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Title: Polymer-surfactant stabilised drug nanoparticles
Author: Tirop, Lucy
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2012
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Wet bead milling, in which the drug is milled in presence of stabilisers such as polymers and surfactants, has enabled the formulation of poorly water-soluble drugs as nanoparticles, with five products having reached the market. During the milling process, the polymer and/or surfactant adsorbs onto the freshly cleaved drug surfaces to provide ionic or steric stabilisation. Despite the success of wet bead milling, mastery of the mechanism behind nanoparticle stabilization is still lacking. To investigate whether any relationship exists between drug, stabiliser and stabilisation, eight structurally different poorly water-soluble drugs were milled in presence of thirteen different pharmaceutically acceptable stabilisers and the resultant particle size determined by photon correlation spectroscopy. Nanoparticles of the BCS class II drugy griseofulvin, could only be produced in presence of anionic stabilisers namely sodium dodecyl sulphate, aerosol-OT or hydroxypropylmethylcellulose acetate succinate. Surfactant adsorption isotherms obtained indirectly by measuring their depletion from solution revealed a maximum surfactant adsorption of ~ 2.2 mg/m2 on the griseofulvin nanoparticle surfaces. The use of ionic surfactants/polymers in oral formulations is however sub-optimal. Consequently, polymer-surfactant co-stabilisation, used to take advantage of the synergy between ionic and non-ionic stabilisers, was investigated by the inclusion of the non-ionic polymer hydroxypropylmethylcellulose (HPMC) into the anionic surfactant-drug slurry prior to milling. The effect of varying HPMC molecular weight and concentration on griseofulvin nanoparticle production was established. Polymer adsorption isotherms were obtained directly via small angle neutron scattering.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available