Title:
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Hydrogels for dermal applications
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This thesis is concerned with the development of hydrogels that adhere to skin and can be
used for topical or transdermal release of active compounds for therapeutic or cosmetic
use.
The suitability of a range of monomers and initiator systems for the production of skin
adhesive hydro gels by photopolymerisation was explored and an approximate order of
monomer reactivity in aqueous solution was determined. Most notably, the increased
reactivity of N-vinyl pyrrolidone within an aqueous system, as compared to its low rate
of polymerisation in organic solvents, was observed. The efficacy of a series of
photoinitiator systems for the preparation of sheet hydro gels was investigated.
Supplementary redox and thermal initiators were also examined. The most successful
initiator system was found to be Irgacure 184, which is commonly used in commercial
moving web production systems that employ photopolymerisation.
The influence of ionic and non-ionic monomers, crosslinking systems, water and glycerol
on the adhesive and dynamic mechanical behaviour of partially hydrated hydrogel
systems was examined. The aim was to manipulate hydrogel behaviour to modify topical
and transdermal delivery capability and investigated the possibility of using monomer
combinations that would influence the release characteristics of gels by modifying their
hydrophobic and ionic nature. The copolymerisation of neutral monomers (N-vinyl
pyrrolidone, N,N-dimethyl acrylamide and N-acryloyl morpholine) with ionic monomers
(2-acrylamido-2-methylpropane sulphonic acid; sodium salt, and the potassium salt of 3-
sulphopropyl acrylate) formed the basis of the study.
Release from fully and partially hydrated hydrogels was studied, using model compounds
and a non-steroidal anti-inflammatory drug, Ibuprofen. Release followed a common 3-
stage kinetic profile that includes an initial burst phase, a secondary phase of
approximate first order release and a final stage of infinitesimally slow release such that
the compound is effectively retained within the hydrogel. Use of partition coefficients,
the pKa of the active and a knowledge of charge-based and polar interactions of polymer
and drug were complementary in interpreting experimental results. In summary, drug
ionisation, hydrogel composition and external release medium characteristics interact to
influence release behaviour. The information generated provides the basis for the optimal
design of hydrogels for specific dermal release applications and some understanding of
the limitations ofthese systems for controlled release applications.
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