In vivo study of different ointments for drug delivery into oral mucosa by EPR oximetry

The aim of the present study was to determine the rate of transport and long-term effect of a drug applied to the oral mucosa in different ointments. Three ointments with bioadhesive properties: Orabase, Carbopol 935P, and polymethyl methacrylate (PMM) and the ointment Miglyol without such properties were used. Benzyl nicotinate (BN) was used as an active ingredient that causes hyperemia. The kinetics of drug action was measured by electron paramagnetic resonance (EPR) oximetry in vivo using the paramagnetic probe (Lithium phthalocyanine) implanted beneath the epithelium of the buccal mucosa in rats. EPR spectra line-width was proportional to local changes of partial pressure of oxygen (pO(2)) in tissue and was monitored for 90 min after the application of ointments mixed with BN. The greatest increase in pO(2) and the highest efficiency of drug action was observed after the application of 2% BN in PMM (P<0.01). Additionally in PMM the drug effect increased linearly with BN concentration up to 3%, at higher concentrations (3.5 and 4% BN) no further effect was observed. The results demonstrated that the greatest and the longest effect caused by a hyperemic drug in PMM. By increasing the concentration of the drug in PMM higher pO(2) in the oral mucosa can be established but only until the saturation is reached.