SCREENING AND CHARACTERIZATION OF FAVIPIRAVIR-LOADED NANOSTRUCTURED LIPID CARRIER FORMULATIONS BY USING A 26-2 FRACTIONAL FACTORIAL DESIGN

MAXIUS GUNAWAN; DAVID G. FERNIG; VEERAKIET BOONKANOKWONG

doi:10.22159/ijap.2025v17i4.53891

Authors

MAXIUS GUNAWAN Graduate Program of Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand https://orcid.org/0000-0002-6622-4061
DAVID G. FERNIG Department of Biochemistry, Systems and Cell Biology, Institute of Systems, Molecular and Integrated Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom https://orcid.org/0000-0003-4875-4293
VEERAKIET BOONKANOKWONG Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand https://orcid.org/0000-0002-6231-5935

DOI:

https://doi.org/10.22159/ijap.2025v17i4.53891

Keywords:

Favipiravir, Nanostructured lipid carriers, Quality by design, Screening formulation

Abstract

Objective: Favipiravir (FVP), an RNA-dependent RNA polymerase inhibitor with low solubility and bioavailability, was encapsulated and optimized into Nanostructured Lipid Carriers (NLC) to improve solubility and control its release profile.

Methods: The FVP-NLC formulation was screened using a 2^6-2fractional factorial design with 6 critical parameters at 2 levels, which were solid lipid combination (Glyceryl Monostearate (GMS) and combination with Cetyl Alcohol (CA) (1:1)), liquid lipid combination (Medium-Chain Triglycerides (MCT) oils and combination with Ethyl Oleate (EO) (1:1)), solid to liquid lipid ratio (70:30 to 90:10), concentrations of total lipid (2-5% w/v), surfactant (Tween^® 80, 2-5% w/v), and co-surfactant (Labrasol^®, 1-2% w/v). Sixteen formulas were obtained. FVP-NLC was fabricated using high-shear homogenization (12,000 rpm for 10 min), tandem ultrasonication (amplitude 40% for 5 min), followed by characterization of particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimum formula was further evaluated for in vitro release and kinetics study, as well as short-term stability study under refrigerator (5±3 °C), room temperature (25±2 °C, 60±5% RH), and climatic chamber (40±2 °C, 75±5% RH) for 15 d.

Results: The major contributions of parameters were total lipid (32%), co-surfactant concentration (30%), and solid lipid combination (15%). The best formulation was F3 with total lipid 2% w/v, co-surfactant 2% w/v, and GMS showing small particle size (124.1±1.8 nm), polydispersity index (0.1387±0.0043), and zeta potential (-39.06±2.00 mV), with high entrapment efficiency (85.97±0.06% w/v). In vitro release from F3 demonstrated controlled release with diffusion mechanisms for up to 24 h at pH 7.4, following Korsmeyer-Peppas kinetics (R² = 0.9171, n = 0.231). In addition, the short-term stability study revealed that F3 has consistent physicochemical properties for 15 d in all conditions.

Conclusion: The 2^6-2fractional factorial design has been successfully utilized in screening FVP-NLC formulation to incorporate FVP into the NLC matrix system.

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