The aim of this study was to formulate KF fast disintegrating sublingual tablets (FDSLTs). KF has an oral bioavailability of only 50%, as it undergoes first pass metabolism in liver. Sublingual dosage form bypasses the metabolism of KF in liver and offers a fast relieve of asthma also it is not swallowed thus; improve the patient compliance especially for geriatric and pediatric patients, because of swallowing difficulties. To achieve this goal, superdisintegrants and diluents were evaluated for their effect on the disintegration behavior of KF fast disintegrating sublingual tablets. In addition, of enhancing the permeability and bioavailability of selected formulae through comlexation with 2-HP-β-CD. A 24 full factorial design was applied for a screening study in which four factors were used at two levels. Two of these factors, were the type of disintegrants; Ac-di-sol or Explotab, and the concentration of each disintegrant (3% or 5%w/w). 10%w/w Avicel PH101 or PEG6000 was used as binder and the filler was either spray dried lactose or granular mannitol. The weight variation, content uniformity, friability, hardness, disintegration time, and in-vitro dissolution of the prepared formulae were evaluated. The formula F9 containing 5%w/w Ac-di-sol with 10%w/wAvicel PH101and granular mannitol as diluent which has the least disintegration time (about 20 seconds) and the highest dissolution rate was selected as best formula for bioequivalence study. The mean plasma concentration–time courses for KF following the administration of FDSLTs F9 (contains KF without compelxation with 2HP-βCD), Fc9 (contains KF/2HP-βCD complex) and Zaditen® (Novartis-Egypt) tablets in six healthy male volunteers were found to be different following the three treatments, expressed with higher Cmax by about 60% and 90% for both FDSLTs of F9 and Fc9 respectively, and earlier tmax (by 1 h) values for both of FDSLTs F9 and Fc9 compared with Zaditen tablets. The relative bioavailability of Fc9 was 152.45% compared to 130.304% for F9 when Zaditen® tablets were taken as reference standard. The results indicate that KF/2-HP-βCD fast disintegrating sublingual tablets may serve as a successful strategy for enhancing the bioavailability of KF
