Compounded Topical Amitriptyline for Neuropathic Pain: In Vitro Release from Compounding Bases and Potential Correlation with Clinical Efficacy.

Background: Topical amitriptyline has been described as having mixed clinical efficacy for neuropathic pain. A few case reports using higher concentrations of this compound found clinical benefit, but many of these studies did not describe the components used in formulating the amitriptyline preparations.

Objective: To generate reproducible clinical measures of the characteristics of amitriptyline diffusion from selected compounding bases, to support a scientific approach to base selection when compounding this drug for neuropathic pain.

Methods: Amitriptyline hydrochloride (1%, 5%, and 10%) was compounded with 3 proprietary compounding bases: Lipoderm base, Emollient Cream, and Mediflo 30 pluronic lecithin organogel (PLO) gel. In vitro release of the drug from each base and subsequent permeation across artificial human skin were investigated with the Franz diffusion system. Amitriptyline release mechanisms were determined with kinetic models. How quickly and to what extent the drug leaves each base to diffuse through the skin were characterized by determining steady-state flux, cumulative permeation, and lag times.

Results: Release of amitriptyline was significantly higher from the Mediflo PLO gel than from the Lipoderm base or Emollient Cream ( < 0.05). Mean cumulative drug release after 24 h, from the 10% formulation, was 23.9% (standard deviation [SD] 4.1%) for Lipoderm base, 41.8% (SD 3.1%) for Emollient Cream, and 53.2% (SD 7.7%) for Mediflo PLO gel. A high percentage of amitriptyline was retained in all 3 bases. Although amitriptyline release was highest with Mediflo PLO gel, this base resulted in significantly lower cumulative permeation relative to Lipoderm base and Emollient Cream ( < 0.05). There was a strong overall correlation between amitriptyline concentration, lag time, and flux. Higher concentrations were associated with significantly lower lag times and increased flux. The highest lag time and flux were observed for Mediflo PLO gel.

Conclusion: These data indicate that the therapeutic effectiveness of compounded amitriptyline for neuropathic pain depends on its diffusion out of the compounding bases and penetration through the skin.