Design and Evaluation of Losartan Transdermal Patch by Using Solid Microneedles as A Physical Permeation Enhancer.

Abstract

The development of a losartan potassium patch for the treatment of hypertension showed that a combination of hydrophobic and hydrophilic polymers, using as a plasticizer citroflex and succinic acid as a cohesion promoter result in homogeneous films. The effect of the Eudragit^® E100, PVP K30, citroflex and succinic acid in the bioadhesion, postwetting bioadhesion, resistance to rupture and drug release, was studied. The succinic acid in synergy with the plasticizer (citroflex) modifies the characteristics of the polymeric matrix of Eudragit^® E100, increasing the release and the resistance to rupture of transdermal patches. For the case of the hydrophilic polymer PVP K30, it increases the bioadhesion and drug release by creating porous matrices. From a previous experimental design, the optimal formulation was acquired, and this formulation was physicochemically characterized. A transdermal patch was obtained with the next dimensions and characteristics: 28.46 ± 0.055 mm in diameter and 0.430 ± 0.008 mm in thickness, a bioadhesion of 1063.05 ± 60.33 gf, postwetting bioadhesion 995.9 ± 72.53 gf significantly decreased. The breaking strength was of 1301.5 ± 96.5 gf, surface pH patch of 6, constriction of 0% at 7 days, and 94.0366 ± 1.8617% of losartan content. The 93% of the drug is released at 4 h (n = 6), adjusting to the kinetic model of Higuchi and Peppas. In the in-vitro penetration studies by passive diffusion, a flow (J) of 42.2 μg/cm²h, a permeability constant (kp) of 2.1793E-03 cm/h and a latency time (t_L) of 17.20 h and with the use of microneedles a flow (J) of 61.7 μg/cm²h, a permeability constant (kp) of 3.1869E-03 cm/h and a latency time (t_L) of 17.74 h were obtained.