<![CDATA[Transdermal drug delivery has emerged as an effective alternative to conventional analgesic administration, offering controlled release, improved bioavailability, and reduced systemic side effects. This literature review evaluates the analgesic potential of Piper nigrum L. fructus ethanol extract formulated into transdermal patches using various penetration enhancers. A total of ten peer-reviewed studies published between 2015 and 2025 were examined to identify trends in formulation strategies, enhancer mechanisms, and analgesic outcomes in animal models. The findings reveal that Piper nigrum extract demonstrates consistent analgesic activity through modulation of nociceptive pathways involving piperine, its primary bioactive constituent. The incorporation of enhancers such as oleic acid, propylene glycol, menthol, and DMSO significantly improves transdermal permeation, leading to higher therapeutic efficacy compared to formulations without enhancers. Most studies report increased inhibition of the writhing response, prolonged latency in hot-plate tests, and enhanced anti-inflammatory activity. However, variations in enhancer concentration, polymer composition, and evaluation methods contribute to heterogeneity in outcomes. Despite these differences, current evidence supports the potential of Piper nigrum-based transdermal patches as a promising analgesic modality. Further standardized in vivo studies and clinical investigations are required to validate optimal enhancer combinations, safety profiles, and dosage parameters.]]>
