ABSTRACT
In this study, we used novel synthetic conditions of precipitation polymerization to obtain nanosized cyproterone molecularly imprinted polymers for application in the design of new drug delivery systems. The scanning electron microscopy images and Brunauer-Emmett-Teller analysis showed that molecularly imprinted polymer (MIP) prepared by acetonitrile exhibited particles at the nanoscale with a high degree of monodispersity, specific surface area of 246 m(2) g(-1), and pore volume of 1.24 cm(3) g(-1). In addition, drug release, binding properties, and dynamic light scattering of molecularly imprinted polymers were studied. Selectivity of MIPs was evaluated by comparing several substances with similar molecular structures to that of cyproterone. Controlled release of cyproterone from nanoparticles was investigated through in vitro dissolution tests and by measuring the absorbance by HPLC-UV. The pH dissolution media employed in controlled release studies were 1.0 at 37 °C for 5 h and then at pH 6.8 using the pH change method. Results show that MIPs have a better ability to control the cyproterone release in a physiological medium compared to the non molecularly imprinted polymers (NMIPs).
Subject(s)
Cyproterone/chemical synthesis , Molecular Imprinting/methods , Nanoparticles/chemistry , Betamethasone/chemistry , Cyproterone/chemistry , Delayed-Action Preparations , Gestonorone Caproate/chemistry , Hydrogen-Ion Concentration , Light , Nanoparticles/ultrastructure , Particle Size , Polymers/chemical synthesis , Polymers/chemistry , Porosity , Scattering, Radiation , Solutions , Solvents , Spectrophotometry, InfraredABSTRACT
PURPOSE: The aim of this study was to enhance the transdermal absorption of the highly active progestin gestodene from matrix type transdermal delivery systems (TDDS) by formation of prodrugs with improved matrix solubility. METHODS: Gestodene esters were synthesized via acylation of the drug with the respective carboxylic anhydrides. Subsequently TDDS were produced using the solvent cast method. Selected formulations were examined with in vitro diffusion experiments using skin of nude mice. RESULTS: One prodrug, gestodene caproate proved to be an oil at ambient temperature and showed a very high solubilty of over 10.5% in the TDDS matrix. Within in vitro penetration studies using those systems the prodrug exhibited a significantly higher transdermal penetration rate than gestodene from reference systems. Furthermore, the prodrug was hydrolyzed to the parent drug to a high extent during the passage of the skin. CONCLUSIONS: Designing prodrugs to the requirements of matrix TDDS is an efficient way of enhancing the transdermal drug flux rate.
