Formulation, Characterization, and Optimization of a Topical Gel Containing Tranexamic Acid to Prevent Superficial Bleeding: In Vivo and In Vitro Evaluations.

Abstract

Tranexamic acid (TXA) is used systemically to stop bleeding, but it can lead to thromboembolism. Trials have revealed the efficacy of topical TXA on local hemorrhages. However, there is a need for an efficient delivery system that can keep the drug at the site of action. To develop a gel containing TXA (3%) optimized in terms of viscosity and dispersibility, the central composite design based on two factors-three levels [carbopol 940 and hydroxypropyl methylcellulose (HPMC), 1-1.5% and 1-2%, respectively] was applied. The spreadability and viscosity were assessed using glass slide and rheometer, respectively. To confirm the compatibility of TXA with the gel, fourier transform-infrared (FTIR) spectroscopy was performed. Drug content uniformity was analyzed by a spectroscopy method. An ex vivo mice model using Franz cells was applied to evaluate the permeation of TXA through the skin. To investigate the effect of topical TXA gel on bleeding time, IVY human method was performed. HPMC/carbopol 940 (1:1, w/w) gel showed the highest quality in terms of viscosity and dispersibility (3.982 ± 17.6 and 6.052 ± 3.562, respectively). FTIR absorption spectrum showed that all the TXA index peaks appeared without displacement. The complete-encapsulated TXA content was uniformly dispersed throughout the gel. In vitro TXA cumulative release reached 90% in 4 h. The bleeding time determined in vivo for TXA gel was significantly lower than that for TXA solution and control. The results confirm the importance of further studies on this formulation as a potential medication to stop acute superficial bleeding.