Computer- aided formulation development - Computer-Aided Applications in Pharmaceutical Technology - page 25

of 11 ANN models suitable for further prediction of phase behavior of
microemulsion-forming systems analyzing only the properties and
contents of the components. The ANN models were developed by
digitalization of phase diagrams of 118 systems, published in the relevant
literature. The inputs were the concentrations of the constituents
(surfactant, cosurfactant, oil, water) and their molecule features (ionic
strength of the water phase, HLB value of the surfactant, density of the
oil, etc.). The outputs confi rmed whether the microemulsion is present or
not for a particular quantitative and qualitative composition. The ANN-
based optimization technique was extended with Neuro-Fuzzy Modeling
(NFM). There have been varied numbers of hidden layers of the MLP
network (from 1 to 5) and up to 100 nodes in neuro-fuzzy systems, by
using neural networks simulator Nets2004 written by the authors. After
the architecture search step, 10 of the best ANNs were selected to become
the expert committee . In addition, a so-called second-order ANN was
employed to combine outputs of the above-mentioned ANNs and to
produce the fi nal decision of the system. The developed expert system
was applied in selection of the surfactant/cosurfactant/water mixtures
(microemulsion preconcentrates) with the high capacity for water
solubilization. The performance of the system was estimated on 77% of
properly classifi ed data records.
Novel investigations pointed to the signifi cance of biocompatible
SMEDDS with the reduced risk for drug precipitation on water dilution,
stabilized with the nonionic surfactants of polyglycolized glyceride types
such as Labrasol ® and Labrafi l ® , Gelucire ® , Cremophor ® , and Plurol ®
groups (Fanun, 2011). Djekic et al., (2011) evaluated the infl uence of the
cosurfactant type, the relative content of the cosurfactant (expressed as a
surfactant-to-cosurfactant mass ratio (K m )), and the oil phase content
(expressed as an oil-to-surfactant/cosurfactant mixture mass ratio (O/
SCoS)) on the water solubilization capacity (W max , %w/w) of Labrasol ®
(PEG-8 caprylic/capric glycerides)/cosurfactant/isopropyl myristate/water,
by application of ANN modeling. The cosurfactants were commercial
nonionic tensides: Plurol ® Isostearique (polyglyceryl-6 isostearate);
Cremophor ® RH40 (PEG-40 hydrogenated castor); Solubilisant gamma ®
2421 ((Octoxynol-12 (and) Polysorbate 20)); and Solubilisant gamma ®
2429 (Octoxynol-12 (and) Polysorbate 20 (and) PEG-40 Hydrogenated
castor oil). The K m values were 4:6, 5:5, and 6:4. The SCoS/O values were
varied from 1:9 to 9:1. The water solubilization limit was detected by
titrating the O/SCoS mixtures with water. The results were used to generate
the inputs and output for ANN training. The inputs were K m and SCoS/O
values. The output was the water solubilization limit (W max , % w/w). The

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