Novel fast dissolving freeze dried sublingual baicalin tablets for enhanced hepatoprotective effect: in-vitro characterization, cell viability, and in-vivo evaluation

Pharm Dev Technol. 2024 Apr;29(4):371-382. doi: 10.1080/10837450.2024.2341243. Epub 2024 Apr 13.

Abstract

Baicalin (BG), a natural product, has been used in the prevention and treatment of drug-induced liver injury (DILI); however, its poor solubility and extensive liver metabolism limit its pharmacological use. The aim of the present study was the formulation of fast-dissolving freeze-dried sublingual tablets (FFSTs) to increase BG dissolution, avoid first-pass metabolism, and overcome swallowing difficulties. FFSTs were prepared following a 23 factorial design. The effect of three independent variables namely matrix former, Maltodextrin, concentration (4%, and 6%), binder concentration (2%, and 3%), and binder type (Methocel E5, and Methocel E15) on the FFSTs' in-vitro disintegration time and percentage dissolution was studied along with other tablet characteristics. Differential scanning calorimetry, scanning electron microscopy, in-vitro HepG2 cell viability assay, and in-vivo characterization were also performed. F8 (6% Maltodextrin, 2% Mannitol, 2% Methocel E5), with desirability of 0.852, has been furtherly enhanced using 1%PEG (F10). F10 has achieved an in-vitro disintegration time of 41 secs, and 60.83% in-vitro dissolution after 2 min. Cell viability assay, in-vivo study in rats, and histopathological studies confirmed that pretreatment with F10 has achieved a significant hepatoprotective effect against acetaminophen-induced hepatotoxicity. The outcome of this study demonstrated that FFSTs may present a patient-friendly dosage form against DILI.

Keywords: Baicalin; fast dissolving; freeze drying; hepatoprotective; patient-friendly dosage form; sublingual tablets.

MeSH terms

  • Administration, Sublingual
  • Animals
  • Cell Survival* / drug effects
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Flavonoids* / administration & dosage
  • Flavonoids* / chemistry
  • Flavonoids* / pharmacology
  • Freeze Drying* / methods
  • Hep G2 Cells
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Solubility*
  • Tablets*

Substances

  • Tablets
  • baicalin
  • Flavonoids
  • Protective Agents