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Liquid-core microcapsules: A mechanism for the recovery and purification of selected molecules in different environments

Whelehan, Micheal (2011) Liquid-core microcapsules: A mechanism for the recovery and purification of selected molecules in different environments. PhD thesis, Dublin City University.

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Liquid-core microcapsules can be described as miniature sized particles (< 1 mm in diameter) consisting of a liquid-(core) enveloped completely within a defined porous or impermeable membrane, and can be manufactured from a wide range of natural and/or synthetic materials. These structures usually take a spherical form and have been shown to have many exploitable characteristics in numerous processes. In this study, these particles were used as a tool for the recovery and/or purification of different molecules in their associated environments. The first section of this study was devoted to the characterization of a methodology to manufacture microspheres/microcapsules using an alginate hydrogel as the encapsulation matrix. Due to its many advantages, such as an easy operation and the ability to control droplet size, the vibrating nozzle (jet) technique was chosen as the manufacturing technique. Using the single nozzle system, and a pressurized flow control system to delivery the polymer, it was possible to produce microspheres/spheres, under reproducible conditions, in a size range of 100 μm to 2 mm in diameter, with the produced structures having a standard size deviation of between 1- 1.5%, for any size generated. Whilst the size was mainly dependant on nozzle diameter, it was identified that this feature could be altered further by increasing/decreasing the frequency of the vibration and/or the flow of the polymer. For the concentric system, similar reproducible results were obtained, but due to the more complicated system, brought about by the two-flow mechanism to the nozzle, the size deviation increased to around ± 2.5% in most cases. Due to the separate flows of the outer and inner phases, it was possible to control the core and membrane size of the microcapsules during production, with either being able to occupy between 10-90% of total capsule volume. It was shown throughout this work that this trait can be a very important property, as it can affect the numerous characteristics of capsules, such as: mechanical strength, buoyancy and most importantly for this study, the mass transfer (permeability) of external and/or internal compounds to and from the core of the microcapsules. For both arrangements it is possible to produce > 1.2 l/hr of microspheres and > 2 l/hr of liquid-core microcapsules, and this can be easily and naturally elevated to higher volumes by increasing the number of nozzles on the encapsulator. Firstly the microcapsules were used as an innovative technique (known as capsular perstraction) to recover the commonly found pharmaceutically active compounds; sulfamethoxazole, metoprolol, furosemide, carbamazepine, clofibric acid, warfarin and diclofenac from water. The approach of preparing capsules with different solvents within their cores and combining them in water, contaminated with pharmaceuticals, enabled a rapid recovery of the drugs from this sphere. In addition the uptake of warfarin was examined to assess the conditions affecting mass transfer of the molecules into the capsules. It was subsequently determined that the stagnant organic layer was the main limiting factor. This part of the study emphasized how the characteristics (size and membrane thickness) of capsules can affect the removal rate of compounds into the liquid-core and also how the rate of extraction can be simply controlled by varying these parameters during the capsule manufacturing process. In a second application, the capsular extraction technology was further developed by adopting it as an aide for the recovery and purification of the antibiotic geldanamycin from Bennett’s medium. From this work it was shown how a small quantity of capsules was capable of rapidly extracting the molecule from the culture medium. Again the limitations to mass transfer were accessed, and it was discovered that the main rate limiting step was the external resistance outside of the capsules, which can be governed by controlling the outer turbulence. In a further development the capsules showed their potential to be used as a mechanism for concentrating, purifying and enabling crystallization of the extractant, using a very simplistic and straightforward procedure, which was not destructive to the microcapsules, hence enabling their continuous re-use. Finally the capsules were applied to a real-time situation, in order to examine the feasibility of using the simple, non-toxic and sterile technology as a novel in-situ product recovery technique, to improve the production and recovery yield of geldanamycin in cultures containing the bacterium Streptomyces hygroscopicus. Implementation of this approach resulted in the rapid removal of the metabolite from an environment which was causing its break-down and seriously affecting recovery yields. Extraction enabled the molecule to be transferred into a stable and secure domain, where it was protected from external influences. This removal improved overall net production by 30% compared to fermentations containing no capsules. Most importantly however, the capsule-facilitated recovery process acted as a methodology, which enabled high recoveries (> 53%) of the fermented geldanamycin to be obtained as highly purified crystals (> 97%) using a facile, inexpensive and reproducible process, which should be easily implemented at a lab-scale or industrial-level.

Item Type:Thesis (PhD)
Date of Award:November 2011
Supervisor(s):Marison, Ian
Uncontrolled Keywords:Liquid-core microcapsules; Capsular perstraction; Alginate; Dibutyl sebacate; Oleic acid; Pharmaceutically active compounds; Geldanamycin; In-situ product recovery; Downstream processing
Subjects:Biological Sciences > Biotechnology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
ID Code:16649
Deposited On:30 Nov 2011 10:32 by Ian Marison. Last Modified 30 Nov 2011 10:32

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