Since the aim of the study was to analyze the influence of formulation
composition on the in vitro drug release from the laminar
extrudates, an experimental design approach for mixtures was
applied for the planning of the extrusion experiments.
On the basis of the preliminary trials, the component constraints
were set for the percent amount of theophylline
55 6 x1 6 65, lactose 5 6 x2 6 15, and microcrystalline wax
28 6 x3 6 32 to ensure that the experimental composition space
contained feasible formulations with our operating conditions
(e.g. laminar extrudates with a uniform surface and shape) and
to obtain, at the same time, an extrudate with a probable in vitro
sustained drug release. Due to the aim of the research, the response
variables were the in vitro drug release from the prepared extrudates
after 1 h (Y1) and after 8 h (Y2) tested at the conditions
reported in the following Section 2.6.
Table 1 summarizes the design of the optimization study and
acceptance criteria for the drug release.
The experimental plan (shown in Table 2 and Fig. 1), designed
using NEMRODW software (Mathieu et al., 2002), consisted of 13
experimental runs (repeated in doubled experiments) and 6 checkpoints.
To reduce systematic errors experiments were completely
randomized.