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Crystal growth ofmiconazole andeconazole, two antimycoticimidazole derivatives, were studied with a view to preventing orlimiting crystal growth in atopical semisolid formulation. Crystal growth of the drugs from alcoholic solution was studied, and a ternary (water - cetostearyl alcohol - cetrimide) gel was prepared and considered as a model topical semisolid, principally using rheology and microscopy. The interaction of the drugs with gel components was studied, including interaction of crystalline drug material with aqueous surfactant solutions, and van't Hoff solubility profiles of drugs in nonaqueous components. The effect of gel quality (found to vary with manufacturing temperature) upon rate of crystal growth and crystalline habit was considered, and comparison was made between crystal growth in a ternary system, and in a similarly formulated semisolid emulsion. A range of molecules were screened as potential inhibitors of miconazole crystal growth in the ternary system, and β-cyclodextrin and Dextran-40 were studied in more detail. The additives reduced the rate of crystal growth and altered the proportion of the two habits, but did not prevent growth of crystals in the gels for any practical length of time. It was found that the appearance of a platy habit of miconazole was related to the development of a layered structure within the gel, and the effect of the additives, both in the bulk water phase, and within the layers of swollen gel phase, was considered.

This thesis is a study of research linkage between industry and academia. It concentrates on the industrial side of these interactions and, in particular, the impact of information flows from academia industrial innovation. Specifically, the study explores the proposition that linkage varies - in extent and nature according to the stage of development of the research field involved. A review of the literature suggested that linkage should be particularly strong in a nascent technology, such as that unfolding currently in biotechnology. The field study involved face-to-face interviews with industrial researchers from UK pharmaceutical companies and from new start-up companies. It was designed in order to ascertain the relative strength of linkages in the new biotechnology; to characterize these linkages; and to explore how they might change as the technology develops. It is ~emonstrated that linkage is indeed strong here, involving lntensive 'search' activities and often substantial formal collaboration with academia. The background material collected - concerning the role of linkage in innovation and in corporate strategies for biotechnology confirm that companies are obliged to 'plug in' to academic research precisely because 'of the dynamism and uncertainty which characterizes a new technological field. It is argued that those pharmaceutical companies which are interacting most with academic research are also those which are most likely to succeed commercially with the new techniques. The start-up companies in biotechnology are shown to have extremely close links with both academia and the large established companies active in the field. It is argued that the very presence of such companies is itself symptomatic of the proximity of academic science and industrial technology in this new field. In conclusion, it is suggested that the pattern of linkage found in biotechnology may well ~ertain in other new science-based fields; some policy lmplications are discussed.

The objective of this work was the investigation of the polymeric interactions in tablet coating films in relation with effective film formulations. The polymeric interactions were studied by means of torsional braid analysis. For this purpose an existing torsional braid analyser was improved and successfully interfaced to a microprocessor for data acquisition and reduction. Discussion on the contribution of the substrate to the thermomechanical spectra of the TBA as well as factors associated with the optimisation of the technique are presented. The dynamic mechanical behaviour of EC, HPMC, HPMCP-HP50, HPMCP-HP55, HPC and CAP film formers was studied with particular attention to structure- Tg relationship. The plasticisation of two of the most common film formers, namely EC and HPMC, with a series of polyethylene glycols was investigated. It was shown that PEGs efficiently plasticise HPMC, whereas they exhibited limited interactions with EC. The relation of the plasticising efficiency to the size and concentration of the PEGs with respect to the optimisation of the tablet coating formulation is also discussed. The thermomechanical behaviour of blends of EC with water-/pH-dependent film formers was also studied with TBA, in conjunction with the requirements for controlled release coatings. All polyblends exhibited phase separation and the required domain morphology, which was shown capable of retaining small amounts of water-/pH-dependent components even after prolonged leaching. Moreover, the modification of the thermomechanical performance of 80/20 w/w EC/HPMC blends plasticised with PEG200 and PEG400 was investigated. These studies indicated diffusion of the plasticisers into both phases. Finally, the effects of blend composition and interactions in terms of efficient sustained release coatings are identified and discussed.

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