VIAL LYOPHILIZATION - CALCULATIONS ON RATE LIMITATION DURING PRIMARY DRYING

Purpose. The aim of this study was to assess the rate limiting factors in the sublimation phase of freeze drying and to propose a simple mod el on the basis of these rate limitations. Methods. A programmable fre eze dryer was used. The load consisted of vials of varying size and va rious contents. To increase heat transfer, conductive paste was applie d while the resistance toward mass transport was varied by using diffe rent restrictive capillaries. Results, It was found that heat transfer limits the rate of sublimation. Presence of the commonly used excipie nt mannitol did not have a consequence on the rate of sublimation. The same applied for the restrictions towards mass transport. It was foun d that there exists not only a barrier against heat transport under th e vial, but also between the glass wall and the frozen solution. Concl usions. From the results, a set of equations is proposed that enables to predict optimum sublimation conditions. For the pharmaceutical tech nologist this can serve as a simple and useful tool to derive a suitab le freeze drying program.