THE USE OF FACTORIAL DESIGN TO DEVELOP A THERMO-STABLE PULMONARY BCG VACCINE
Rajaun Ellis, Dominique Price, Pavan Muttil.
University of New Mexico, Albuquerque, NM.
Mycobacterium tuberculosis is responsible for 2 million global mortalities per year. The bacille Calmette-guérin (BCG) is a live bacterial vaccine and is the only approved vaccine against tuberculosis. It is administered via the intradermal route and is currently prepared by lyophilization. However, live vaccines prepared by lyophilization require constant cold chain storage at 4 °C, a problem in areas where tuberculosis is prevalent. In addition, the intradermal administration of these vaccines requires trained healthcare workers, due to the prevalence of needle stick injuries associated with this route of administration. Spray drying is another method of vaccine preparation and, although less widely used, several researchers have shown that spray dried vaccines can provide higher bacterial viability at elevated temperatures. This could potentially eliminate the need of cold chain storage in maintaining BCG efficacy. Furthermore, dry powders can be delivered via the pulmonary route, thereby decreasing training requirements for healthcare workers. In this study, we aimed to create a BCG dry powder suitable for pulmonary delivery using a factorial design to evaluate the variable parameters of excipient concentration, feed rate, and outlet temperature. The excipients L-leucine, bovine serum albumin, polyvinylpyrrolidone, mannitol, and trehalose were chosen for the experiments. Powders were characterized based on their size, yield, water retention, water uptake, and glass transition temperature (Tg), and then the best performer was spray dried with BCG. We expect that dry powders formulated using factorial design will reveal ideal excipient mixtures and parameters for the formulation of a stable pulmonary BCG vaccine.