Scientific Papers

D. Miramontes Subillaga, S. Heinert, J. Weissbrodt, M. Dragosavac

Complex coacervation is a phase separation process in which two oppositely charged polymers or macromolecules in a solution come together at the liquid-liquid interface to form a dense coacervate shell. The process can be employed to encapsulate oil droplets, creating stable microcapsules that protect and control the release of oil while achieving a high encapsulation efficiency of active ingredients. In this work dry coacervate microcapsules of different size and shell thickness were manufactured combining a continuous single pass cross-flow membrane emulsification system and spray drying to obtain a dry powder. A single-pass crossflow membrane emulsification system with a single cylindrical 10 × 100 mm membrane module with 10 μm pore produced emulsion droplets between 71 μm and 114 μm with a dispersed phase (oil content) in the final emulsion between 3.3 and 6.2 vol/vol% and a total emulsion output mass rate between 25.68 kg h−1 – 49.68 kg h−1. Emulsions manufactured by membrane emulsification were nearly monodispersed with the highest span not exceeding 0.68. Addition of maltodextrin to the emulsion prior to spray drying increased the viscosity and prevented the capsules breakage. Microcapsules up to a mean droplet diameter of 113.19 ± 0.81 μm preserved the shell and had a yield up to 78.43 ± 0.97 wt%, a surface oil as low as 9.35 ± 0.88 wt% and an encapsulation efficiency of 71.09 ± 0.87 wt%.

MehdiMaleki, Clément de Loubens, Kaili Xie, Emeline Talansier, Hugues Bodiguel, Marc Leonetti

A way forward for high throughput fabrication of microcapsules with uniform size and mechanical properties was reported irrespective of the kinetic process of shell assembly. Microcapsules were produced using lab-scale emulsification equipment with a micro-engineered membrane in the size range 10–100μm. The shell of the microcapsules was assembled at the water-oil interface by complexation of polyelectrolytes or cross-linking of proteins providing two different kinetic processes. Elasticity of microcapsules was characterized with an automated extensional flow chamber. Process parameters were optimized to obtain suspensions with size variations of 15%. Some strategies were developed to obtain uniform elastic properties according to the kinetics of shell assembly. If kinetics is limited by diffusion, membrane emulsification and shell assembly have to be split into two steps. If kinetics is limited by the quantity of reactants encapsulated in the droplet, variations of elastic properties result only from size variations.

Maria Grazia Francesconi, Matthew J. Bennett, Ian Dobson, David M. Benoit

Utilisation of CO₂ as a chemical reagent is challenging, due to the molecule’s inherent chemical stability. However, CO₂ reacts promptly at high temperature (~1000 °C) with alkaline-earth oxides to form carbonates and such reactions are used towards capture and re-utilisation. In this work, this concept is extended and CO₂ is utilised as a reagent to modify the crystal structure of mixed-metal inorganic solids. Modification of the crystal structure is a “tool” used by materials scientists to tailor the physical property of solids. CO₂ gas was reacted with several isostructural mixed-metal oxides Sr₂ CuO₃ , Sr 1.8 Ba 0.2 CuO₃ and Ba 2 PdO₃ . These oxides are carefully selected to show anion vacancies in their crystal structure, to act as host sites for CO₂ molecules, leading to the formation of carbonate anions, (CO₃ ) 2− . The corresponding oxide carbonates were formed successfully and the favourable formation of SrCO₃ as secondary phase was minimised via an innovative, yet simple synthetic procedure involving alternating of CO₂ and air. We also derived a simple model to predict the kinetics of the reactions for the cuprates, using first-principles density functional theory and assimilating the reaction to a gas–surface process.

Laouini, A, Charcosset, C, Fessi, H, Holdich, RG, Vladisavljevic, GT (2013) Preparation of liposomes: a novel application of microengineered membranes: From laboratory scale to large scale, Colloids and Surfaces B: Biointerfaces, 112, pp.272-278, DOI: 10.1016/j.colsurfb.2013.07.066.

A novel ethanol injection method using microengineered nickel membrane was employed to produce POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and Lipoid® E80 liposomes at different production scales. A stirred cell device was used to produce 73 ml of the liposomal suspension and the product volume was then increased by a factor of 8 at the same transmembrane flux (140 l m−2 h−1), volume ratio of the aqueous to organic phase (4.5) and peak shear stress on the membrane surface (2.7 Pa). Two different strategies for shear control on the membrane surface have been used in the scaled-up versions of the process: a cross flow recirculation of the aqueous phase across the membrane surface and low frequency oscillation of the membrane surface (∼40 Hz) in a direction normal to the flow of the injected organic phase. Using the same membrane with a pore size of 5 μm and pore spacing of 200 μm in all devices, the size of the POPC liposomes produced in all three membrane systems was highly consistent (80–86 nm) and the coefficient of variation ranged between 26 and 36%. The smallest and most uniform liposomal nanoparticles were produced in a novel oscillating membrane system. The mean vesicle size increased with increasing the pore size of the membrane and the injection time. An increase in the vesicle size over time was caused by deposition of newly formed phospholipid fragments onto the surface of the vesicles already formed in the suspension and this increase was most pronounced for the cross flow system, due to long recirculation time. The final vesicle size in all membrane systems was suitable for their use as drug carriers in pharmaceutical formulations.

Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward​

Since their discovery in 1965, by Alec D. Bangham, liposomes have been recognised as the drug delivery vehicle of choice. Their biocompatibility results in minimal adverse reactions. Their amphiphilic structure allows encapsulation of both hydrophilic and hydrophobic active pharmaceutical ingredients (APIs). More recently the liposome’s analogous cousin, the lipid nanoparticle, has gained prominence because of its ability to deliver therapeutic payloads, including DNA and mRNA for vaccines. They can both deliver their payload very precisely through treating their surface with proteins allowing highly specific binding to a target cell type. This paper describes the advantages, over the most common commercial processes, that Micropore's membrane emulsification technology has in Liposomes and Lipid nanoparticle production.

Grace Walden, Xin Liao, Graham Riley, Simon Donell, Michael J. Raxworthy, and Aram Saeed

Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward​

Phase change materials (PCMs) allow the storage of large amounts of latent heat during phase transition. They have the potential to both increase the efficiency of renewable energies such as solar power through storage of excess energy, and to reduce overall energy demand through passive thermal regulation. NASA has identified more than a hundred of these materials. In addition to passive energy storage, they have application in thermo-regulated fabrics, high power electronics, telecommunication installations and microprocessors. PCMs are not suitable for use without prior encapsulation. Encapsulation in a shell material provides benefits including protection of the PCM from the external environment and increased specific surface area to improve heat transfer.

Joanna Wolska and Nasim Jalilnejad Falizi

The membrane emulsification process (ME) using a metallic membrane was the first stage for preparing a spherical and monodisperse thermoresponsive molecularly imprinted polymer (TSMIP). In the second step of the preparation, after the ME process, the emulsion of monomers was then polymerized. Additionally, the synthesized TSMIP was fabricated using as a functional monomer N-isopropylacrylamide, which is thermosensitive. This special type of polymer was obtained for the recognition and determination of trace bisphenol A (BPA) in aqueous media. Two types of molecularly imprinted polymers (MIPs) were synthesized using amounts of BPA of 5 wt.%(MIP-2) and 7 wt.% (MIP-1) in the reaction mixtures. Additionally, a non-imprinted polymer (NIP) was also synthesized. Polymer MIP-2 showed thermocontrolled recognition for imprinted molecules and a higher binding capacity than its corresponding non-imprinted polymer and higher than other molecularly imprinted polymer (MIP-1). The best condition for the sorption process was at a temperature of 35 ◦C, that is, at a temperature close to the phase transition value for poly(N-isopropylacrylamide). Under these conditions, the highest levels of BPA removal from water were achieved and the highest adsorption capacity of MIP-2 was about 0.5 mmol g−1 (about 114.1 mg g−1) and was approximately 20% higher than for MIP-1 and NIP. It was also observed that during the kinetic studies, under these temperature conditions, MIP-2 sorbed BPA faster and with greater efficiency than its non-imprinted analogue.

Jennifer Huen PhD, Beagle Scientific Inc.

When the first liposome-based drug, Doxil®, was approved in the mid-1990s, decades of research spurred the need for more suitable lipid formulations with faster, better controlled and more efficient manufacturing methods. Most recently, the urgency of the COVID19 pandemic pushed the scientific community for larger scale production of the mRNA vaccines with greater consistency—a need that is still evolving. Each of the current methods for industrial production of lipid nanoparticle (LNP) drugs have their unique set of pros and cons. Most liposome drugs are produced by lipid hydration and extrusion, a bulk method that is not suitable for consistent production of LNPs small enough to penetrate tissues for cell entry. From a formulation discovery perspective, microfluidic mixers can quickly produce large LNP libraries while minimizing waste. Yet these mixers cannot accommodate commercial-scale production volumes. Impingement jet mixing (IJM) is the most widespread manufacturing method as it can support high yields through unit parallelization but is less controllable and can potentially compromise LNP stability. Finally, advanced crossflow is a scalable, high efficiency method that has the potential to meet the demands of global disease emergencies. While IJM is currently the method of choice for mRNA vaccine manufacturers, other strategies must not yet be ruled out. As the development of new drug modalities and innovations accelerates, so too must strategies for faster, scalable drug manufacturing.