Pharmaceutical Technology: Controlled Drug Release, Volume 2

48 CH. 4] STATISTICAL OPTIMIZATION OF A CONTROLLED RELEASE FORMULATION
Table 2—Independent variable levels
Table 3—Optimized responses
Four independent variables were chosen for optimizing flow, compression behaviour and
dissolution kinetics. Table 2 lists these four variables and their experimental ranges (levels). In
order to decrease friability and CI, the percentage of ethylcellulose before the final compression was
decreased.
Table 3 shows the responses to be optimized, among which AUC was considered the most
important. A constant release between 1 and 12 h (passing through 60% dissolved at 8 h) and a
complete dissolution after 14 h were chosen for an optimum profile (AUC=713% h).
As four parameters were studied, three dummy variables X 5 , X 6 and X 7 were included to build a
Hadamard matrix H(8) composed of seven parameters: