Computer- aided formulation development - Computer-Aided Applications in Pharmaceutical Technology - page 21

were prepared according to the orthogonal experimental design. To
optimize the formulation, the infl uences of fi ve factors on characteristics
of the emulsion were evaluated fi rst. Inputs were amounts of gelatin,
insulin, oleic acid, volume ratio of the outer water phase, and agitation
time of the second emulsifi cation process. Outputs were inner droplet
size, viscosity, stability, and pharmacological effect. Based on Analysis of
Variance (ANOVA), it was concluded that the most predominant
contribution of all causal factors was the volume ratio of the outer water
phase. As for the optimization study, the optimum formulation with
respect to pharmacological hypoglycemic effect in rats and stability of
emulsion was estimated using a simultaneous optimization technique, in
which a multivariate spline interpolation (MSI) was incorporated. A two-
factor composite second-order spherical experimental design was used to
select model formulation. The data measured for the model formulations
were analyzed by a computer program (dataNESIA, Yamatake, Tokyo,
Japan). The authors (Onuki et al., 2004) reported that the optimum
formulation had pharmacological activity and stability as high as a
pharmaceutical formulation.
The second emulsifi cation step could be critical for the production of
multiple emulsions. For this reason, Lindenstruth and Müller (2004)
examined the second emulsifi cation step in the formulation of w/o/w
multiple emulsions. Unvaried primary w/o emulsion, with diclofenac
sodium as the active ingredient in the inner water phase, was used during
the investigation. In the second step, a central composite design was used,
and the process parameters pressure and temperature were varied. The
multiple droplet size and the encapsulation rate of totally 10 emulsions
were determined after 1, 3, and 5 homogenization cycles, to investigate
the infl uence of process parameters. For statistical analysis, the Statistica ®
program was used. It was shown that the pressure and temperature, as
process parameters in the second step, infl uenced the size of multiple
droplets in the w/o/w multiple emulsion. Further experiments with
different w/o emulsions resulted in w/o/w multiple emulsions with
different encapsulation rates of diclofenac sodium.
In the work of Wei et al. (2008), formulation optimization of emulsifi ers
for preparing w/o/w multiple emulsions was performed in respect of
stability by using the ANN technique. The emulsifi ers used were sorbitan
monooleate (Span 80) and polysorbate 80 (Tween 80). The stability of
multiple emulsions was expressed by the percentage of reserved emulsion
volume of freshly prepared sample after centrifugation. Individual
properties of multiple emulsions, such as droplet size, phase angle δ,
viscosity of the primary, and the multiple emulsions were also considered.

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