Design and optimization of silymarin loaded in lyophilized fast melt tablets to attenuate lung toxicity induced via HgCl₂ in rats

Abstract

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 3² factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q₁₀). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q₁₀ of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl₂ in a manner comparable to free SM at the same dosage.

Keywords:

• Silymarin
• fast melt tablets
• lyophilization
• lung toxicity
• miRNA 133a
• miRNA155
• COX-2

Institutional review board statement

The in-vivo trials were carried out based on the guidelines established by the Animal Care and use Committee faculty of Applied Medical Science, October 6 University, Giza, Egypt, Approval no: 20210502, Date: 2/05/2021.

Informed consent statement

All Authors agree that the contents of the manuscript are confidential and will not be copyrighted, submitted, or published elsewhere (including the Internet), in any language, while acceptance by the Journal is under consideration.

Author contributions

Equal contribution between authors in conducting the experiments, writing the manuscript, reviewing, and editing.

Disclosure statement

The authors declare no competing interests.

Data availability statement

All relevant data are within the manuscript and any other additional materials are available upon request.