Novel Imaging Applications for Pharmaceutical Materials and Formulations

This thesis presents a novel investigation into the use of two advanced imaging techniques in the field of pharmaceutics. The first is surface dissolution imaging(SDI).This technique utilises ultra-violet (UV)light and a Complementary Metal Oxide Semiconductor(CMOS)detector chip to image and film a wide range of dissolution phenomena. The second technique is focus variation microscopy(FVM).This powerful light microscope combines conventional microscopy with vertical scanning allowing for both high resolution images and surface topography data to be obtained. The introduction of this work thus provides a brief history and review into the design and development of dissolution imaging and the wide range of research that has currently been conducted. An introduction in to surface texture measurement and focus variation microscopy are also given to give the reader context as to how these are used in the detailed research.

This thesis focuses on the second generation of the surface dissolution instrument (SDi2) which has an additional dosage cell, compared to its predecessor the SDI300,and the ability to record images in both the UV and visible ranges simultaneously. Chapter 3 therefore details and describes the development of a methodology that allows the utilisation of dissolution imaging for the purposes of monitoring accurate swelling of hydrophilic matrices. The successful results showed a set of specific parameters needed to be followed in relation to both absorbance threshold and the width of the measurement zone. This developed method was also successfully used in the swelling determination of other hydrophilic polymeric matrices in chapter 4. The results also showed this methodology to be a material sparing technique as compared to the traditional methods of investigating swelling processes.

Chapters 5-7 uses gemfibrozil (GEM),indomethacin (INDO) and propranolol hydrochloride as model drugs in salt formation, solid dispersions and liquisolid compact formulations. Focus variation is used in understanding the surfaces that are prepared prior to intrinsic dissolution rate determination (IDR). Techniques such as X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC)and scanning electron microscopy (SEM) were used for salt and solid dispersion confirmation as well as morphological characterisation. The results from the focus variation for both the salts and solid dispersions indicated that compacts prepared for IDR determination picked up the tooling “imprint” on the surfaces which can impact on IDR values obtained. A web-like phenomenon was also observed for the solid dispersions during IDR imaging which seemed to increase with increasing polymer content. This process explained the lower IDR values obtained for the solid dispersion relative to that of the “pure drug (INDO)”. The use of the whole dose cell showed the dissolution of the solid dispersion to increase with increasing polymer content. Chapter 7 also recorded the first simultaneous drug release and swelling of liquisolid compacts.

The information from this thesis therefore demonstrates the versatility and use of both imaging techniques in providing vital information for the formulator in the early stages.