Investigations on the mechanisms of non-photochemical laser-induced nucleation and sonocrystallisation

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2022
Thesis identifier
  • T16397
Person Identifier (Local)
  • 201557668
Qualification Level
Qualification Name
Department, School or Faculty
  • In recent years, a number of authors have steered Non-Photochemical Laser-induced Nucleation (NPLIN) and sonocrystallisation from mystery towards viable and valuable application for improved control over the industrial crystallisation of drug substances. However, the underlying mechanisms of nucleation induction from the phenomena generated by laser irradiation and ultrasonic wave propagation are both still under investigation. So far, a complex picture of bubbles and localised pressure fluctuations at the interplay of clusters and crystals has been provided. This thesis presents detection of bubble fields in order to provide mechanistic insight into NPLIN and sonocrystallisation. On the underlying mechanisms of the NPLIN effect, doubts have been cast on the initially proposed effects of the optical electric field acting directly upon solute clusters. Recently, it has been proposed that at laser pulse energies below the threshold for optical breakdown of the liquid, impurity particle heating generates transient vapour cavities, the associated phenomena of which provide opportune conditions for nucleation induction. However, there have been a lack of experimental attempts to detect vapour cavities in order to support this mechanism. Chapter 4 provides significant evidence of nucleation induction within an unfocused beamline via cavitation generated by particle heating. For the first time, single-pulse (1064 nm, 6ns) laser-induced nucleation of ammonium chloride was captured with high-speed imaging. Observations at 100000 fps allowed for the detection of multiple micron-sized bubbles before the appearance and growth of multiple primary crystal nuclei within the irradiated volume of the solution. Further compelling evidence for the impurity particle-heating mechanism is provided by needle hydrophone measurements, in which the effect of solute concentration alongside solution filtration and iron oxide nanoparticle doping prior to irradiation were investigated. Signal processing allowed for quantification of the broadband noise produced by bubbles that were generated on laser irradiation. Overall, the results demonstrate a direct relationship between absorbing particles, cavitation generation and crystal nucleation, which has powerful implications for discussions behind the mechanism for laser-induced nucleation. The effects of propagating ultrasound waves through a liquid occur via the generation of acoustic cavitation: the growth and collapse of vapour cavities under an applied ultrasound field. This mode of cavitation generation is well established for inducing crystal nucleation and fragmentation. However, few previous sonocrystallisation studies have involved measurement of cavitation activity in the generated sound field. Moreover, the physical properties of a liquid have been reported to significantly affect the cavitation activity, under the same applied ultrasound parameters. Chapter 5 presents a comparison of cavitation activity in typical crystallisation solvents, under a high-power ultrasound field. A setup was established in order to perform needle hydrophone measurements, from which the acoustic pressure and broadband integrated voltage were obtained at increasing drive powers. The broadband noise measurements are discussed in relation to the solvent physical properties. Previous paracetamol (PCM) sonocrystallisation studies involving the application of highpower ultrasound fields have reported (i) the selective crystallisation of the elusive metastable form II and (ii) higher impurity rejection in the presence of acetanilide and metacetamol, both on comparison with silent conditions. However, the mechanisms behind these observations remain unclear. Chapter 6 provides an investigation of PCM cooling sonocrystallisation, with a focus on the mechanisms for polymorphism and purity effects. It was established that, under the same applied frequency, the selective crystallisation of form II relied upon the application of cavitation energy above a threshold, together with both high supersaturation and rapid growth conditions. Meanwhile, greater impurity purging with cavitation generation was attributed to nucleation induction at significantly lower supersaturation levels, as opposed to cavitation phenomena promoting impurity rejection. Moreover, a morphology change from equant to columnar crystals of PCM form I was observed in the presence of impurities only under an applied cavitation field, which was attributed to the acceleration of surface integration caused by stable cavitation phenomena. This effect has not before been reported and it is expected to influence the development of industrial sonocrystallisation processes for drug substance purification.
Advisor / supervisor
  • Price, C. J. (Chris J.)
  • O'Leary, Richard
Resource Type
  • Error on title page. Date of award is 2022.