Orally fast-dissolving drug delivery systems for pediatrics: Nanofibrous oral strips from isoniazid/cyclodextrin inclusion complexes

Isoniazid (INH) is an essential antibiotic for tuberculosis that suffers from low water-solubility and limited bioavailability due to its crystalline form. Generation of inclusion complex nanofibrous film of isoniazid with highly water soluble cyclodextrin derivates can enable the development of a new oral delivery system with fastdisintegrating feature. In this study, the inclusion complex (IC) of INH and hydroxypropyl-beta cyclodextrin (HPI3CyD) were fabricated into nanofibrous film through electrospinning technique. Here, HPI3CyD was used for both encapsulation of INH and electrospinning of free-standing nanofibrous films. Electrospinning of INH/ HPI3CyD-IC system resulted into uniform and homogenous fiber morphology having -400 nm mean diameter. The ultimate INH/HPI3CyD-IC nanofibers were obtained with a -100% of loading efficiency (-8% (w/w) of INH content) without loss of drug content during whole process. Due to inclusion complexation, the electrospinning and amorphization of INH within the INH/HPI3CyD-IC nanofibrous film was achieved without the use of any organic solvents or toxic agents. The amorphous state of INH and the unique properties of nanofibrous matrix ensured faster and enhanced release profile for INH molecules compared to its pristine powder form. Additionally, INH/HPI3CyD-IC nanofibrous film presented a quite fast-disintegration profile in the saliva simulation (-2s). Overall, this approach revealed a promising administration of orally fast-dissolving drug delivery system, especially for pediatric patients.