Now showing 1 - 3 of 3
  • Publication
    Concentric Annular Liquid-Liquid Phase Separation for Flow Chemistry and Continuous Processing
    A low-cost, modular, robust, and easily customisable continuous liquid-liquid phase separator has been developed that uses a tubular membrane and annular channels to allow high fluidic throughputs while maintaining rapid, surface wetting dominated, phase separation. The system is constructed from standard fluidic tube fittings and allows leak tight connections to be made without the need for adhesives, or O-rings. The units tested in this work have been shown to operate at flow rates of 0.1 – 300 mL/min, with equivalent residence times from 80 to 4 seconds, demonstrating the simplicity of scale-up with these units. Further scale-up to litre per minute scales of operation for single units and tens of litres/minute through limited numbering up should allow these low cost concentric annular tubular membrane separators to be used at continuous production scales for pharmaceutical applications for many solvent systems. In principle this approach may be sufficiently scalable to be utilized in-line, in batch pharmaceutical manufacturing also, through further scale-up and numbering up of units. Several solvent systems with varying interfacial tensions have been investigated, and the critical process parameters affecting successful separation have been identified. An additively manufactured diaphragm based back pressure regulator was also developed and printed in PEEK, allowing highly accurate, adjustable, and chemically compatible pressure control to be accessed at low cost.
      281Scopus© Citations 3
  • Publication
    Spray Encapsulation as a Formulation Strategy for Drug-Based Room Temperature Ionic Liquids: Exploiting Drug−Polymer Immiscibility to Enable Processing for Solid Dosage Forms
    Active pharmaceutical ingredient (API)-based ionic liquids (API-ILs) present an exciting new paradigm for the formulation of poorly water-soluble drugs. In this study, a model room temperature API-IL (1-butyl-3-methyl imidazolium ibuprofenate) was demonstrated to be not just highly soluble but fully miscible and hence have effectively unlimited solubility in water, compared to 0.021 mg mL–1 solubility for the ibuprofen API. Solutions of the API-IL were found to be stable for up to 2 years, indicating that they have the potential to offer thermodynamic stability upon release, avoiding in vivo recrystallization issues that can limit the bioavailability of amorphous solid dispersions (ASDs) and some high-energy crystalline forms. The ibuprofen API-IL was successfully spray-dried into a polymer carrier in loadings of up to 75% w/w in order to transform it into a solid powder suitable for oral solid dosage (OSD) formulation. From modulated differential scanning calorimetry, hot-stage microscopy, powder X-ray diffraction, and attenuated total reflectance Fourier transform infrared spectroscopy measurements, the mechanism by which this high loading was achieved is based on the immiscibility between the polymer and API-IL, with the polymer encapsulating the phase-separated API-IL. Dissolution studies showed that solidification of the API-IL into microcapsules by spray drying in this manner had no detrimental effect on release characteristics. Failure to dissolve crystalline API forms into the polymer matrix eliminates the solubility enhancement of ASDs but not for highly soluble or fully miscible API-ILs. Furthermore, miscible API-IL/polymer dispersions at high loadings were found to possess less-favorable physical properties because of melting point depression, resulting, in some cases, in a failure to form a viable powder. As such, microencapsulated API-ILs at high loadings in immiscible or low-miscibility polymers that have solubility enhancement of the API-IL form, while providing solid powders for processing, represent a promising new platform for the formulation of poorly soluble compounds as OSDs.
      162Scopus© Citations 12
  • Publication
    3D printing of PEEK reactors for flow chemistry and continuous chemical processing
    Chemically resistant parts for flow chemistry, with integrated mixing elements have been produced using the 3D printing process of fused filament fabrication, from poly(etheretherketone). Poly(etheretherketone) has greater chemical resistance than common fused filament fabrication materials such as acrylonitrile butadiene styrene, polypropylene, or even high-performance plastics like poly(etherimide), in addition to having superior thermal resistance and excellent mechanical strength. Printed reactors were demonstrated to be suitable for liquid–liquid extraction and flow chemistry and to be capable of withstanding pressures of at least 30 bar allowing superheated solvents to be used. Burst tests in simple geometries of 20 minute duration have indicated that increased operating pressures of up to 60 bar could be accommodated in future reactor designs. The ability to use fused filament fabrication for these reactors allows highly customisable, cost effective flow reactors and equipment to be fabricated on relatively inexpensive benchtop scale printers. X-ray microcomputed tomography was utilised to non-invasively image and verify the internal structure of the prints to ensure fidelity in reactor fabrication. This non-invasive method of equipment validation shows potential in helping to demonstrate regulatory compliance for bespoke additively manufactured components, for example in continuous pharmaceutical manufacturing where the methods and printer used in this work should be sufficient to produce, (continuous) manufacturing scale equipment.
      600Scopus© Citations 38