Poloxamer 407 microspheres for orotransmucosal drug delivery. Part II: In vitro/in vivo evaluation

Abstract

Aim of this research was to evaluate novel microspheres based on poloxamer 407, alone or in mixture with Gelucire ® 50/13, as possible buccal delivery system for atenolol (AT). The microspheres have been prepared by spray congealing and investigated to assess AT in vitro delivery through cellulose membranes and ex vivo permeation using porcine buccal mucosa. The microparticles were tested as such or directly compacted to obtain tablets. For comparison the physical mixtures, tablets of the physical mixtures and an AT solution were examined. Finally, the microparticles were sublingually administered in rabbits to evaluate AT pharmacokinetics compared to a market oral tablet (reference). The AT release from microspheres through the synthetic membrane was delayed with respect to the drug solution, more markedly when microparticles contained poloxamer as unique adjuvant; this formulation enhanced AT transmucosal permeation. The enhancement effect of poloxamer was confirmed by the permeation experiments on the corresponding physical mixture. Tabletting hindered both release through cellulose membranes and transmucosal permeation of drug. In vivo studies revealed that the absolute bioavailability of microsphere formulations was higher than that of reference in spite of a lower dosage of drug, suggesting a possible dose reduction by AT microparticles orotransmucosal administration.