Development of a stable microemulsion - based delivery of amlodipine besylate: a promising approach for topical treatment of anal fissures

Anal fissures (AF) are painful anorectal disorders for which topical calcium-channel blockers (CCBs), such as amlodipine besylate (AMD), are recommended to avoid systemic adverse effects associated with oral therapy. However, the topical use of AMD has been limited by its poor aqueous solubility and chemical instability.This study focused on developing and characterizing a 1% w/w AMD-loaded microemulsion (ME) for topical application. Optimal composition was selected using solubility screening and pseudo-ternary phase diagrams. The lead formulation, M5, demonstrated favorable properties: nanometric scale (size ≈ 34 nm, PDI 0.45), pseudoplastic rheology (viscosity ≈20 Pa·s), and high interfacial stability (ζ - potential +8.7 mV).Franz diffusion cell assays confirmed sustained permeation (steady-state flux ≈14.4 µg·cm-2·min-1), while differential scanning calorimetry evidenced partial plasticization of AMD by the surfactant matrix. The final product was manufactured at pilot scale under GMP guidelines to ensure long-term stability. AMD potency decreased by only 7.7% over 24 months under refrigerated storage. In vitro safety evaluations confirmed a non-irritant profile and low acute toxicity.Compared with other reported topical CCB preparations, this AMD-loaded ME provides superior physicochemical stability, reproducible permeation, and dermal compatibility. These results establish a translational platform for future GMP-scale validation and clinical assessment in AF management.