Surfactant-rich biocompatible microemulsions as effective carriers of methylxanthine drugs

Abstract

Under the perspective of their potential pharmaceutical applications, new surfactant-rich biocompatible microemulsions were prepared and structurally characterized to be used as novel carriers of theophylline and theobromine. The existence of single phase regions was investigated in pseudo-ternary phase diagrams of three different microemulsion systems: (1) isopropyl palmitate/Triton X-100/water+propylene glycol, (2) Miglyol 818/Triton X-100/water+propylene glycol and (3) isopropyl palmitate/Triton X-100+Span 20/water+propylene glycol. Electrical conductivity measurements indicated the formation of water-in-oil (w/o) structures. Interfacial properties of the microemulsions were studied by electron paramagnetic resonance (EPR) spectroscopy employing the nitroxide spin probe 5-doxylstearic acid (5-DSA). The determined order parameter and wobbling angle showed that the system composition influences the membrane flexibility whereas drug incorporation resulted in more flexible membranes. Particle size measurements were performed using dynamic light scattering (DLS) showing that addition of the drugs resulted in the formulation of larger aqueous droplets. To evaluate the ability of the proposed microemulsions to serve as carriers of bioactive compounds for topical administration, in vitro permeation studies were carried out using the Franz type diffusion cells and a model membrane. The nature of the oil and the surfactant used for the construction of the microemulsions affected the phase behavior, the size and also the interfacial properties of both free and loaded systems. Drug permeation studies revealed the effectiveness of the proposed formulations as carriers of theophylline and theobromine.