Pulsatile Delivery of Fexofenadine Hydrochloride Pulsincap by Box-Behnken Design

Objective: Fexofenadine hydrochloride is a selective peripheral H1-blocker, used for allergy symptoms, such as hay fever and urticaria. Allergic symptoms are aggressive during early morning hours, so a pulsatile delivery system with a lag time of 4-5 hours was formulated and optimized by Box-Behnken design.

Materials and Methods: Pulsincap system using formaldehyde-treated capsules and hydrogel plug. Box-Behnken design was applied for optimization in which three independent variables, X1= Drug: polymer ratio, X2 = Polymer: polymer ratio (Ethylcellulose: HPMC E15) and X3 = Plug weight were selected. Three dependent variables R1 = Percent release of drug after 4 hours, R2 = percent release after 10 hours and R3 = Lag time were selected.

Results: FTIR and DSC studies confirmed compatibility of drug and excipients. The empty formaldehyde-treated capsules were evaluated for physical appearance, solubility, capsule dimensions and formaldehyde content. Hydrogel plugs, powder blend and pulsincap formulations were evaluated for Physico-chemical parameters and all the parameters were within acceptable limits. Contour plots and Response surface plots indicated that as Drug: Polymer ratio (X1) and Plug weight (X3) increased, Lag time increased but% drug release decreased. As Polymer: Polymer ratio (X2) increased, the lag time was at a moderate level. Predicted vs actual responses showed the correlation of 0.786 for% release in 4hrs, 0.9744 for% release in 10hrs and 0.6281 for lag time. Optimized formulation G1 was suggested by design (with criteria 4.5-6hrs lag time, 10-20% release in 4hrs & 60-70% drug release within 10hrs). The optimised formulation was stable.

Conclusion: Pulsincap system of Fexofenadine hydrochloride can be obtained by using retarding polymers like ethyl cellulose, HPMC E15 and formaldehyde cross-linked capsules.