Experimental and modelling studies of process intensification for the solvent-antisolvent precipitation of nanoparticles in a spinning disc reactor

Ph. D. Thesis.Solvent-antisolvent precipitation is a key process in pharmaceuticals industries. This research concerns solvent-antisolvent precipitation of starch nanoparticles in the spinning disc reactor (SDR), based on a combination of both experimental and modelling studies. The SDR’s ability to use surface rotation to improve micromixing within thin liquid films, as well as its capability to exhibit near plug flow characteristics is the primary motivation to investigate this process intensification technology for solvent-antisolvent precipitation. One of the objectives of this study is to highlight and understand interactions of the disc surface topography with conditions such as flowrate, solvent-antisolvent ratio and disc speed and their impact on the mixing and precipitation processes. Smaller nanoparticles with narrow particle size distributions (PSDs) were produced as flow rate increased from 6 to 18 mL/s (248 to 175 nm) and disc speed increased from 400 to 1200 rpm (234 to 175 nm). This is attributed to increased shear and instabilities within the liquid film, enhancing mixing as the liquid travels outwards on the disc surface. Increasing the antisolvent to solvent ratio from 1:1 to 9:1 also caused a reduction in size (276 to 175 nm), as greater supersaturation was generated at reduced solubilities, causing nucleation to dominate over particle growth. The disc texture did not significantly affect nanoparticle size; however, particles produced on the grooved disc were of narrower PSD with higher yields. Nucleation rates were determined for the precipitation of starch nanoparticles in the SDR. Nucleation rates increased with an increase in flow rate and disc speed but were a weak function of antisolvent to solvent ratio. The nucleation rate was greater on the grooved surface at the poorer precipitation conditions, as the precipitation then relied primarily on better mixing through the eddies generated by the grooved surface. A maximum nucleation rate of 6.44x1016 mL-1 s -1 was estimated at conditions of 1200 rpm, 9:1 ratio and 15 mL/s, on the smooth disc. Finally, experimentally obtained nucleation kinetics along with growth kinetics have been applied to formulate a predictive PSD model, combining the population balance equations (PBE) with a micromixing model. The model uses Hounslow’s discretisation method to solve the PBEs, accounting for nucleation, growth, and agglomeration in the SDR. Validation of the simulated PSDs has been done through comparison against experimental results. The modelled PSDs are in good agreement with the experimental result

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Shear-Thinning Effect of the Spinning Disc Mixer on Starch Nanoparticle Precipitation

Spinning disc technology is capable of achieving intensified micromixing within thin liquid films created through large shear rates, typically of the order of 103 s−1, generated by means of fast disc surface rotation. In this study the effect of the high shear on solvent–antisolvent mixing and starch nanoparticle precipitation is reported. Rheological studies of starch solutions at 2% w/v and 4% w/v have demonstrated their shear-thinning behaviour at the large shear rates experienced on the spinning disc surface. The effect of such high shear rate on starch nanoparticle precipitation is investigated alongside solute concentration and several other operating parameters such as flow rate, disc rotational speed, and solvent/antisolvent ratio. A reduction in nanoparticle size has been observed with an increase in starch concentration, although agglomeration was found to be more prevalent amongst these smaller particles particularly at larger flow rates and disc rotational speeds. Micromixing time, estimated on the basis of an engulfment mechanism, has been correlated against shear rate. With fast micromixing of the order of 1 ms observed at higher shear rates, and which are practically unaffected by the starch concentrations used, micromixing is not thought to be influential in determining the particle characteristics highlighted in this work

Production of starch nanoparticles through solvent-antisolvent precipitation in a spinning disc reactor

The spinning disc reactor (SDR) uses surface rotation to produce thin film flow with improved mixing and reduced residence times in chemical processing applications. Solvent-antisolvent precipitation is one such process that can benefit from these properties. This study investigates the film hydrodynamics and precipitation of starch nanoparticles by contacting starch dissolved in sodium hydroxide with ethanol as the antisolvent. One objective of this study is to understand how interactions of the disc surface topography (grooved and smooth) with other parameters such as liquid flowrate, antisolvent to solvent flow ratio and disc speed impact the mixing and precipitation processes. Results indicate that an increase in flow rate and rotational speed leads to smaller nano-particles and narrower size distributions, which is attributed to increased shear and instabilities within the liquid film. It was also observed that an increased antisolvent to solvent ratio caused a reduction in particle size, as increased antisolvent generated higher supersaturation. Results showed that although particle size was not significantly influenced by the disc texture, the size distribution was narrower and higher yields were obtained with the grooved disc surface. The grooved disc therefore offers the opportunity for higher throughput in the solvent-antisolvent precipitation of starch particles with better product quality