Development and Optimization of Carteolol Loaded Carboxymethyl Tamarind Kernel Polysaccharide Nanoparticles for Ophthalmic Delivery: Box-Behnken Design, In Vitro, Ex Vivo Assessment

In the present study, three level and two factor Box-Behnken statistical experimental design was used to optimize the carteolol loaded carboxymethyl tamarind kernel polysaccharide nanoparticles (CMKP) formulation for ocular delivery system. The effects of three independent parameters like polymer concentration, calcium chloride (CaCl2) concentration (crosslinking agent) and sonication time were studied on dependent variables like particle size and entrapment efficiency. The fitted mathematical model allowed us to plot response surfaces curves and to determine optimal preparation conditions. Results clearly indicated that polymer concentration and crosslinking agent were the main factor influencing particle size and entrapment efficiency. Optimization was done by point prediction of software and the concentrations which were found to be optimum i.e., carboxymethyl tamarind kernel polysaccharide (0.15% w/v), CaCl2 (0.20% w/v), and sonication time (30 min) with 223.66 +/- 3.56 nm particle size and 38.32 +/- 2.14% entrapment efficiency. The nanoparticles were characterized for in vitro release and transcorneal permeation study which revealed sustained release and significant permeation (P = 0.0058) as compared to pure drug solution. The nanoparticles were also characterized for bioadhesion, irritation study (Hen Egg Test-Chorioallantoic Membrane, HET-CAM), confocal microscopy and histopathology study and the results showed that the formulation could be prepared successfully promising their use in ocular delivery.