Preventing crystal agglomeration of pharmaceutical crystals using temperature cycling and a novel membrane crystallization procedure for seed crystal generation

In this work, a novel membrane crystallization system was used to cr ystallize micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition. Membrane crystallization seeds were compared with seeds produced by conventional antisolvent addition and polymorphic transformation of a fine powdered sample of piroxicam form I in water. The membrane crystallization process allowed for a consistent production of pure monohydrate crystals with narrow size distribution and without significant agglomeration. The seeds were grown in 350 g of 20:80 w/w acetone-water mixture. Different seeding loads were tested and temperature cycling was applied in order to avoid agglomeration of the growing crystals during the process. Focused beam reflectance measurement (FBRM); and particle vision and measurement (PVM) were used to monitor crystal growth; nucleation and agglomeration during the seeded experiments. Furthermore; Raman spectroscopy was used to monitor solute concentration and estimate the overall yield of the process. Membrane crystallization was proved to be the most convenient and consistent method to produce seeds of highly agglomerating compounds; which can be grown via cooling crystallization and temperature cycling

Double emulsion production in glass capillary microfluidic device: Parametric investigation of droplet generation behaviour

A three-phase axisymmetric numerical model based on Volume of Fluid–Continuum Surface Force (VOF–CSF) model was developed to perform parametric analysis of compound droplet production in three-phase glass capillary devices that combine co-flow and countercurrent flow focusing. The model predicted successfully generation of core–shell and multi-cored double emulsion droplets in dripping and jetting (narrowing and widening) regime and was used to investigate the effects of phase flow rates, fluid properties, and geometry on the size, morphology, and production rate of droplets. As the outer fluid flow rate increased, the size of compound droplets was reduced until a dripping-to-jetting transition occurred. By increasing the middle fluid flow rate, the size of compound droplets increased, which led to a widening jetting regime. The jetting was supressed by increasing the orifice size in the collection capillary or increasing the interfacial tension at the outer interface up to 0.06 N/m. The experimental and simulation results can be used to encapsulate CO2 solvents within gas-permeable microcapsules

Dynamics of double emulsion break-up in three phase glass capillary microfluidic devices

Pinch-off of a compound jet in 3D glass capillary microfluidic device, which combines co-flowing and countercurrent flow focusing geometries, was investigated using an incompressible three-phase axisymmetric Volume of Fluid–Continuum Surface Force (VOF–CSF) numerical model. The model showed good agreement with the experimental drop generation and was capable of predicting formation of core/shell droplets in dripping, narrowing jetting and widening jetting regimes. In dripping and widening jetting regimes, the presence of a vortex flow around the upstream end of the necking thread facilitates the jet break-up. No vortex flow was observed in narrowing jetting regime and pinch-off occurred due to higher velocity at the downstream end of the coaxial thread compared to that at the upstream end. In all regimes, the inner jet ruptured before the outer jet, preventing a leakage of the inner drop into the outer fluid. The necking region moves at the maximum speed in the narrowing jetting regime, due to the highest level of shear at the outer surface of the thread. However, in widening jetting regime, the neck travels the longest distance downstream before it breaks

Highly Porous Magnetic Janus Microparticles with Asymmetric Surface Topology.

Monodispersed magnetic Janus particles composed of a porous polystyrene portion and a nonporous poly(vinyl acetate) portion with embedded oleic acid-coated magnetic nanoparticles were generated using microfluidic emulsification followed by two distinct phase separation events triggered by solvent evaporation. The template droplets were composed of 2 wt % polystyrene, 2 wt % poly(vinyl acetate), and 0.5-2 wt % n-heptane-based magnetic fluid dissolved in dichloromethane (DCM). The porosity of polystyrene compartments was the result of phase separation between a nonvolatile nonsolvent (n-heptane) and a volatile solvent (DCM) within polystyrene-rich phase. The focused ion beam cross-sectioning and scanning electron microscopy (SEM) imaging revealed high surface porosity of polystyrene compartments with negligible porosity of poly(vinyl acetate) parts, which can be exploited to increase the wettability contrast between the two polymers and enhance bubble generation in bubble-driven micromotors. The porosity of the polystyrene portion was controlled by varying the fraction of n-heptane in the dispersed phase. The particle composition was confirmed by scanning electron microscopy-energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The fabricated particles were successfully magnetized when subjected to an external magnetic field, which led to their aggregation into regular 2D assemblies. The particle clusters composed of two to four individual particles could be rotated with a rotating magnetic field. Microfluidic generation of highly porous Janus particles with compositional, topological, and magnetic asymmetry provides a cost-effective, easy-to-implement yet highly robust and versatile strategy for the manufacturing of multifunctional smart particles