Polycationic Polymers and Drugs: Investigations into Interactions between Acyclovir and Polymers

S.      Jacobsen; A.      Ostmann

doi:10.2174/1573406411006040200

Abstract

Interactions between pharmaceutical ingredients play an important role in the development of drug formulations. It was the aim of our present studies to investigate drug-polymer interactions. Interaction of the antiviral drug acyclovir with polyethylenimines, polyvinylamines and the non-ionic PVP was investigated using a modified equilibrium dialysis. The membrane was only permeable to free acyclovir, while polymers and acyclovir-polymer-associates did not pass through. Significant amounts of acyclovir were bound with the polyethylenimines. The formation of associates consisting of acyclovir and either PVP or polyvinylamine could not be demonstrated. In solutions of acyclovir and polyethylenimine (Mr=25000) the amount of bound drug is increased with increasing concentration of acyclovir. Between 7.9 μg and 31.7 μg take part in the formation of associates. Differences in the osmotic pressure of the solutions do not play an important role in the permeation of acyclovir. In solutions containing acyclovir and high molecular weight polyethylenimine (Mr=750000) the bound amount of drug increases with increasing acyclovir concentration up to c0=400μg/100 ml. Further addition of free drug to the solution does not change the amount of bound drug significantly, due to possible limitations in the binding capacity. Molecular modeling investigations were performed. According to the calculations, about 85% of the interactions can be attributed to electrostatic interactions.

Keywords: Acyclovir, drug-polymer interactions, equilibrium dialysis, molecular modeling, polyethylenimine, polyvinylamine, polyvinylpyrrolidone, Polycationic Polymers, non-ionic PVP, cationic polymers, phenols, azo-dyes, sodium dodecyl sulphate, antiviral, PVP K30, dialysis membrane, Transwell™ systems, high performance liquid chromatography, UV-detector, semi-micro-osmometer, program HyperChem™, Polak-Ribiere, antiviral drug, acy-clovir-polyethylenimine interaction, drug-PEI complexes, imidazole ring, hydrogen bonding, equilibrium dialysis method