Fast-Disintegrating Nanofibrous Web of Pullulan/ Griseofulvin-Cyclodextrin Inclusion Complexes

Griseofulvin (GSF) is one of the most widely used antifungal suffering from low water solubility and limited bioavailability. Here, cyclodextrin (CD) derivatives of hydroxypropyl-beta-CD (HPfiCD) known for its high-water solubility were used to form inclusion complexes (ICs) with GSF. Here, the molecular modeling study revealed the more efficient complex formation with 1:2 (guest:CD) stoichiometry, so ICs of GSFHPfiCD were prepared using a 1:2 molar ratio (GSF:HPfiCD) and then mixed with pullulan (PULL) to generate nanofibers (NFs) using the electrospinning technique. PULL is a nontoxic watersoluble biopolymer and the ultimate PULL/GSF-HPfiCD-IC NF was obtained with a defect-free fiber morphology having 805 +/- 180 nm average diameter. The self-standing and flexible PULL/ GSF-HPfiCD-IC NF was achieved to be produced with a loading efficiency of -,98% corresponding to -,6.4% (w/w) of drug content. In comparison, the control sample of PULL/GSF NF was formed with a lower loading efficiency value of -,72% which equals to -,4.7% (w/w) of GSF content. Additionally, PULL/GSF-HPfiCD-IC NF provided an enhanced aqueous solubility for GSF compared to PULL/GSF NF so a faster release profile with -,2.5 times higher released amount was obtained due to inclusion complexation between GSF and HPfiCD within the nanofibrous web. On the other hand, both nanofibrous webs rapidly disintegrated (-,2 s) in the artificial saliva medium that mimics the oral cavity environment. Briefly, PULL/GSF-HPfiCD-IC NF can be a promising dosage formulation as a fast-disintegrating delivery system for antifungal oral administration owing to the improved of GSF.