Formulation and Evaluation of Supramolecular Food-Grade Piperine HP β CD and TPGS Complex: Dissolution, Physicochemical Characterization, Molecular Docking, In Vitro Antioxidant Activity, and Antimicrobial Assessment.

Syed Sarim Imam,Sultan Alshehri,Afzal Hussain,Mohammad A Altamimi,Talal Abdullah Alzahrani

doi:10.3390/molecules25204716

Abstract

The purpose of the present study was to improve the aqueous solubility, dissolution, and antioxidant activity of the water-insoluble drug piperine (PIP). The study was performed by preparing PIP binary inclusion complex (PIP BIC) and piperine ternary inclusion complex (PIP TIC) by different methods. The effect of a hydrophilic auxiliary substance (TPGS) was assessed with addition to PIP and hydroxypropyl beta cyclodextrin (HP β CD) complex. The phase solubility study was performed to evaluate the complexation efficiency and stability constant. The aqueous solubility, dissolution, physicochemical assessment, antioxidant activity, antimicrobial activity, and molecular docking were further evaluated to check the effect of the complexation of PIP. The stability constant (Ks) value was found to be 238 and 461 M−1 for the binary and ternary inclusion complex. The dissolution study results showed a marked enhancement of release in comparison to pure drug. XRD and SEM studies revealed the presence of more agglomerated and amorphous structures of PIP, which confirmed the formation of complexes. The results of DPPH radical scavenging and antimicrobial activity showed a significant (p < 0.05) enhancement in scavenging activity for PIP TIC (microwave irradiation (MI)). The docking studies have revealed that the binding affinity of TPGS at the PIP-HP β CD complex was −5.2 kcal/mol.

Highlights

Piperine (PIP; Figure 1A) is a pungent alkaloid obtained from black pepper (Piper nigrum), long pepper (Piper longum), and other Piper species
It indicates a linear increase in drug solubility as a function of HP β CD concentration, leading to the formation of a first-order complex with respect to HP β CD
In our effort to understand the stable molecular arrangement in the inclusion complexes, we focused on the molecular interactions of PIP and HP β CD with tocopheryl polyethylene glycol succinate (TPGS)

Summary

Introduction

Piperine (PIP; Figure 1A) is a pungent alkaloid obtained from black pepper (Piper nigrum), long pepper (Piper longum), and other Piper species (family Piperaceae). The chemical name is (E,E)-1-piperoylpiperidine and (E,E)-1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentdienyl] piperidine. It is crystalline in nature, having poor water solubility property (40 μg/mL), log P 2.4, and a melting point of 135 ◦ C [1,2]. There are a wide range of pharmacological activities that have been reported for PIP [3,4]. It has an antimicrobial and antiparasitic effect [4]. Due to its poor solubility, its application as a functional ingredient is limited [5]

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Results

Conclusion