Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626177
Title: Volatile formulations for (trans) dermal drug delivery
Author: Henriques Neves Vieira, R. I.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Abstract:
Overcoming the excellent barrier properties of the human skin represents the major challenge of this route of delivery. The Metered dose transdermal spray (MDTS®) is a technology developed by Acrux Ltd (AUS). This passive delivery system has the potential to avoid skin irritation. An informed choice of solvents is one of the strategies to design efficient transdermal formulations. Therefore, it is the aim of this thesis to develop optimal volatile formulations and to investigate the enhancement effects of solvents on drug permeation through the skin. A secondary objective is to evaluate the influence of solvent thermodynamic activity on drug permeation and the transport of solvent through skin on drug delivery. Miscibility, solubility, solvent uptake and residence time studies were conducted as a basis for formulation development. The effects of selected solvents on drug permeation were studied using a flow through diffusion cell design, under clinical dosing conditions of use. The influence of formulation related parameters such as solvent dose, supersaturation, combination of solvents and solvent thermodynamic activity, on the amount of ibuprofen permeated through human epidermis was further studied in vitro. The permeation of octyl salicylate, Propylene glycol and polyethylene glycol 200 was monitored by HPLC/UV, GC/MS and LC/MS, respectively, from selected volatile formulations. From these studies, it was found that ibuprofen permeation from all the residual phases studied was solvent dependent. Superior enhancement was obtained using polyethylene glycol 200 followed by propylene glycol, dipropylene glycol and transcutol®. The excipients in which ibuprofen had higher solubility showed a promotion of drug transport. Furthermore, concentration-dependent effect on ibuprofen permeation from solvents was observed. Significant improvements in the permeation of ibuprofen through human skin were achieved using combinations of solvents. The residual phase composed of polyethylene glycol: octyl salicylate (5:1 and 5:10 % (w/v)) were the best solvent/vehicle for ibuprofen permeation. The findings indicate that drug transport appears to be a function not only of the residual phase excipients, but also of the ultimate fate of the excipients after application. Finally, the reported findings demonstrate the potential of volatile formulations to optimise the efficiency of drug delivery to the skin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.626177  DOI: Not available
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