Development and evaluation of novel famotidine-loaded fast dissolving sublingual film using the quality-by-design approach

Abstract

The present study deals with the development and evaluation of a novel famotidine (FMD) loaded fast-dissolving sublingual film based on quality-by-design approach using a solvent casting technique. Initially, quality target product profile (QTPP) was set to build quality in patient-centric products. The risk assessment and risk management were performed using Ishikawa diagram and failure mode effect analysis (FMEA). A central composite design (CCD) was employed in order to assess the effect of the formulation variables such as HPMC K-15 and PEG-400 on their responses such as content uniformity, folding endurance, and thickness. The developed optimized sublingual film was characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) for its intermolecular interactions. The morphology of the optimized film was studied by scanning electron microscopy (SEM) in which the drug particles appeared spherical. The developed film showed stability for 3 months according to the International Conference on Harmonization (ICH) Q1A (R2) guidelines. A dissolution study showed enhanced dissolution for the optimized sublingual film as compared to the buccal and oral film. The permeation study of the optimized film showed the highest permeation within 30 min. In vivo study using rabbit as model animal exhibited the improved bioavailability of the drug i.e. 2.05 folds. The drug reached systemic circulation within 15 min to improve bioavailability significantly. Thus, the fast dissolving sublingual film containing FMD potentially overcomes the biopharmaceutical challenges and can be a better alternative system for the administration of FMD for the treatment of peptic ulcers.