Design and Pharmaceutical Evaluation of <i>Piper nigrum</i> Oil Nanoemulsion by Phase Diagram for Topical Analgesic Applications

Abstract

Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.