Supercritical fluid coating of flavonoids on excipients enhances drug release and antioxidant activity

• Published in: International journal of pharmaceutics 2023-02, Vol.632, p.122593-122593, Article 122593
• Main Authors: He, Hongling, Huang, Yating, Zhang, Xiubing, Ouyang, Yanting, Pan, Piaopiao, Lan, Yanling, Zhong, Zicheng, Ping, Lu, Lu, Tiejun, Chen, Zhenqiu, Xing, Lei, Li, Qingguo, Qiu, Zhenwen
• Format: Article
• Language: English
• Subjects: Antioxidants; Dihydromyricetin; Drug Liberation; Excipients; Flavonoids; Luteolin; Microscopy, Electron, Scanning; Naringenin; Particle Size; Solubility; Solvents - chemistry; Supercritical anti-solvent fluidized bed
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.122593

[Display omitted] •SAS-FB is used to improve dissolution and bioavailability of poorly soluble drugs.•Drug-loaded flavonoid microparticles of three structures are prepared and compared.•Adhesive morphology depends on carrier/solvent properties and coating conditions.•SAS-FB processed flavonoids dissolves faster with higher antioxidant activity.•SAS-FB is a promising approach for the treatment of natural insoluble products. Supercritical anti-solvent fluidized bed (SAS-FB) technology can be applied to reduce particle size, prevent particle aggregation, and improve the dissolution and bioavailability of poorly soluble drugs. In this work, drug-loaded microparticles of three similar structures, the flavonoids luteolin (LUT), naringenin (NGR), and dihydromyricetin (DMY) were prepared using SAS-FB technology, to explore its effect on the coating of flavonoid particles. Operating temperature, pressure, carrier, solvent, and concentration of drug solution were investigated for their effects on the yield and dissolution of flavonoid particles. The results showed that temperature, pressure, carrier, and drug solution concentration have a large effect on yield. Within the study range, low supercritical CO2 density at higher temperature and lower pressure, a larger surface area carrier, and moderate drug solution concentration led to a higher yield. The effect of the solvent on the yield of flavonoids is a result of multiple factors. Scanning electron microscopy (SEM) images showed that the drug-loaded particles prepared from different carriers and solvents have different precipitations pattern on the carrier surface, and their particle sizes were smaller than unprocessed particles and those prepared by the SAS process. Fluorescence microscopy (FM) results showed that the flavonoids were uniformly coated on the carrier. X-ray powder diffraction (XRPD) results showed that the crystalline morphology of SAS-FB particles remained unchanged after the SAS-FB process, although the diffraction peak intensity decreased. The cumulative dissolution of SAS-FB particles was more than four times faster in the first 5 min than that of the unprocessed flavonoids. The antioxidant activity of SAS-FB processed LUT, NGR and DMY was 1.89-3.78 times, 4.92-10.68 times and 0.99-2.57 times higher than that of the untreated flavonoids, respectively. The approach provides a reference for the application of SAS-FB technology in flavonoids.