Experimental and numerical analysis of a sedimentation forming compressible compacts

Batch sedimentations of the mineral talc suspended in water at various initial concentrations resulted in compacts that displayed compression, and compression with channel formation. During the experiments the local concentration was deduced by means of local electrical resistance measurement. The technique provided concentrations that integrated throughout the vessel to give masses that matched the known initial mass employed to within ±5%. Two types of channel zones were observed: soft and hard, the former appeared to be due to the liquid inertia of water discharging from the latter. The region within and above the soft channel zone diluted from the initial concentration, and this caused the visible interface between the suspension and the supernatant to accelerate. The top of the hard channel zone followed the line of constant solids concentration representing the first significant increase in concentration over the initial suspension. A finite difference numerical model of sedimentation matched the experimental data, including the data determined below the visible interface, with very high precision for the talc suspensions exhibiting compression with insignificant channeling. The implicit model was implemented on a conventional computer spreadsheet package and rapidly converged. The model did not employ a function for hydraulic permeability, instead a linear function between the so-called Kozeny “constant” (or coefficient) and concentration was used. In order to provide an accurate numerical model for compressible sedimentation with significant channel formation, the hydraulic permeability needs to be augmented, or the Kozeny coefficient reduced, and the dilution above the channel zone must be predicted. These should be achieved in a way that is general to all sedimentations of a given type of material, and not specific to only one starting concentration. Experimental and numerical results also indicate that the buoyancy force experienced by the solids is adequately described by the density difference between the solids and the suspending liquid, and not the density difference between the solids and the suspension

Membrane emulsification: droplet size and uniformity in the absence of surface shear

A series of tests with membrane pore sizes between 7 and 60 μm and uniform spacing between the pores of 80 and 200 μm, conducted under conditions of zero surface shear at the membrane, show that an additional force to the buoyancy and capillary forces exists in membrane emulsification. A push-off force, derived by consideration of the geometry of the drops as they deform at the surface of the pores under high injection rates when most of the pores are passing liquid, is shown to model the size of the drops formed in the emulsification. In the tests, sunflower oil was injected into water and as the emulsification injection rate increased it was noticeable that there was a point at which the resulting drop distribution is at its narrowest. For the two pore spacings studied: 80 and 200 μm, the point at which the distribution was at its narrowest was at a Weber number of 1.5 × 10−2, where the Weber number is defined using the drop diameter rather than the pore diameter

PLGA particle production for water soluble drug encapsulation: degradation and release behaviour

Particles for subcutaneous depot use encapsulating a model water soluble drug have been produced from poly(lactic-glycolic acid) (PLGA) using a membrane emulsification – solvent evaporation technique. The release behaviour, mainly the change in size and inner morphology are reported. During release, the particles initially swelled in size, then reduced. A diffusion based model, taking in to account the change in particle size, is presented. Surface erosion is evident from the particle size and image evidence, and the diffusion model provides a fit to the data even during the surface erosion period, suggesting that the model drug diffuses before the particle degrades

Preparation and characterization of PLGA particles for subcutaneous controlled drug release by membrane emulsification

Uniformly sized microparticles of poly(DL, lactic-co-glycolic) (PLGA) acid, with controllable median diameters within the size range 40 to 140 microns, were successfully prepared by membrane emulsification of an oil phase injected into an aqueous phase, followed by solvent removal. Initially, simple particles were produced as an oil-in-water emulsion, where dichloromethane (DCM) and PLGA were the oil phase and water with stabiliser was the continuous phase. The oil was injected into the aqueous phase through an array type microporous membrane, which has very regular pores equally spaced apart, and two different pore sizes were used: 20 and 40 microns in diameter. Shear was provided at the membrane surface, causing the drops to detach, by a simple paddle stirrer rotating above the membrane. Further tests involved the production of a primary water-in-oil emulsion, using a mechanical homogeniser, which was then subsequently injected into a water phase through the microporous membrane to form a water-in-oil-in-water emulsion. These tests used a water soluble model drug (blue dextran) and encapsulation efficiencies of up to 100% were obtained for concentrations of 15% PLGA dissolved in the DCM and injected through a 40 micron membrane. Solidification of the PLGA particles followed by removal of the DCM through the surrounding aqueous continuous phase. Different PLGA concentrations, particle size and osmotic pressures were considered in order to find their effect on encapsulation efficiency. Osmotic pressure was varied by changing the salt concentration in the external aqueous phase whilst maintaining a constant internal aqueous phase salt concentration. Osmotic pressure was found to be a significant factor on the resulting particle structure, for the tests conducted at lower PLGA concentrations (10 and 5% PLGA). The PLGA concentration and particle size distribution influence the time to complete the solidification stage and a slow solidification, formed by stirring gently overnight, provided the most monosized particles and highest encapsulation efficiency

Membrane emulsification using membranes of regular pore spacing: droplet size and uniformity in the presence of surface shear

During membrane emulsification it is shown that the size of the drops formed at the membrane surface may increase with increasing dispersed phase injection rate through the membrane, or it may decrease, depending on the prevailing conditions. This is illustrated using a paddle stirrer positioned above flat disc membranes with regular arrays of pores of 20 μm diameter and spacing between the pores of 80 and 200 μm. In the former case an additional mechanism for drop detachment is the push-off force, which is determined by the geometry of the drops as they deform at the membrane surface. When dispersing sunflower oil in to aqueous solutions containing Tween 20, drop sizes between 60 and 200 μm were produced, and in the case of the membrane when the push-off force was working the Coefficient of Variation of the drops formed was below 10%. The push-off force may be added to the shear-drag force to predict drop detachment. For the 200 μm pore spaced membrane this force is much less prominent than the 80 μm spaced membrane. The capillary-shear model has been modified to include this push-off force. The experimental study required the use of very low dispersed phase injection rates as well as very high rates. Hence, two different types of pumps were used to provide these: a peristaltic and syringe pumps. A small study comparing the drop size, and size distributions, showed that the pump type did not influence the drops produced by the membrane emulsification process

The passage of deforming drops through a slotted microfilter

In the flow of a deforming drop through a slotted pore, such as during the microfiltration of oil drops suspended in water, the mechanism for the convection of the oil drops is liquid drag caused by permeate flow through the filter. If the slot is designed to have a converging inlet section then it is possible to estimate the force on the drop from the liquid drag and determine where the drop comes to rest within the converging slot. This equilibrium position is established due to a balance of forces between the liquid drag and the force required to deform the drop to create a larger surface area as the drop becomes less spherical. Experimental measurements are presented for a bubble deforming within an aqueous flow field and a paraffin oil flow field, together with results for the motion of a paraffin oil drop within an aqueous flow field. The data is correlated using a ratio of drop to channel diameter (analogous to slot width) against superficial liquid velocity. Different curves are provided depending only on the physical properties of the fluids used. An analytical mathematical development predicts these curves to a good degree of reliability, which can then be used to predict the oil drop size that is 100% rejected during the filtration of oil drops on slotted microfiltration membranes. Experimental evidence is presented to support the prediction using the filtration of a crude oil on a slotted microfilter with a minimum pore width of 5 microns

Stirred cell membrane emulsification and factors influencing dispersion drop size and uniformity

Water-in-oil (w/o) and oil-in-water (o/w) emulsions were generated using 30-μm pore diameter surface membranes to investigate the factors influencing drop size, and the degree of uniformity of drop size distribution, using a stirred cell employing a simple paddle mounted above a circular disc membrane. The importance of the transitional radius, which is the radius at which the vortex around the unbaffled paddle stirrer changes from a forced vortex to a free vortex and the shear stress at the membrane surface below the stirrer is at its greatest, is demonstrated. Monosized emulsions were produced, with drop size distribution coefficient of variation values of 10% for o/w emulsions and 13.5% for w/o emulsions. These tests demonstrated that a membrane of reduced annular operating area (ringed membrane) produced a more monosized o/w emulsion than a membrane where the full area was used to generate the emulsion, without affecting the mean drop size. The improved size distribution was achieved while the transitional radius was located within the ringed annular section of the membrane. The force balance model, applied to drops formed at the surface of the membrane during emulsification, predicted the droplet diameter provided further drop break up within the stirred cell did not occur. Drop break up occurred at Reynolds numbers below 300 for both oil-in-water and water-in-oil dispersions. Therefore, for Reynolds numbers greater than this, an annular radial ring membrane can be designed to produce monosized droplets using the stirred cell at known continuous phase viscosities with predictable mean droplet size. This knowledge can be used as a design tool to produce monosized droplets of a specified size for various applications using simple stirred cell emulsification

Liquid-liquid membrane dispersion in a stirred cell with and without controlled shear

Oil was passed through membranes into a continuous water phase containing a surfactant (Tween 20) to form oil dispersions with drop diameters between 40 and 400 μm. Two types of stirred equipment were used:  a Weissenberg rheometer (cone and plate geometry) providing constant shear stress at all radial positions which was modified to include a membrane instead of the plate and a simple stirred cell, with a paddle rotating above the membrane, providing variable shear with radial position. Experiments show that the simple paddle-stirred cell provided an oil drop dispersion that was as monosized as that produced by the controlled shear device, if not better. An analysis indicated that only the section of the membrane close to the radius of the highest shear under the paddle stirred membrane produced oil drops. The membranes used in the experiments contained a regular array of nontortuous pores uniformly spaced and provided oil injection rates up to 1000 L m-2 h-1, which is much higher than reported fluxes for the alternative tortuous pore channel membranes made by sintering

Membrane emulsification for the production of uniform poly-N-isopropylacrylamide-coated alginate particles using internal gelation

Alginate particles, crosslinked by calcium ions, have a number of potential biopharmaceutical industry applications due to the biocompatibility of the materials used and formed. One such use is as microcarriers for cell attachment,growth and then detachment without the use of proteolytic enzymes. A straightforward and reproducible method for producing uniform calcium alginate particles with controllable median diameters which employs membrane emulsification and internal gelation (solid particles contained in the dispersed phase) is demonstrated, as well as functionalisation of the resulting beads with amine terminated poly N-isopropylacrylamide (pNIPAM) to form temperature responsive particles, by taking advantage of the electrostatic interaction between the carboxyl groups of the alginate and amino groups of the modified pNIPAM. Cell attachment, growth and detachment capabilities of these core–shell structures were assessed and successfully demonstrated by using phase contrast microscopy and fluorescent staining with calcein-AM and ethidium homodimer-1.The formulation used for the alginate particles avoided non-GRAS chemicals by only using food grade and pharmaceutical grade reagents. The median particle size was controllable within the range between 55 m and 690 m and the size distributions produced were very narrow: ‘span’ values as low as 0.2. When using a membrane pore sizeof 20 m no membrane blockage by the suspended calcium carbonate necessary for internal gelation of the alginate particles was observed. Membrane pore openings with diameters of 5 and 10 m were also tested, but blocked with the 2.3 m median diameter calcium carbonate solids

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7–34 μm and was controlled by the PRX concentration in the feed solution (15–25 g L¯¹), antisolvent/solvent volume ratio (5–30), and type of antisolvent (Milli-Q water or 0.1–0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L¯¹ PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals