Abstract
Prevention and treatment of arterial hypertension is of great importance. Improvement of existing medicines through the use of alternative routes of administration can enhance the pharmacotherapeutic characteristics of active pharmaceutical ingredients (APIs). Transdermal therapeutic systems (TTS) allow for delivery of a drug through intact skin into the systemic circulation, while minimizing side effects. The development of transdermal formulations of antihypertensive drugs, Lisinopril dihydrate in particular, has practical and scientific significance. Optimization of the algorithm for the development of transdermal drugs involves in vitro preformulation studies of the membrane permeability of APIs and the identification of factors that affect this process.
The tests were performed by dialysis through a semipermeable hydrophilic membrane using a Valia-Chien diffusion device. The effect of the initial concentration of Lisinopril dihydrate on the flux rate Is was investigated. Different donor concentrations of Lisinopril dihydrate were tested at three levels, 10, 20 and 30 mg/ml, accordingly. It was noted that the permeation process of Lisinopril dihydrate under model conditions corresponds to zero-order kinetics and is characterized by a uniform speed. The correlation coefficient (R2) for all the kinetic equations was 0.999. A linear dependence of the flux velocity of Lisinopril dihydrate on the initial concentration was indicated. The concentration of Lisinopril dihydrate in the donor solution of 30 mg/ml was found to be optimal for further stages of pharmaceutical development of the transdermal formulation. The studies of Lisinopril dihydrate permeability allow to give a positive assessment of the acceptability of this API for use in the transdermal formulation and the development of TTS.