Abstract

Kratom (Mitragyna speciosa) extract, containing the analgesic alkaloid mitragynine, is a promising natural therapeutic. However, oral administration is associated with variable bioavailability and potential for abuse. To address these challenges, this study aimed to develop and characterize a transdermal patch for the controlled and sustained delivery of mitragynine. This study systematically evaluated film-forming patches based on natural polymers (agar, pectin, and sodium alginate; Type 3) and a synthetic polymer (polyvinyl alcohol; Type 4). The addition of permeation enhancers was investigated to optimize mitragynine flux across an ex vivo porcine ear skin model. The optimal formulation, a natural polymer film containing 5% w/w eucalyptol as a permeation enhancer, demonstrated superior performance, achieving a steady-state flux (Jss) of 0.60 ± 0.08 μg/cm²/h, a 2.22-fold enhancement over the control patch. This formulation also significantly reduced the permeation lag time from 8 hours to 1 hour. The patch was physically stable, microbiologically clean, and showed no signs of irritation in a rabbit skin screening test. After 6 months of storage at 30°C ± 2°C/75% RH, the lead formulation retained 73.10% ± 1.43% of its initial mitragynine content. These findings indicate the viability of developing a natural polymer-based transdermal patch for the controlled delivery of kratom extract, which is promising for further preclinical investigation as a potential alternative for pain management.

Key words: biocompatible; kratom extract; patch; transdermal delivery; natural analgesic