In vitro characterization of the percutaneous absorption of tramadol into inner ear domestic feline skin using the Franz skin finite dose model

Abstract

Pain, whether it is acute or chronic, can induce stress and reduce overall quality of life for domestic felines. Tramadol, a synthetic opioid that exerts analgesic effects by binding to μ-opioid receptors as well as inhibiting neuronal reuptake of norepinephrine and serotonin, can be used alone or in combination with NSAIDs for the treatment of domestic feline pain. Tramadol can be incorporated into transdermal bases such as PLO or Lipoderm for transdermal delivery. The purpose of this study is to characterize the percutaneous absorption of two tramadol formulations (Tramadol 100 mg/g in PLO and Tramadol 100 mg/g in Lipoderm), when applied to the inner ear of domestic feline skin, In vitro, using the Franz skin finite dose model. A variable finite dose (e.g., 25 μg/cm2) of each formulation was applied to skin sections from two donors and cultured within Franz diffusion cells for 48 hr. Tramadol total absorption, rate of absorption, surface wash, and skin content were quantified using HPLC analysis. Results show that both PLO and Lipoderm were capable of facilitating the percutaneous absorption of tramadol across ex-vivo domestic feline inner ear skin. However, tramadol content within surface wash (3.65%±0.14) was lower for the Lipoderm formulation, which potentially correlates to the higher total absorption (100.40%±3.24) of tramadol when in Lipoderm. Although the rise to peak rate of absorption was approximately 2.5 hr for both formulations, the decline in rate was steadier and more predictable for tramadol in Lipoderm than in PLO. Results of this study can help practitioners and pharmacists predict the in vivo percutaneous absorption of tramadol in domestic felines. The prediction can then guide them in selecting the most favorable transdermal base when prescribing and compounding with tramadol for domestic feline use.