QBD APPROACH FOR THE DEVELOPMENT OF CAPSAICIN-LOADED STEARIC ACID-GRAFTED CHITOSAN POLYMERIC MICELLES

Abstract

Objective: Capsaicin (CAP) is a naturally occurring alkaloid forecasted in the treatment of Alcoholic Hepatitis (AH), but least studied due to its hydrophobicity and low bioavailability. Hence, the present study aimed to optimize the parameters for the synthesis of stearic acid grafted chitosan (CS-g-SA) copolymer and preparation of CAP-loaded CS-g-SA micelles. Methods: Quality by design (QbD) approach in coordination with “Central composite designs (CCD) and Box–Behnken designs (BBD)” was used to optimize the process parameters. Results: CS-g-SA was synthesized at 80 °C, 480 min, and 946 rpm, at these optimized conditions, the average particle size and practical yield were found to be 134.70 nm and 85.69%, respectively. Proton Nuclear Magnetic Resonance (1H NMR) spectra depicted a sharp signal at d=1.0 ppm endorsing to -CH2 group of SA and confirming the formation of CS-g-SA copolymer. Critical micellar concentration (CMC) and amino groups substitute degree (SD %) were found to be 30.3±1.51µg/ml and 21.3±0.58%, respectively. The distinguished peaks of CAP (0.9 and 1.31 ppm) in 1H NMR spectra disappeared, indicating drug loading in the micellar core. Micelles had an average particle size of 163.15 nm and an encapsulation efficiency of 68.45%. The CAP-CS-g-SA was found to be biocompatible in accordance with the hemolysis test. The in vitro release pattern showed 86.78 % in 24 h, indicating the slower release of CAP from micelle, whereas 99.48% CAP was released from non-micellar formulations in 6 h. Conclusion: CAP-CS-g-SA micelle is a promising approach to improve the bioavailability and controlled release of extremely hydrophobic CAP and further in vivo studies would be evident for the treatment of AH using CAP-CS-g-SA.