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Title: Investigation of the formulation, characteristics and performance of polymeric drug carrier particles intended for oral administration
Author: Bohr, A.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Micro- and nanoparticles are being widely investigated for pharmaceutical purposes and are beginning to see application in clinical practice. There are numerous techniques to produce such therapeutic particles, including emulsion-based techniques and spray drying, each with their advantages. Electrospraying provides an alternative technique for preparing drug-loaded particles in the micro-scale with a good control of important particle characteristics, such as size and shape. In this work, electrospraying was used to investigate its potential for producing microparticles intended for oral administration of low solubility drugs. Different processing parameters including flow rate, solute concentration, drug loading and type of solvent and their influence on particle characteristics and drug release were studied using Celecoxib as a model drug and poly(lactic-co-glycolic acid) as a carrier material. The role of solvent mixtures were studied in detail with respect to particle characteristics and drug release kinetics and additional studies were performed for microparticles prepared with Celecoxib and the polymer Hypromellose Acetate Succinate. The electrosprayed particles were then compared with particles prepared with spray drying using similar experimental conditions and their performance was tested. Electrosprayed microparticles were prepared with diameters between 2-8 m and a near-monodisperse size distribution was obtained in most cases. The morphology of the particles ranged from smooth and spherical to rough and non-spherical depending on parameters used and were mainly attributed the evaporation rate and solubility of solute in the solvents. They are different from the spray dried particles which were all smooth, spherical and with a broader size distribution. Electrosprayed particles also showed more porosity and a different drug distribution compared with spray dried particles. The drug molecules were in an amorphous form in particles prepared using both techniques and remained stable after 8 months of storage. Drug release studies showed differences in release profiles depending on the parametric values. The drug release rates were directly related to the particle size, morphology, porosity and drug distribution observed and hence influenced by the studied process parameters. Spray dried particles generally had a slower drug release rate compared with electrosprayed particles attributed to differences in the particles characteristics observed. The results indicated that electrospraying is an attractive technique for producing drug loaded microparticles that can be tailored towards an intended drug delivery application. Compared with the more conventional spray drying process it provides better control of particle characteristics and demonstrated its suitability for preparing particle-based solid dispersion formulations in which the drug is molecularly dispersed and is released in a sustained manner to potentially improve oral bioavailability of low solubility drugs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available