QBD APPROACH FOR THE DEVELOPMENT OF CAPSAICIN-LOADED GLYCYRRHETINIC ACID CONJUGATED STEARIC ACID GRAFTED CHITOSAN POLYMERIC MICELLES FOR ACTIVE HEPATIC TARGETING

MAYURI K.; SUNITHA S.

doi:10.22159/ijap.2023v15i4.47770

Authors

MAYURI K. Department of Pharmaceutics, Gitam School of Pharmacy, GITAM Deemed to be University, Hyderabad, Telangana-502329, India https://orcid.org/0000-0002-3235-4175
SUNITHA S. Department of Pharmaceutics, Gitam School of Pharmacy, GITAM Deemed to be University, Hyderabad, Telangana-502329, India

DOI:

https://doi.org/10.22159/ijap.2023v15i4.47770

Keywords:

Capsaicin, Chitosan, Stearic acid, Glycyrrhetinic acid, 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, low bioavailability, and less target-specific release. Hence, the present study aimed to synthesize glycyrrhetinic acid conjugated stearic acid grafted chitosan (GA-CS-g-SA) and prepare CAP-loaded GA-CS-g-SA micelles.

Methods: Quality by design (QbD) approach in coordination with "Box-Behnken Designs (BBD)" was used to optimize the process parameters. GA-CS-g-SA was synthesized and characterized for its physic-chemical.

Results: The "Proton Nuclear Magnetic Resonance (¹H NMR)" spectrum depicted a strong signal at d=1.0 ppm and endorsed to-CH₂ group of SA and d=3.5-3.65 ppm depicting GA, which confirms the formation of GA-CS-g-SA. Critical micellar concentration (CMC) was found to be 13.45±1.72 µg/ml and amino groups substitute degree (SD %) was 10.12%±1.09%, indicating successful linkage of GA and SA on CS. The prominent peaks of CAP (0.9 and 1.31 ppm) in ¹H NMR spectra disappeared, indicating drug loading in the micellar core. Micelle's normal particle range was 167.54 nm, and encapsulation efficiency was 67.85%. The CAP-GA-CS-g-SA was found to be biocompatible following the hemolysis test. In vitro release pattern showed 78.68±3.12% in 24h, indicating the slower release of CAP from micelle, whereas 99.48±2.56% was released from non-micellar formulations in 6 h. CAP release from drug-loaded micelles showed a biphasic model with an early burst release in four hours, following a slower and sustained release pattern till 24h.

Conclusion: CAP-GA-CS-g-SA micelle is a hopeful advancement to progress bioavailability and controlled release of highly hydrophobic CAP. Further in vivo studies would be evident for targeting hepatocytes and treating AH using CAP-GA-CS-g-SA.

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