Formulation and Topical Safety Evaluation of Zanthoxylum rhetsa Spray Containing Essential Oil from Pericarp: A Phase 1, Double-blind, Non-Randomized, Single-Arm Patch Test Trial

Chureeporn Imphat; Nanthakarn Woottisin

doi:10.26538/tjnpr/v9i10.31

Authors

Chureeporn Imphat Applied Thai Traditional Medicine program, School of Integrative Medicine, Mae Fah Luang University, Muang, Chiang Rai 57100, Thailand
Nanthakarn Woottisin Applied Thai Traditional Medicine program, School of Integrative Medicine, Mae Fah Luang University, Muang, Chiang Rai 57100, Thailand

DOI:

https://doi.org/10.26538/tjnpr/v9i10.31

Keywords:

Zanthoxylum, Essential oils, Formulation, Dermal safety, Phase 1 clinical trial, Irritation, Allergy

Abstract

Our previous study demonstrated that essential oil from the pericarp of Zanthoxylum rhetsa (ESO) has a higher yield and greater potency in inhibiting prostaglandin E2 than essential oil from the fruit. This study aimed to formulate a topical spray containing ESO and to evaluate its safety through patch testing for irritation and allergy. A hydroalcoholic base spray (BS) was formulated and evaluated for appearance, skin feel, pH, viscosity, volume per spray, and evaporation time. Among BS F1–F5, F4 met all criteria and remained stable after six cooling– heating cycles. ESO was incorporated into F4 at 3–9% (v/v) to produce sprays, which passed stability tests. A non-randomized, double-blind, single-arm patch test was conducted in 12 healthy volunteers. Eighteen samples, including BS F4, spray products with 3–9% ESO, ESO alone at 3–9%, and controls, were applied to the upper back for 48 hours and evaluated at 30 minutes and 24 hours post-removal using the International Contact Dermatitis Research Group criteria. All concentrations showed acceptable characteristics; the 9% spray had optimal viscosity and slower evaporation. Clinically (10 completed), five showed no reaction at 30 minutes. One volunteer showed weak positive responses to 8% and 9% ESO and 2% methyl salicylate (score 0.42, slight irritation), and five showed angry back reactions. By 24 hours, all had resolved except one. Therefore, BS F4, sprays with 3–9% ESO, and ESO alone at 3–7% were safe, with the 9% formulation suitable for further clinical evaluation in pain management.

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