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Preparation and isolation of drug particles with improved therapeutic response

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dc.contributor.advisor Hudson, Sarah P.
dc.contributor.advisor Rasmuson, Åke C. Tierney, Teresa B. 2018-08-30T09:08:49Z 2018-08-30T09:08:49Z 2016
dc.description peer-reviewed en_US
dc.description.abstract Crystals of a particular size and habit can be engineered by manipulating crystallisation process conditions. In the pharmaceutical industry, size control of the final drug product is vital for preparing a medicine with a specific therapeutic outcome. This work focuses on controlling the crystal size and shape of drugs with limited aqueous solubility, so that upon oral administration, they will dissolve at a desirable rate in the aqueous environment of the gastrointestinal tract, thus allowing efficient delivery of their therapeutic response. Crystals of salicylic acid and fenofibrate were prepared at nano and/or micron size ranges by antisolvent-based precipitations from supersaturated solutions. The outcome in terms of particle size and shape depended on the mass available, the degree of supersaturation and the choice of stabilising additives employed during the preparation process. Micro-particles of salicylic acid were prepared at supersaturations < 8 with sizes ranging from 20-150 μm for the pure system and as low as 6 μm for an additive-stabilised system. Selection of a supersaturation of > 3000 facilitated generation of nanosized particles of fenofibrate. In their suspended state, the nanoparticles dissolved instantaneously upon addition to the dissolution medium. However, as a result of their small size the particles were physically unstable and grew into the micron size range within 2 min, leaving a limited time window for their isolation from suspension into the solid state. Solubilised additives (eg. PVA) were capable of stabilising the nanoparticles in suspension and extending the time period over which the particles remained at the nano size range. However, isolation and drying of these small, fragile and highly energetic systems by freeze-drying presented further difficulties, with drying-induced aggregation and fusion causing the nanoparticles to forego their nanoparticle-induced dissolution enhancement. An alternative, all in one, stabilisation and isolation strategy was developed to overcome the primary challenges associated with nanoparticle formulations. Surface-functionalised insoluble, micro-scale carrier particles were designed to attract drug nanoparticles from suspension onto their surface. Carrier-attached nanoparticles were stable from growth and aggregation both in suspension and during drying. A simple filtration step was sufficient to separate the nanoparticle-carrier composites from suspension, to produce a solid-state material which maintained its nanoparticle-induced fast dissolution rate. The process was successfully demonstrated with two BCS class II drugs, fenofibrate and mefenamic acid, with potential applicability to a far wider range of drug substances. en_US
dc.language.iso eng en_US
dc.publisher University of Limerick en_US
dc.subject crystallisation en_US
dc.subject pharmaceutical industry en_US
dc.subject stabilising additives en_US
dc.title Preparation and isolation of drug particles with improved therapeutic response en_US
dc.type info:eu-repo/semantics/doctoralThesis en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.type.supercollection ul_theses_dissertations en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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