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Innovations and process understanding is the current focus in pharmaceutical industry. The objective of this research was to explore application of high power ultrasound in the slurry crystallisation and application of low power ultrasound (3.5 MHz) as process analytical technology (PAT) tool to understand pharmaceutical processing such as hot melt extrusion. The effect of high power ultrasound (20 kHz) on slurry co-crystallisation of caffeine / maleic acid and carbamazepine / saccharin was investigated. To validate low power ultrasound monitoring technique, it was compared with the other techniques (PAT tools) such as in-line rheology and in-line NIR spectroscopy. In-line rheological measurements were used to understand melt flow behaviour of theophylline / Kollidon VA 64 system in the slit die attached to the hot melt extruder. In-line NIR spectroscopic measurements were carried out for monitoring any molecular interactions occurring during extrusion. Physical mixtures and the processed samples obtained from all experiments were characterised using powder X-ray diffraction, thermogravimetry analysis, differential scanning calorimetry, scanning Electron Microscopy, dielectric spectroscopy and high performance liquid chromatography, rotational rheology, fourier transform infrared spectroscopy and near infrared spectroscopy. The application of high power ultrasound in slurry co-crystallisation of caffeine / maleic acid helped in reducing equilibrium time required for co-crystal formation. During carbamazepine / saccharin co-crystallisation high power ultrasound induced degradation of carbamazepine was negligible. Low power ultrasound can be used as a PAT tool as it was found to be highly sensitive to the changes in processing temperatures and drug concentration.

In vivo pressure estimations for therapeutic ultrasound has the potential of rendering treatments using non-invasive ultrasound targeting safer and more reliable. By quantifying pressures and their respective spatial locations, better acoustic predictions and models can be made. In this thesis, we aim to measure a pressure field from a piezo-electric transducer through a ballistic gel medium by using an external gradient coil to encode the pressure field in a way that can be read and quantified using an MRI scanner. We describe the methods and the results pertaining to visualizing a pressure field. The setup was able to capture pressure field images and quantify low pressures, as compared to a hydrophone measurement, with maximum peaks of 100 kPa. We found that the confidence interval of the MRI estimated pressure to have a 95% confidence interval of 46 kPa as compared to the hydrophone measurement. We also showed that the MRI measurement setup had an accuracy of 5 kPa within 2 cm from the front of the transducer. The results showed that pressure fields could eventually be reconstructed with precision and accuracies close to that of a hydrophone equivalent acquisition. However, there are still many changes to the methodology that would need to be done.

This work describes the development of an optical probe for measuring movement of tissue particles deep inside which are loaded by an ultrasound remote palpation device. The principle of the method is that ultrasound force which can be applied inside the tissue makes the tissue particles vibrate and this vibration phase-modulates the light intercepting the insoniified region which results in a modulated speckle intensity on detection outside the object. This speckle intensity modulation detected through the measured intensity autocorrelation is a measure of the vibration amplitude. Since the vibration amplitude is related to the local elastic properties of the medium, the measured modulation depth in intensity autocorrelation can be used to map the elastic property in the insonified region. In this work, first the ultrasound induced force is calculated for both plane and focused ultrasound beams, and converted to amplitude of vibration and refractive index modulation, solving the forward elastography equation. Light propagation inside an insonified object is modelled using Monte Carlo simulation and the amplitude and intensity correlations are computed. The modulation depth on the autocorrelation is estimated and shown that it is inversely correlated to the local elastic modulus and optical absorption coefficient. It is further shown that whereas the variation in modulation depth is linear with respect to absorption coefficient, the same variation with elastic property is nonlinear. These results are verified experimentally in a tissue mimicking phantom. The phantom was constructed out of poly vinyl alcohol(PVA) whose optical, mechanical and acoustic properties are independently controlled. It is also shown that for loading with focused ultrasound beam the displacement is almost along the ultrasound transducer axis and therefore the contribution from refractive index modulation alone can be ascertained by probing the insonified perpendicular to the transducer axis. This helps one to find the contribution to the modulation depth from the ultrasound-induced vibration, which can be used to compute a quantitative estimate of the elastic modulus from the modulation depth.

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Current research within the field of ultrasound contrast agents (UCAs) aims at developing capsules which are not only acoustically active, but also have a chemically modifiable surface. This enables use in new areas, including targeted drug delivery and theranostics. For such purposes, air-filled microbubbles (MBs) with a polyvinyl alcohol (PVA) shell are being studied. Ultrasound imaging velocimetry (UIV) is a technique used to evaluate various types of liquid flows by tracking patterns caused by UCAs across ultrasound images, and has shown great potential for flow measurements in terms of accuracy. The aim of this thesis was to implement a basic UIV program in Matlab to investigate the flow behavior of air-filled PVA MBs being pumped through a phantom, mimicking a blood vessel. The images were acquired using the programmable Verasonics research system by plane wave imaging with coherent compounding, and UIV was implemented as a post-processing technique. Three parameters were varied to study how the UIV performance and flow behavior of the MBs were affected: the concentration of MBs, the flow velocity, and the transducer voltage. The resulting velocity vector fields showed that it is possible to track PVA MBs using the implemented UIV program, and that the concentration 5·106 MBs/ml gave the best results out of the five concentrations tested. The generated velocity vector fields indicated a turbulent and pulsatile flow behavior, which was in line with the predicted flow behavior, although there was a disparity between the measured average flow velocity of the MBs and the predicted flow velocity. It was also observed that the MBs were increasingly pushed in the axial direction with increasing voltage, as according to theory. Even though a more advanced UIV algorithm could improve the accuracy of the velocity measurements, the results show possible use of air-filled PVA MBs in combination with UIV. / Nuvarande forskning inom ultraljudskontrastmedel syftar till att utveckla kapslar som inte bara är akustiskt aktiva, utan som även har en kemiskt modifierbar yta. Detta möjliggör användning inom nya områden, så som målinriktade läkemedel och theanostics. För detta syfte studeras luftfyllda mikrobubblor med ett skal av polyvinylalkohol (PVA). Ultrasound imaging velocimetry (UIV) är en teknik som används för att analysera olika typer av vätskeflöden genom att spåra mönster orsakade av ultraljudskontrastmedel över ett antal ultraljudsbilder. Metoden har visats ha stor potential för flödesmätningar, och hög noggrannhet har uppnåtts. Detta projekt syftade till att implementera ett grundläggande UIV-program i Matlab för att undersöka flödesbeteenden hos luftfyllda PVA-mikrobubblor som pumpas genom en modell av ett blodkärl. Ultraljudsbilderna togs med hjälp av det programmerbara forskningssystemet Verasonics, genom att använda planvågsavbildning och coherent compounding, och UIV implementerades som ett efterbearbetningsprogram. Tre parametrar varierades för att studera hur prestandan av UIV-programmet och flödesbeteendet hos mikrobubblorna påverkades: koncentrationen av mikrobubblor, flödeshastigheten, och spänningsamplituden hos ultraljudsproben. De resulterande hastighetsvektorfälten visade det möjligt att evaluera flödesbeteenden hos PVA-mikrobubblor med hjälp av det implementerade UIV-programmet. Bäst resultat erhölls genom att använda koncentrationen 5·106 mikrobubblor/ml, av de fem testade koncentrationerna. De genererade hastighetsvektorfälten indikerade ett turbulent och pulserande flöde, vilket överensstämde med teorin, trots att det fanns skillnader mellan genomsnittliga uppmätta flödeshastigheter och den beräknade flödeshastigheten. Det kunde också observeras att mikrobubblorna trycktes i den axiella riktningen när spänningsamplituden ökade, vilket överensstämde med teorin. Trots att metodens noggrannhet skulle kunna ökas genom att använda ett mer avancerat UIV-program, visade resultaten på möjligheten att använda luftfyllda PVA-mikrobubblor i kombination med UIV.