Formulation and Evaluation of Orodispersible Films of Ivabradine Hydrochloride

Abstract

The study set out to construct and optimize oral dispersible films (ODFs) in order to address ivabradine hydrochloride's low oral bioavailability, enhance patient compliance, and guarantee a quick onset of action. Ivabradine is a hyperpolarization- activated cyclic nucleotide-gated (HCN) channel inhibitor that is used to treat heart failure and chronic stable angina. Its high first-pass hepatic metabolism is the cause of its limited oral bioavailability (around 40%). ODFs, a non-invasive, patient-friendly dosage form that dissolves rapidly in the oral cavity and promotes speedy drug absorption through the buccal mucosa, were created to address this problem. Using glycerine as a plasticizer to add flexibility, primogel as a superdisintegrant to speed up disintegration, and Hydroxypropyl methylcellulose (HPMC) as the main film- forming polymer, the films were made by the solvent casting process. To maximize film properties, the study screened several polymer and plasticizer grades and concentrations. To assess the impact of three independent variable polymer concentration HPMC, plasticizer (glycerine), and disintegrant (primogel) on three dependent responses disintegration time (DT) and drug loading (DL), a total of twenty experimental formulations were created using Response Surface Methodology (RSM) with a Central Composite Design (CCD). Physical appearance, thickness, weight homogeneity, folding durability, disintegration time, drug content, and in vitro drug release were all assessed for the manufactured films. The improved formulation showed outstanding mechanical integrity (folding endurance up to 480), substantial drug loading (up to 98%), in vitro drug release (up 95%), and quick disintegration (as low as 32 seconds). The molecular dispersion of Ivabradine within the polymeric matrix was confirmed by analytical methods like Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Scanning Electron Microscopy (SEM). Results of DSC, x-ray diffraction, and SEM also showed a decrease in crystallinity in the ODFs, which indicates improved solubility and bioavailability of the drug in ODFs. This study effectively showed that oral dispersible films are a viable substitute for traditional oral dose forms, particularly for medications with low bioavailability. The created ODFs offer a useful platform for quicker medication administration and better patient compliance, particularly in young, elderly, and dysphagic patients.