Topical NSAIDs for acute local pain relief: in vitro characterization of drug delivery profiles into and through human skin

Abstract

Objective: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) relates not only to the individual NSAID used but also to differences in formulation design. The aim of this study was to investigate the fundamental differences in ibuprofen and diclofenac drug delivery vehicles, specifically gels and plasters, compared to a recently launched 200 mg ibuprofen medicated plaster and characterize the resulting dermatologic-pharmacokinetic profiles into and through ex vivo human skin layers. Methods: In vitro skin permeation testing over 24 h and sacrificial timepoint penetration experiments (at 1, 4, 8, 12, and 24 h) were conducted using an automated flow-through diffusion cell system. The amount of drug delivered to the epidermis, dermis, and receptor solution (representing deeper tissue) was determined by liquid chromatography-tandem mass spectrometry. Skin protein binding of ibuprofen and diclofenac was investigated by spiking skin homogenate with increasing concentrations of each drug and determining the fraction unbound. Results: Differences were observed in the amount of drug recovered at sacrificial timepoints and rate at which drug was delivered to the target site between plaster and gel formulations of ibuprofen and diclofenac and between plaster formulations of the same drug (ibuprofen). While the amount of drug quantified at sacrificial timepoints did not necessarily determine in vivo flux rates, differences in drug distribution within the skin layers indicated where drug reservoirs were formed. Conclusions: These findings highlight the importance of intelligent formulation design in determining NSAID delivery through skin layers. Further work is required to quantify drug delivery into deeper tissues and the resultant local anti-inflammatory effects.

Testing Topical Products Specifically to Reduce Inflammatory Pain from Gout: Transdermal NSAID Delivery and Monosodium Urate Solubility

“…The observed faster permeability of ibuprofen agrees with previously observed results. 7 , 8 In a recent paper by Pradal, 7 it is suggested that the higher potency of diclofenac would result in a significantly higher values of “modified index of anti-inflammatory activity” for the diclofenac products in-spite of the lower permeation rates versus ibuprofen (around 10 fold increase for diclofenac). However, another recent paper by Wade et al 14 compared 1% diclofenac gel with 5% ibuprofen gel and 5% ibuprofen/3% menthol gel in a clinical trial.…”

“…These include concentration of drug, the drug properties, specific salt used and the formulation. 7 , 8 However, most topical NSAID drug delivery results in lower systemic levels of drug when compared to recommended oral doses. 9 , 10 Therefore, higher permeation is generally desired to maximise the anti-inflammatory effect of topically applied NSAIDs.…”

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

“…Opting for NSAIDs in cream or gel formulation stands out as a preferred approach for managing OA, especially among the elderly. While these topicals may exhibit a slower absorption rate, their pharmacological activity is comparable to oral alternatives [157,158]. Their use is recommended by the main international guidelines for knee and hand OA treatment according to superior safety profile.…”