In vitro testing of a pulsatile delivery system and its in vivo application for immunisation against tetanus toxoid

Abstract Problems such as patient compliance and overdosing call for the development of pulsatile drug delivery devices. The in vitro and in vivo testing of a pulsatile delivery device for tetanus toxoid are described. In vitro release studies indicate that the delivery of the entrained active is dependent upon the driving mechanism, a fluid-activated swelling agent. The delivery profile is influenced by the physicochemical properties of the biomaterials used to construct the implant, such as polyethylene porosity, excipients and the design properties of the device. Solid formulations of tetanus toxoid antigen were intermittently released into the subcutaneous tissues in sheep using the delivery device. The in vivo release of the lyophilised and compressed powder of tetanus toxoid containing excipient materials (including lactose, cellulose and magnesium stearate) was monitored indirectly by measuring levels of antibodies against tetanus toxoid in sera of mice and sheep. The antibody titres generated by our devices were no different to the titres generated by subcutaneous injection of an alum-adjuvanted liquid formulation of tetanus toxoid. The pulsatile delivery devices described should facilitate the delivery of most vaccine antigens and pharmaceuticals.