Development of Bimatoprost-Loaded Nano Spanlastic In-Situ Gel for Ophthalmic Drug Delivery: A Box-Behnken Optimization Approach with In Vitro and Ex Vivo Characterization

PurposeThe present study aimed to develop and optimize a Bimatoprost-loaded spanlastic in-situ gel to enhance precorneal retention, corneal penetration, and therapeutic efficacy while minimizing ocular side effects.MethodsSpanlastic vesicles were prepared using the ethanol injection method and optimized using a 3(3) Box-Behnken design. The optimized formulation was characterized for morphology using transmission electron microscopy (TEM), particle size, entrapment efficiency, and drug-excipient compatibility using FTIR and DSC. The in-situ gel was formulated using 18% poloxamer 407 and evaluated for viscosity, gelling capacity, and drug content. Drug release kinetics, ex vivo corneal permeation through goat cornea, and ocular irritation using the HET-CAM assay were assessed. Sterility, isotonicity, and stability studies were also conducted.ResultsTEM analysis revealed uniform spherical vesicles with a mean particle size of 156.1 +/- 0.82 nm. The vesicles demonstrated high entrapment efficiency and compatibility with excipients. The in-situ gel exhibited favourable viscosity of 610 +/- 1.09 cps, rapid gelation, and high drug content of 99.52 +/- 1.28%. Drug release followed a sustained pattern best described by the Korsmeyer-Peppas model. Ex vivo studies showed enhanced corneal permeation of 89.56% for 8 h, while HET-CAM assays indicated minimal ocular irritation. The optimized formulation (SPs-ISG 18%) was sterile, isotonic, and stable at room temperature.ConclusionThe developed Bimatoprost-loaded spanlastic in-situ gel demonstrates promising potential as a safe and effective ocular delivery system for glaucoma management, offering improved corneal penetration and sustained release.