Formulation and Evaluation of Ketotifen Fumarate Fast Disintegrating Sublingual Tablets
Keywords:
Sublingual tablets, Ketotifen Fumarate, 2-HP-βCD, Fast disintegration, BioavailabilityAbstract
The aim of this study was to formulate KF fast disintegrating sublingual tablets (FDSLTs). KF undergoes first pass metabolism in liver, which has oral bioavailability of only 50% of the administrated dose. Sublingual dosage form bypasses the metabolism of KF in liver and offers a fast relieve of asthma. To achieve this goal, superdisintegrants and diluents were evaluated for their effect on the disintegration behavior of KF tablets. Full factorial design (24) was applied for a screening study in which four factors were used at two levels (low and high). The four factors, were the type of disintegrants either Ac-di-sol or Explotab, the concentration of each disintegrant (either 3% or 5% w/w), the binder either Avicel PH101 or PEG6000 and finally the diluent 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. Hydroxy propyle betacyclodextrin (2-HP-β-CD) was used for increasing the absorption of KF tablets formulae. Solid binary system of KF with betacyclodextrin (2HP--β-CD) was prepared in molar ratios of 1:1 of drug to cyclodextrin. The formula F9 containing Ac-di-sol(5%w/w) , Avicel PH101(10%w/w) and granular mannitol as diluent was selected as best formula that has the least disintegration time of 20 seconds and the highest cumulative dissolution percent of 80.28% after the first minute. The relative bioavailability of F9 both with and without the cyclodextrin was compared. Zaditen® tablets were taken as reference standard. The formula F9 showed mean peak plasma concentration Cmax of 25.578±2.65ng/mL, the mean time of peak plasma concentration tmax of 1.167±0.258 h and the AUC (0-∞) of 319.894± 69.13ng.h/mL. However, FC9 that containing the drug in the form of a complex with 2HP-β CD showed Cmax of 30.901±4.963ng/mL, tmax of 1.083±0.186h and AUC (0-∞) of 382.166±55.278ng.h/mL. The results indicate that KF/2-HP-βCD fast disintegrating sublingual tablets may serve as a successful strategy for enhancing the bioavailability of KF drug.
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