Novel delivery approach for ketotifen fumarate: dissofilms formulation using 3² experimental design: in vitro/in vivo evaluation.

Orally dissolving films (dissofilms) have gained increasing popularity and attention due to their ease of administration and avoidance of first pass metabolism. Ketotifen fumarate (KF) bioavailability is reported to be only ~ 50% due to hepatic first-pass metabolism. Aiming to surmount this drawback and improve patients' compliance, a 3(2) full factorial design was applied to formulate KF Orodispersible films, and to investigate the effects and interactions of the concentrations of the novel film former; Lycoat NG73® and the film modifier; maltodextrin (MDX) on the characteristics of the films prepared using solvent casting technique. The dissofilms were thoroughly evaluated regarding their weight uniformity, content uniformity, moisture uptake, in vivo mouth dissolving time (MDT) and their thermal behavior via differential scanning calorimetry. Statistical analysis revealed the significant influence of Lycoat NG73® concentration on percent elongation, percent KF dissolved after 5 min, and in vivo MDT, while MDX concentration had significant effect only on percent elongation. Further, storage of the optimal selected formula (15% Lycoat NG73 and 0% MDX) at 40 °C/75% relative humidity for 12 weeks caused no significant change in appearance, KF content or drug dissolution profile. Pharmacokinetic study revealed that the orally dissolving films showed significantly higher absorption extent than the reference marketed product, while no significant difference was observed for Cmax.