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selected to study release properties from medical silicone
elastomer matrix, including a combination of 4 permeation
enhancers as additives and allowing for constraints in the properties
of the material. The D-optimal design included 6 factors and 5
responses describing material properties and release of the drug.
Limitations were set for enhancer and drug concentrations, based
on previous knowledge, in order to retain elastometric properties of
matrix formulations. The total concentration of the excipient and
drug was limited to 15% (w/w ratio) of the silicone matrix; the
maximum drug content was set to 5% and the minimal drug content
to 0.5%, as drug release was one of the most important responses
of the system. With these constraints, the region of experimental
investigation becomes an irregular polyhedron and the D-optimal
design was therefore used. The fi rst experimental object was
screening, in order to investigate the main and interaction effects,
based on 29 experiments. All excipients were found to have
signifi cant effects on diclofenac release and were therefore
included in the optimization, which also allowed the possible
contribution of quadratic terms to the model and was based on 38
experiments. Generally, the enhancers reduced tensile strength
and increased drug release, thus it was necessary to optimize
these 2 responses. Screening and optimization of release and
material properties resulted in the production of 2 optimized
silicone membranes, which were tested for transdermal delivery.
The results confi rmed the validity of the model for the optimized
membranes that were used for further testing for transdermal drug
delivery through heat-separated human skin.
Example
6
Statistical experimental design was applied to evaluate the
infl uence of some process and formulation variables and possible
interactions among such variables, on didanosine release from
directly-compressed matrix tablets based on blends of 2 insoluble
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