Transcutaneous permeation enhancer complex for polymer-based transdermal patches

Selecting a permeation enhancer complex (PEC) for inclusion in a matrix-type transdermal patch (TP) is a primary task in creating a new dosage form with percutaneous administration. Objective: to develop a biologically safe PEC capable of regulating percutaneous diffusion of low-molecular-weight drugs from the polyacrylate matrix of a TP and without causing adverse skin reactions. Materials and methods. The PEC contained apricot kernel oil, dioctyl sodium sulfosuccinate, dihydroquercetin and alpha-tocopherol acetate – substances that have a good impact on the functional properties of polymer-based TPs. Low-molecular alcohol-soluble drugs (chlorpropamide, caffeine and sodium benzoate and lidocaine hydrochloride) used to treat diseases of various etiologies were used as active ingredients. In vitro studies of percutaneous drug delivery were carried out on male Chinchilla rabbits in Franz glass diffusion cells using a drug diffusion analyzer. Using spectrophotometry and high-performance liquid chromatography, concentrations of drugs in aqueous solutions and in the blood plasma of the laboratory animals were measured. The irritant effect of the lidocaine-loaded transdermal polymeric matrix was tested on sexually mature young male New Zealand White rabbits. Results. When PEC was introduced into the polymer matrix film, percutaneous diffusion of the drugs increased significantly from 2.1 ± 0.4 to 9.2 ± 1.4 mg over 24 hours of experiment for the chlorpropamide-loaded TP and from 9.2 ± 1.2 to 35.2 ± 7.5 mg for the caffeine-loaded TP. Additionally, there was a 1.7- and 2.9-fold decrease and a 2.3- and 2.7-fold increase in the time to reach a constant drug concentration in blood for the chlorpropamide- and caffeine-containing TPs, respectively. Using the lidocaine- and chlorpropamide-loaded TPs, it was shown that the presence of PEC in the polymer matrix film causes no skin irritation and that the shelf life of the transdermal form increases from 1 to 3 years. Conclusion. Introduction of the proposed PEC into the polymeric matrixes of TPs enhanced percutaneous diffusion of the drugs, reduced skin irritation from the TP components, and increased the shelf life of the finished dosage forms.

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