PROCESS OF ORLISTAT-LOADED CHITOSAN NANOPARTICLES USING BOX–BEHNKEN DESIGN – AN EVALUATION STUDY

SRINIVAS MURTHY BR; PRASANNA RAJU YELAVARTHI; DEVANNA N

doi:10.22159/ajpcr.2021.v14i5.41441

Authors

SRINIVAS MURTHY BR Research Scholar, Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University Anantapur, Anantapuramu, Andhra Pradesh, India.
PRASANNA RAJU YELAVARTHI Department of Pharmaceutics Division, Sri Padmavathi School of Pharmacy, Tiruchanoor, Tirupati, Andhra Pradesh, India.
DEVANNA N Department of Chemistry and Director, Oil Technological and Pharmaceutical Research Institute, Jawaharlal Nehru Technological University Anantapur, Anantapuramu, Andhra Pradesh, India.

DOI:

https://doi.org/10.22159/ajpcr.2021.v14i5.41441

Keywords:

Chitosan, Hyperlipidemia, Ionic gelation, Orlistat, Response surface method

Abstract

Objective: High lipophilicity and extensive hepatic metabolism limit oral application of orlistat in obesity treatment. Orlistat-loaded chitosan nanoparticles (CONPs) were optimized by 3-factor 3-level Box–Behnken design (BBD) and surfaced engineered to address limitations.

Methods: CONPs were prepared by ionic gelation method. Amounts of chitosan (X1), sodium tripoly phosphate (X2), and orlistat (X3) were selected as independent factors, whereas % entrapment efficiency (Y1) and % drug release (Y2) were employed as responses in BBD. Three-dimensional response surface plots were run to understand the main interaction and quadratic effects of independent variables. Further optimized formulation was surface engineered by Eudragit L-100 (ECONPs) and characterized by FTIR, DSC, XRD, particle size, zeta potential, and SEM. Entrapment efficiency, release kinetics, stability, and in vitro cell line studies were carried out.

Results: ECONPs were produced with an average size of 534.6 nm, zeta potential of +5.7 mV, EE of 78.62%, and DR of 80.86%. Eudragit coated CONPs anchored the release of orlistat at pH 6.8 desirable for duodenal targeting. Orlistat was released with low, burst, and sustained release manner over 24 h period followed first-order kinetics with Higuchi model with drug content of 84.87% and 78.44% of release. ECONPs possessed lipase inhibition with IC50 value of 8.0 μg/ml and viability against selected cell lines with CTC50 values (26.32–32.21 μg/ml).

Conclusion: BBD was a promising tool in elucidating the insights of formulation variables of CONPs. ECONPs fulfilled the rationale of orlistat release, lipase inhibition, and viability against selected cell lines.

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