purification by dialysis, gel filtration. Nanoparticle drying and storage techniques based on different process like freeze-drying of nanoparticles, spray-drying and different nanoparticle sterilization approaches are also described. Nanoparticle surface modification is done for targeting and stabilization is also described well in this chapter. There are many new commercial technologies of nanoparticle production which includes seamless scaling for nanomedicine development. Fit-For-Purpose Lipid Nanoparticle Portfolio, Advanced Technology for Advanced Genetic Medicines, Drug Discovery and Screening wi