# Design and Pharmaceutical Evaluation of Piper nigrum Oil Nanoemulsion by Phase Diagram for Topical Analgesic Applications

## TL;DR

Researchers developed a stable nanoemulsion using black pepper oil for potential use as a natural topical pain reliever.

## Contribution

The study introduces a stable nanoemulsion formulation of Piper nigrum essential oil for topical analgesic applications.

## Key findings

- A nanoemulsion with 2.7% P. nigrum essential oil showed optimal stability and physical properties.
- The optimized formulation ST42 had a zeta potential of -8.12 ± 2.0 mV, indicating low irritation potential.
- The nanoemulsion passed pharmaceutical quality tests, suggesting potential as a natural pain reliever.

## Abstract

Plant-based pain-relieving formulations have garnered attention in drug discovery, particularly those with a traditional background, often considered essential remedies for communities that rely on plant-based therapies for pain relief.

This study aimed to develop and evaluate a semisolid nanoemulsion using Piper nigrum L. (black pepper) fruit essential oil, known for its analgesic properties, as the active ingredient.

A topical nanoemulsion was prepared under standard conditions using black pepper essential oil, emulsifiers, and excipients. Various combinations of Span 80 and Tween 80 were screened to achieve the desired hydrophilic-lipophilic balance (HLB) value. Among the several formulations prepared, a nanoemulsion sample was selected for detailed analytical and pharmaceutical evaluations. Gas chromatography with flame ionization detection (GC/FID) was used to identify and quantify major chemical constituents of the essential oil and the formulated nanoemulsion.

An optimized combination of Span 80 and Tween 80, with an HLB of 11, contributed significantly to the physical stability of the formulations. A concentration of 2.7% P. nigrum essential oil in the nanoemulsion containing 3793.33 ± 222.75 µg/mL of caryophyllene, the major bioactive monoterpene, rendered a stable and acceptable nanoemulsion product. The nanoemulsion formulation ST42 was declared to have a viscosity of 1.8 MPa.s, ST mix (Span 80/Tween 80, 1.5:2.5), and a ratio of surfactant/essential oil (40:60), demonstrated optimal consistency and physical stability. The zeta potential (Z) of the optimized formulation ST42 was found to be close to neutral (-8.12 ± 2.0 mV), minimizing potential tissue irritation. The nanoemulsion was ultimately validated using a modified homogenization technique to improve droplet size, stability, and rheological characteristics.

The formulated black pepper nanoemulsion successfully passed key pharmaceutical quality tests, indicating its potential as a natural topical pain-relieving agent. Further in vivo studies and subsequent clinical trials may lead to the development of a plant-based product for managing neuropathic pain.