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

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.

Graphical Abstract

Keywords:

• Baicalin
• hepatoprotective
• freeze drying
• sublingual tablets
• fast dissolving
• patient-friendly dosage form

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

F.N.A: Data curation; Investigation; Methodology; Formal analysis; Writing-original draft, R.A.S: Investigation; Methodology; Formal analysis; Validation; Writing-original draft, S.A.F: Investigation; Methodology; review & editing, R.M.E: Investigation; Methodology; review & editing, SEA: Writing- review & editing; Resources; Software, Y.M.A: Investigation; Methodology, N.S.A: Conceptualization; Validation; Project administration; Resources; Supervision; review & editing

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.