Microemulsion Gels of Tapentadol Hydrochloride: Statistical Analysis of Pharmacokinetics and Skin Irritation Studies

<b>Background:</b> The present study aimed to overcome the drawbacks of tapentadol through the oral route and to assess the significance of microemulsion gels for transdermal delivery via pharmacokinetic approach. <b>Methods:</b> Microemulsions were prepared via a ternary phase diagram. The optimized microemulsion was converted into gels, and the microemulsion was evaluated for particle size, zeta potential and cumulative <i>in vitro</i> drug release, whereas the gel was characterized for viscosity, spreadability, <i>in vitro</i>, <i>ex vivo</i>, <i>in vivo</i> and skin irritation studies. The prepared ME-gel PKs were tested against MEs, oral solution and plain gel. <b>Results:</b> The PK study revealed that the half-life of the ME gel was 2.2-fold greater than that of the oral solution and 1.65-fold greater than that of the plain gel. The MRT of the ME gel was 6-fold greater than that of the oral solution and 3.3-fold greater than that of the plain gel. The overall mean value of the AUC (0-∞) was 3.16 times greater than that of the oral route. The skin irritation studies found that absence of irritation and damage after application of ME-gel. <b>Conclusion:</b> The PK study revealed that ME-gel was effective in pain management. The level A IVIVC between the <i>in vitro</i> fraction of drug released and the fraction of drug absorbed <i>in vivo</i> was 0.9731.