Marijana M. Dragosavac

Production of Porous Silica Microparticles by Membrane Emulsification

A method for the production of near-monodispersed spherical silica particles with controllable porosity based on the formation of uniform emulsion droplets using membrane emulsification is described. A hydrophobic metal membrane with a 15 μm pore size and 200 μm pore spacing was used to produce near-monodispersed droplets, with a mean size that could be controlled between 65 and 240 μm containing acidified sodium silicate solution (with 4 and 6 wt % SiO(2)) in kerosene. After drying and shrinking, the final silica particles had a mean size in the range between 30 and 70 μm. The coefficient of variation for both the droplets and the particles did not exceed 35%. The most uniform particles had a mean diameter of 40 μm and coefficient of variation of 17%. By altering the pH of the sodium silicate solution and aging the gel particles in water or acetone, the internal structure of the silica particles was successfully modified, and both micro- and mesoporous near-monodispersed spherical particles were produced with an average internal pore size between 1 and 6 nm and an average surface area between 360 and 750 m(2) g(-1). A material balance and particle size analysis provided identical values for the internal voidage of the particles, when compared to the voidage as determined by BET analysis.

Azimuthally Oscillating Membrane Emulsification for Controlled Droplet Production

A novel membrane emulsification (ME) system is reported consisting of a tubular metal membrane, periodically azimuthally (tangentially) oscillated with frequencies up to 50 Hz and 7 mm displacement in a gently cross flowing continuous phase. A computational fluid dynamics (CFD) analysis showed consistent axial shear at the membrane surface, which became negligible at distances from the membrane surface greater than 0.5 mm. For comparison, CFD analysis of a fully rotating ME system showed local vortices in the continuous phase leading to a variable shear along the axis of the membrane. Using an azimuthally oscillating membrane, oil-in-water emulsions were experimentally produced with a median diameter of 20–120 μm, and a coefficient of variation of droplet size of 8%. The drop size was correlated with shear stress at the membrane surface using a force balance. In a single pass of continuous phase, it was possible to achieve high dispersed phase concentrations of 40% v/v.

Polycaprolactone multicore-matrix particle for the simultaneous encapsulation of hydrophilic and hydrophobic compounds produced by membrane emulsification and solvent diffusion processes

Co-encapsulation of drugs in the same carrier, as well as the development of microencapsulation processes for biomolecules using mild operating conditions, and the production of particles with tailored size and uniformity are major challenges for encapsulation technologies. In the present work, a suitable method consisting of the combination of membrane emulsification with solvent diffusion is reported for the production of multi-core matrix particles with tailored size and potential application in multi-therapies. In the emulsification step, the production of a W/O/W emulsion was carried out using a batch Dispersion Cell for formulation testing and subsequently a continuous azimuthally oscillating membrane emulsification system for the scaling-up of the process to higher capacities. In both cases precise and gentle control of droplet size and uniformity of the W/O/W emulsion was achieved, preserving the encapsulation of the drug model within the droplet. Multi-core matrix particles were produced in a post emulsification step using solvent diffusion. The compartmentalized structure of the multicore-matrix particle combined with the different chemical properties of polycaprolactone (matrix material) and fish gelatin (core material) was tested for the simultaneous encapsulation of hydrophilic (copper ions) and hydrophobic (α-tocopherol) test components. The best operating conditions for the solidification of the particles to achieve the highest encapsulation efficiency of copper ions and α-tocopherol of 99 (± 4)% and 93(± 6)% respectively were found. The multi-core matrix particle produced in this work demonstrates good potential as a co-loaded delivery system.

Novel Membrane Emulsification Method of Producing Highly Uniform Silica Particles Using Inexpensive Silica Sources

A membrane emulsification method for production of monodispersed silica-based ion exchange particles through water-in-oil emulsion route is developed. A hydrophobic microsieve membrane with 15 μm pore size and 200 μm pore spacing was used to produce droplets, with a mean size between 65 and 240 μm containing acidified sodium silicate solution (with 4 and 6 wt% SiO2) in kerosene. After drying, the final silica particles had a mean size in the range between 30 and 70 μm. Coefficient of variation for both the droplets and particles did not exceed 35%. The most uniform particles had a mean diameter of 40 μm and coefficient of variation of 17%. The particles were functionalised with 3-aminopropyltrimethoxysilane and used for chemisorption of Cu(II) from an aqueous solution of CuSO4 in a continuous flow stirred cell with slotted pore microfiltration membrane. Functionalised silica particles showed a higher binding affinity toward Cu(II) than non-treated silica particles.

Pharmaceutical Particles Design by Membrane Emulsification: Preparation Methods and Applications in Drug Delivery

Nowadays, the rational design of particles is an important issue in the development of pharmaceutical medicaments. Advances in manufacturing methods are required to design new pharmaceutical particles with target properties in terms of particle size, particle size distribution, structure and functional activity. Membrane emulsification is emerging as a promising tool for the production of emulsions and solidified particles with tailored properties in many fields. In this review, the current use of membrane emulsification in the production of pharmaceutical particles is highlighted. Membrane emulsification devices designed for small-scale testing as well as membrane-based methods suitable for large-scale production are discussed. A special emphasis is put on the important factors that contribute to the encapsulation efficiency and drug loading. The most recent studies about the utilization of the membrane emulsification for preparing particles as drug delivery systems for anticancer, proteins/peptide, lipophilic and hydrophilic bioactive drugs are reviewed.