Novel Formulations of Amitriptyline: Controlled-Release, Topical, and Nano-Based Delivery Systems

Amitriptyline is a tricyclic antidepressant commonly used to treat depression and, at lower doses, certain chronic pain conditions, including neuropathic pain. However, conventional oral tablets may cause side effects such as sedation and anticholinergic effects, and they are also associated with variable drug exposure and adherence difficulties. To overcome these limitations, researchers have explored controlled-release oral formulations, topical creams and gels, skin-permeation-enhancing systems, and nanoparticle-based formulations. An osmotic controlled-release oral system (OROS) has demonstrated a slower peak concentration with broadly comparable bioavailability to an immediate-release formulation.[8,9] However, topical amitriptyline, alone or combined with ketamine, has shown inconsistent clinical benefits.[3–7] Nano-amitriptyline hydrochloride has demonstrated improved in-vitro dissolution.[11] Further studies are required to establish the stability, pharmacokinetics, safety and clinical efficacy of these novel formulations before they can be considered reliable therapeutic alternatives.