Effect of primary drying temperature on process efficiency and product performance of lyophilized Ertapenam sodium

Abstract

The present work aimed to investigate the impact of primary drying temperature on lyophilization process efficiency and product performance of lyophilized Ertapenam sodium (EPM). Phase behavior of EPM formulation (200?mg/mL) using differential scanning calorimetry (DSC) and freeze drying microscopy (FDM) showed Tg′ at ?28.3?°C (onset) and Tc at ?25.0?°C (onset), respectively. The formulation was freeze dried at different product temperature (Tp) during primary drying, using (a) conservative cycle (CC) where the maximum Tp (?31.9?°C) <Tg′, (b) aggressive cycle 01 (AC01) where the maximum Tp (?24.8?°C) >Tg′, and (c) AC02 where the maximum Tp (?21.0?°C) >Tc. The drying kinetics revealed that the sublimation rate was increased from 0.128?g/h/vial in CC to 0.159 and 0.182?g/h/vial in AC01 and AC02, respectively. This ultimately reduced the primary drying time of 208?min in CC to 145?min in AC01 and to 103?minutes in AC02. Morphological evaluation of cake using scanning electron microscopy (SEM) and texture analysis revealed that AC01 lead to induction of microcollapse, whereas AC02 resulted in collapsed cake. Furthermore, the microcollapsed formulations showed similar physicochemical stability to CC formulation, whereas collapsed cake showed significant degradation of EPM and increased degradation on stress stability. The study highlights that primary drying with microcollapse can be utilized to improve the process efficiency without compromising product quality of amorphous EPM.