Electrospray scale-up for the production of particles of pharmaceutical interest
- Autores: Nikolas Sochorakis
- Directores de la Tesis: Joan Rosell Llompart (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Ignacio González Loscertales (presid.), Ricard Garcia Valls (secret.), Urszula Stachewicz (voc.)
- Programa de doctorado: Programa de Doctorado en Nanociencia, Materiales e Ingeniería Química por la Universidad Rovira i Virgili
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Electrospray provides unique atomization of liquids, whereby micro- or nano-droplets with very narrow size distributions are generated. To scale up this process, many electrospray emitters must be operated while keeping the flow rate per emitter unchanged to preserve stability. We have studied the conditions leading to robust spraying in linear arrays of electrosprays in which a row of thin tubes (emitters) protrude out of a backplate, and face a flat collector plate (counter electrode) set at a high negative potential. The counter electrode is far compared to the inter-emitter separation. Strong electrostatic interactions are expected between the spray plumes and the electrified liquid menisci which are attached to the emitters (Taylor cones). In addition, electrodes at both ends of the array enable uniform electrical field conditions, while preventing electrical gaseous discharges. We show that this geometry is scalable without bound, by experiments performed under different geometrical configurations, liquid flow rates per emitter, and electrical conductivities of the liquid (mainly, NaCl/MEG solutions). The onset voltage required to stabilize the spraying at all emitter positions approaches a plateau as the number of operated emitters increases. This conclusion is in agreement with electric field computations in simplified geometries.
The same electrospray setup has been used to generate polymer micro/nano particles loaded with an active pharmaceutical ingredient (API). Our model API is turmeric, a potent anti-inflammatory natural substance which is water insoluble, and therefore suffers from low bio-availability. An ethanol solution of this API and a highly hydrophilic polymer (polyvinylpirrolidone, PVP) has been electrospray dried using the linear electrospray array, resulting in PVP-turmeric spherical particles of 0.5 μm average size. Micronized particles of a hydrophilic polymer-API formulation can be used in drug delivery for improving the bioavailability of poorly water-soluble APIs. Position sensitive analysis at areas of interest (AOI) in each collection spot has been performed using scanning electron microscopy (SEM) to identify the distribution of sizes and morphology of the deposited micro-particles, revealing good reproducibility spot to spot and across different batches. The particles accumulate over time on the collector, below each of the emitters, producing macroscopical 2D-ovoidal deposition spots. The spots are poorly aligned due to the electrostatic interaction between the spray-plumes (especially the neighboring ones). We show that the spots diverge from the array plane, amplifying any minute misalignment of the emitters within the linear array. An horizontal electrode configuration has been implemented to restore the symmetry of the deposition spots. Apart from a silicon wafer used as particles collection substrate, we show that it is possible to collect particles directly on paper, at ambient conditions, interesting also in the context of our next application.
Not only is paper a common, cheap and biodegradable material; it has attracted much interest as a substrate for microfluidics and biomedical assays. It is the perfect candidate for the development of low cost biosensors in the form of lateral flow assays for point-of-care diagnostics. We have developed a single emitter electrohydrodynamic (EHD) jet printing device that can jet-print lines directly on cellulose or nitrocellulose paper with no prior treatment. The “inks” are water based protein solutions without any other polymer addition. The advantage of our method is that the size of the printed features are several times smaller than the emitter capillary size preventing clogging. We have tackled the issue of stabilizing a cone-jet for a water based solution, using a laminar co-axial gas co-flow around the EHD emitter. In addition, for the final lateral flow assembly we have used a novel modular DNA- binding protein which can be modified to detect different DNA targets. Upon detection, the assays produce a colorimetric signal in the form of a line on the nitrocellulose paper strip. As a conclusion, we have successfully printed a nitrocellulose paper-based biosensor for the detection of the human papilloma virus-DNA target.
