Formulation and Nanotechnology-Based Approaches for Solubility and Bioavailability Enhancement of Zerumbone.

Siddharth S Kesharwani,G Jayarama Bhat

doi:10.3390/medicina56110557

Abstract

About 40–70% of drug molecules in the clinical development pipeline suffer from one of either low aqueous solubility, poor absorption, or extremely low bioavailability. Approximately 75% of the world population relies on traditional therapies and therefore there has been a growing interest in the utilization of natural compounds. Zerumbone is one such natural compound, classified as a sesquiterpenoid that is extracted from the essential volatile oils of rhizomes from Zingiber zerumbet. It possesses strong antitumor, antioxidant, antimicrobial, and anti-inflammatory activity. However, despite promising preclinical studies demonstrating the therapeutic utility of zerumbone, its clinical development has been limited due to its low aqueous solubility, poor absorption, or associated low bioavailability. Multiple reviews demonstrating the pharmacological effects of zerumbone for various diseases have been published. However, to our knowledge, no review demonstrates the various formulation strategies developed to overcome the biopharmaceutical challenges of zerumbone. The purpose of this review is to provide a comprehensive perspective on zerumbone as a molecule for formulation development. A section related to pharmacokinetics, toxicity, and patents of zerumbone is included. This review provides the importance of developing novel formulations of zerumbone to overcome its biopharmaceutical challenges thereby advance its potential in the treatment of various diseases.

Highlights

With the development of novel drug discovery and development methodologies, there has been an increase in the number of new drug candidates in clinical development [1]
The results from this study reported that zerumbone at high concentrations had a genotoxic and cytotoxic effect on Chinese hamster ovary (CHO) cells
The formulation development studies performed are limited to only in-vitro or preliminary in-vivo studies

Summary

Introduction

With the development of novel drug discovery and development methodologies, there has been an increase in the number of new drug candidates in clinical development [1]. It estimated that 40–70% of compounds in clinical drug development suffer from low oral bioavailability due to poor aqueous solubility and absorption [2,3]. Soluble and absorbable drugs pose a significant challenge to the formulation scientists to develop a suitable dosage form that can enhance their solubility and bioavailability [5,6,7,8]. The solubility and bioavailability of a drug can be improved through multiple approaches [9] such as chemical modification, salt formation, amorphization, particle size reduction [10], or through different formulation development strategies [11] such as solid dispersions [12], molecular complexation [13,14,15], lipid-based formulations [16,17,18,19], micelles [20,21], and nanoparticles [22]

Objectives

Methods

Findings

Conclusion