Development and evaluation of p-chlorophenyl benzyl ether-loaded microemulsions for transdermal delivery


  • Kanokwan Singpanna Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Nopparat Nuntharatanapong Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Theerasak Rojanarata Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Panupan Limpachayaporn Department of Chemistry, Faculty of Science, Silpakorn University, Sanam Chandra Palace Campus, Nakhon Pathom 73000, Thailand
  • Prasopchai Patrojanasophon Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Praneet Opanasopit Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand


microemulsions, p-chlorophenyl benzyl ether, phase diagram, skin permeation, transdermal delivery


p-Chlorophenyl benzyl ether (CBE) has been reported to be a new skin brightening agent.  Because of its strong inhibitory effect on tyrosinase and its high safety, CBE was selected as a model antityrosinase compound in this study.  Unfortunately, the poor aqueous solubility of CBE limits its use.  This study aimed to develop a CBE-loaded microemulsion (ME) with enhanced solubility and skin permeation capability for transdermal delivery.  The physicochemical properties, loading efficiency, and skin permeation of CBE-loaded ME were investigated, and results revealed that maximum CBE solubility could be achieved in lemon oil (211.81 ± 15.19 mg/mL).  Thus, lemon oil was selected as the oil phase for the ME formulation. Polysorbate 20 and ethanol at a ratio of 1:1 was employed as a surfactant and co-surfactant mixture (Smix).  A pseudo-ternary phase diagram was constructed to obtain the optimal concentration ranges of oil, Smix, and, water for ME formation.  Here, lemon oil, Smix, and water at a weight ratio of 20:70:10 was formulated with different amounts of CBE (3wt%, 5wt%, and 10wt%). The CBE-loaded ME had a particle size of 152–181 nm and negatively charged surfaces (–16.6 to –14.3 mV).  The percentage loading efficiency of CBE was approximately 70%–100%.  The ME preparation with 5wt% CBE was selected for skin permeation studies, and a 5wt% CBE aqueous suspension (free drug) was used as the control.  The 5wt% CBE-loaded ME exhibited a significantly higher skin permeation flux (32.74 ± 1.36 µg/cm2/h) compared with the 5% CBE suspension (2.35 ± 0.38 µg/cm2/h); specifically, the flux of the CBE-loaded ME was approximately 14-fold greater than that of the free drug.  Therefore, the prepared ME may potentially be used to improve the transdermal delivery of CBE.  However, skin irritation must be further investigated due to the concern on skin irritation of lemon oil and ethanol.


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How to Cite

Singpanna, K. ., Nuntharatanapong, N., Rojanarata, T. ., Limpachayaporn, P. ., Patrojanasophon, P. ., & Opanasopit, P. . (2023). Development and evaluation of p-chlorophenyl benzyl ether-loaded microemulsions for transdermal delivery. Journal of Current Science and Technology, 11(1), 90–99. Retrieved from



Research Article