An Industrial Procedure for Pharmacodynamic Improvement of Metformin HCl via Granulation with Its Paracellular Pathway Enhancer Using Factorial Experimental Design

Abstract

Background

Sorbitan monostearate is a surfactant used in the food industry. It was proved as a penetration enhancer to metformin HCl via a paracellular pathway. It is solid at room temperature and has a low melting point. Therefore, it was selected, as a granulating agent for metformin HCl.

Methods

Multi-level factorial design was applied to determine the optimized formula for industrial processing. The selected formulations were scanned using an electron microscope. Differential scanning calorimetry was used to ascertain the crystalline state of a drug. A modified non-everted sac technique, suggested by the authors, was used to evaluate the in vitro permeation enhancement of the drug. To simulate the emulsification effect of the bile salt, a tween 80 was added to the perfusion solution. As a pharmacodynamic marker, blood glucose levels were measured in diabetic rats.

Results

The results showed that drug permeability increases in the presence of tween 80. Drug permeability from granules increased than that of the pure drug or pure drug with tween 80. The prepared granules decreased blood glucose levels of diabetic rats than the pure drug and drug plus tween 80. There was an excellent correlation between the results of the drug permeation percent in vitro and the dropping of blood glucose level percent in vivo.

Conclusion

Improving the drug permeation and consequently, the drug pharmacodynamic effect in addition to an excellent micromeritics property of the prepared drug granules showed the dual enhancement effect of the suggested industrial procedure. Therefore, we suggest the same industrial procedure for other class III drugs.

Graphical Abstract

Keywords:

• sorbitan monostearate
• class III drugs
• factorial design
• modified non-everted sac

Acknowledgments

We have to express our appreciation to workers and faculty members, the Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, for sharing their pearls of wisdom with us during the course of this research. The abstract of this paper was presented at the 35th Scientific Conference of the Egyptian Pharmaceutical Society, Cairo, Egypt, as a conference talk with interim findings. The authors shared the abstract on the ResearchGate platform: https://www.researchgate.net/publication/340095954_An_industrial_procedure_for_pharmacodynamic_improvement_of_metformin_HCl_via_granulation_with_its_Paracellular_pathway_enhancer

Data Sharing Statement

The raw data supporting the conclusions of this manuscript will be made available by the author Adam A. Al-Shoubki, (E-mail: [email protected]), without undue reservation, to any qualified researcher.

Ethics Statement

All procedures of animal study were approved and regularly controlled by the Animal Ethics Committee of Faculty of Pharmacy Tanta University (No: 2212018) and all experiments were performed in accordance with the guidelines and regulations of this committee. All the procedures were also carried out in full accordance with the ARRIVE guidelines 2020.³⁷

Disclosure

The authors declare no competing interests in this work.