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Title: The development and evaluation of a hydrogel drug delivery system for dithranol
Author: Priprem, Aroonsri
ISNI:       0000 0001 3501 9084
Awarding Body: Robert Gordon Institute of Technology
Current Institution: Robert Gordon University
Date of Award: 1991
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Dithranol is widely used in the treatment of psoriasis, but it has the drawbacks of instability, staining of skin and clothes, and irritation, especially of non-involved skin. A polyurethaneurea hydrogel in sheet form has been used to investigate the possibility of developing a drug delivery system that would confine dithranol to the psoriatic plaque, whilst also providing appropriate stability and drug delivery rates. Analytical methods were developed and evaluated, to ensure that dithranol stability could be monitored and release rates measured. A high-performance liquid chromatography (HPLC) method enabled the assay of dithranol, danthrone and dimer at concentrations appropriate for stability studies and longer-time release experiments. A more sensitive fluorimetric method enabled assay of the dithranol in the low concentrations occurring in the early stages of release experiments. Hydrogels were loaded using a dithranol solution. The blend of solvents for the loading solution were selected to optimize dithranol solubility and hydrogel swelling, and to minimise oxidation of dithranol. Storage conditions for the loading films were also optimized until a zero order half-life of 30 days for the loaded film was obtained. In vitro release studies indicated that the process was slower and less extensive into aqueous media than into non-aqueous media. Stratum corneum, however, acts as a rate-limiting membrane so that the release rate became independent of receptor medium hydrophobicity. A rate constant of dithranol release from hydrogel through stratum corneum of 0.2 ?g/cm2/hr was obtained. The hydrogel was evaluated on 5 normal and 8 psoriatic patients. Clinical response was measured by scoring scaliness, thickness, erythema and staining. Detailed time course evaluation on two psoriatic patients indicated that there was a lag time of 7 hours after application before the first clinical response was obtained. Comparative studies on 5 normal volunteers indicated that there was an approximate bioequivalence between the hydrogel and 0.1% Dithrocream. This was confirmed with 6 psoriatic patients which also showed that both are more effective than occlusion alone or blank hydrogel. From the data obtained, some suggestions about the possible effective concentration - and the site and mechanism - of action of dithranol in psoriasis are discussed.
Supervisor: Winfield, A. J. ; Moody, R. R. ; Richards, R. M. E. Sponsor: British Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Dithranol ; Psoriasis ; Hydrogels ; Drug delivery