Wong, Suet Mei;
(2005)
Particle formulation for the enhancement of oral bioavailability of poorly water-soluble drugs.
Doctoral thesis (Ph.D.), University College London.
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Abstract
The oral route is the most common route of drug administration for its ease of administration and convenience, which in turn, leads to a relatively high patient compliance. However, problems arise when trying to administer poorly water-soluble drug through the oral route. These drugs usually show a variable and unpredictable bioavailability in vivo with the dissolution rate acting as the rate-limiting step. Increasing the saturation solubility and/or reducing the particle size of these poorly water-soluble drugs are techniques which can be used to increase dissolution rate and subsequently oral bioavailability. The first part of this study was focused on producing novel micro- and nanoparticles of a model hydrophobic drug, which show a better dissolution rate than the control (the unprocessed model drug). Spray drying was one of the techniques used to produce particles. Once suitable spray dried particles were produced, the next step was to spray dry with a hydrophilic surfactant. The aim of using surfactant was to increase the wetting ability of the drug to prevent or reduce aggregation as well as possibly increasing the saturation solubility of the drug. The second technique chosen to form particles was a modified solvent-diffusion method. The particles produced were then characterised using a wide range of pharmaceutical techniques including scanning electron microscopy (SEM), powder X-ray diffraction (PXDR), dynamic contact angle (DCA) and in vitro dissolution testing (USP II apparatus). Once characterisation work was complete, the particles produced were used in in vivo absorption studies in rats. The drug concentration in the plasma was assayed using high performance liquid chromatography (HPLC) and used to obtain pharmacokinetic data including area under the curve (AUC) and bioavailability. The results obtained showed that the particles produced by spray drying had a bioavailability (6.9%) which was significantly higher than those obtained from spray drying without surfactant (3.5%), solvent-diffusion (3.4%) and the control (3.9%). No significant differences were seen in the bioavailability of the control and particles spray dried without surfactant. Although the solvent-diffusion particles had a similar bioavailability to the control, they showed highly variable and unpredictable plasma concentrations.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Particle formulation for the enhancement of oral bioavailability of poorly water-soluble drugs. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10122298 |
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