Mitragynine is a promising candidate for pain relief and opiate replacement but the investigations for drug delivery are lacking. This study aims to investigate the potential of mitragynine to be delivered through the skin with an emphasis on developing and validating a gradient HPLC-UV analytical method to determine mitragynine in the samples collected during in vitro skin permeation studies. The optimised method involves a gradient elution using a C18 column with a mobile phase comprising acetonitrile and 0.1 %v/v of formic acid (0-1 min: 30:70 to 70:30 (v/v) and hold up to 4 min; 4-6 min: return to 30:70 (v/v) and hold up to 10 min) at a flow rate of 1.2 mL/min. This method was validated based on the standards set by the International Council on Harmonisation guidelines. The method showed mitragynine elution at ∼ 4 min with adequate linearity (R2 ≥ 0.999 for concentration ranges of 0.5-10 and 10-175 μg/mL) and acceptable limits of detection and quantification at 0.47 and 1.43 μg/mL, respectively. The analytical performance is robust with excellent precision and accuracy. This method was used to evaluate the in vitro skin permeation of mitragynine (5 %w/v) from simple solvent systems over 48 hr. The results showed a cumulative amount of mitragynine permeated at ∼ 11 μg/cm2 for dimethyl sulfoxide and ∼ 4 μg/cm2 for propylene glycol. The study not only addressed the issues of the currently available HPLC-UV methods that limit the direct application but also affirmed the potential of mitragynine to be delivered through the skin.
The skin functions as a formidable barrier, particularly the stratum corneum, effectively restricting the penetration of most substances, including therapeutic agents. To circumvent this barrier, skin penetration enhancers (SPEs) are frequently employed to transiently increase skin permeability, facilitating drug absorption without causing irritation or damage. Despite advancements in dermal formulation development, a deeper understanding of the fundamental science underpinning drug delivery via SPEs remains essential. This review delivers a critical update on conventional SPEs, exploring their mechanisms in promoting drug permeation across the skin. In addition to offering an overview of percutaneous drug delivery, we examine the prevailing theories on how SPEs enhance drug transport. Furthermore, we address the intricate interplay between SPEs, drugs and the skin, providing valuable insights into how the molecular properties and permeation behaviours of SPEs influence their efficacy. This comprehensive review aims to support the ongoing development of optimised drug delivery systems for dermal applications by elucidating the complexities and challenges involved in using SPEs effectively.