Optimization of thermoreversible poloxamer gel system using QbD principle.

The objective of this study was to optimize thermoreversible gel formulations with respect to their gelation temperature and solubilizing capacity, using quality by design (QbD) principles based on design of experiment (DoE). Independent variables, X1, X2 and X3, represent the weight percentages of poloxamer 407 (P407), poloxamer 188 (P188) and the polyethylene glycol 400, respectively (these polymers are either thermoreversible gelling agents or solubilizers). Emodin, a poorly water-soluble compound, was used as a model drug. Fifteen gel formulations were prepared based on the compositions generated by an extreme vertices type of mixture design using a DoE software, in which their gelation temperatures (Y1) and emodin solubility (Y2) were measured. The gelation temperature and emodin solubility were each described adequately using a full cubic model and a quadratic model, respectively. Theoretical and experimental responses showed linearity with R2=0.9943 for the gelation temperature and R2=0.9629 for emodin solubility. The design space was established from the models describing the gelation temperature (test accuracy: 104.5%) and emodin solubility (test accuracy: 96.6%). This study demonstrates successful application of DoE for prediction of gelation temperature and solubility of emodin thermoreversible poloxamer gel (PG). In conclusion, the present DoE approach has led to the establishment of a design space and manufacturing control strategy for gel formulations.