This thesis addresses the development of topical formulations designed to treat atopic dermatitis (AD) using nicotinamide (NA). A rational approach to the development of topical formulations based on the physical and chemical properties of the drug and vehicle components is studied. This approach is an alternative to the model of formulation development where the drug is added into an existing vehicle without optimisation of the formulation in terms of the active delivery to its site of action. The work encompasses preliminary pre-formulation studies, in vitro uptake and permeation studies using a model silicone membrane and pig ear skin. Moreover, the influence of topical formulations containing the model drug on the parameters indicative of skin health is tested in the in vivo studies. The primary objective is to optimise the skin delivery of NA with the use of appropriate excipients. The solvents are chosen on the basis of their physicochemical parameters, namely solubility parameter (δ), mutual miscibility and ability to dissolve the model drug. The performance of rationally developed simple formulations is tested in vitro and compared with prototype formulations containing more complex vehicles. In vitro uptake and permeation studies using silicone are performed to determine the influence of chosen solvents on NA permeation in a membrane which is less complex than skin. In addition NA skin delivery is evaluated with in vitro and in vivo techniques and the relationship between the physicochemical parameters of the solvents used and the drug percutaneous absorption is examined. Finally, the efficacy of prototype NA formulations in improving the skin state in vivo is investigated. The performance of prototype formulations in terms of NA percutaneous absorption is determined with reference to their influence on the skin condition.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:666799 |
| Date | January 2015 |
| Creators | Duszynska-Krupa, A. M. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1468920/ |
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