Development and optimization of Benjakul microemulsion formulations for enhancing topical anti-inflammatory effect and delivery
Pranporn Kuropakornpong1, Arunporn Itharat2, Buncha Ooraikul3, Raimar Loebenberg4, Neal M Davies4
1 Graduate School, Faculty of Medicine, Thammasat University, 12120, Pathumthani, Thailand
2 Department of Applied Thai Traditional Medicine, Faculty of Medicine; Center of Excellence on Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, 12120, Pathumthani, Thailand
3 Department of Agricultural Food and Nutritional Science, Faculty of Agricultural Life and Environmental Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
4 Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group-Rexall Centre for Pharmacy & Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada
Department of Applied Thai Traditional Medicine, Faculty of Medicine; Center of Excellence on Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, 12120, Pathumthani
Source of Support: None, Conflict of Interest: None
Background and purpose: Benjakul (BJK) is a combination of five botanical herbal constituents widely used in Thai traditional medicine as an anti-inflammatory remedy. This study aimed to develop a novel topical microemulsion containing BJK for clinical use.
Experimental approach: The microemulsions were produced by a phase inversion temperature (PIT) methodology. Physicochemical properties and stability were evaluated to determine an optimal formula. The stable BJK-loaded microemulsion formulas were then subjected to in vitro studies for their anti-inflammatory activity, skin cell toxicity, drug permeation, and stability.
Finding/Results: Two novel formulations containing isopropyl myristate (ME1-BJK and ME2-BJK) passed the compendial stability test. BJK constituents were completely dissolved in the oil phase and incorporated into the microemulsion base Transcutol® and Labrasol® avoiding the use of alcohol, both microemulsion formulations demonstrated high anti-inflammatory activity with IC50 values of 3.41 ± 0.36 and 3.95 ± 1.73 μg/mL, respectively. However, dissolution of ME1-BJK showed a superior release profile through both lipophilic and hydrophilic membranes with the highest accumulated amount at 4 h of 25.13% and 38.06%, respectively. All tested formulations of BJK extract demonstrated no apparent skin cell toxicity at concentrations up to 50 μg/mL. After six-month storage under accelerated conditions, there were no significant changes in anti-inflammatory activity.
Conclusions and implications: A novel and stable BJK-loaded microemulsion formulation was successfully developed with excellent release and stability properties. Further clinical research to evaluate pain reduction, edema, and skin irritation using this formulation in animal models is ongoing.