Emerging Freeze-Drying Process Development and Scale-up Issues

Abstract

Abstract. Although several guidelines do exist for freeze-drying process development and scale-up, there are still a number of issues that require additional attention. The objective of this review article is to discuss some emerging process development and scale-up issue with emphasis on effect of load condition and freeze-drying in novel container systems such as syringes, Lyoguard trays, ampoules, and 96-well plates. Understanding the heat and mass transfer under different load conditions and for freeze-drying in these novel container systems will help in developing a robust freeze-drying process which is also easier to scale-up. Further research and development needs in these emerging areas have also been addressed.

Application of freeze-drying in the development of oral drug delivery systems

“…The water crystallizes, causing the remaining solution to become more concentrated, thereby forming a 'freeze-concentrate'. Some of the drugs and excipients present in the formulation may crystallize or become amorphous in the freeze-concentrate [6]. The crystallization of solutes from the concentrated solution may form a eutectic mixture with ice, whereby two or more crystalline solids coexist intimately and the mixture melts like a pure single compound [7].…”

“…Most of the water removal during freeze-drying is mainly effected through sublimation of the crystalline water under conditions well below the vapor pressure of water. It is imperative that the drying temperature in the primary drying stage does not exceed the critical eutectic (T e ) or glass transition (T g ') temperature of the crystalline or amorphous materials respectively, as this would result in a 'meltback' or 'collapse' phenomenon [6,8].…”

Formulation Development for Antibody-Drug Conjugates

“…However, lyophilization is not a panacea for all stability problems (Roy and Gupta 2004). Rational design of stable lyophilization formulations has been extensively reviewed (Carpenter and Manning 2002;Rey andMay 2010;Nireesha et al 2013;Patel et al 2013;Johnson and Lewis 2011). While it is typically assumed that enhanced stability can be achieved at low moisture level, work has also been conducted on the effect of surface area on the physical and chemical stability of the proteins (Johnson and Lewis 2011;Abdul-Fattah et al 2007a, b, c, 2008Luthra et al 2008;Chang et al 2005).…”

Spray-Drying of Biopharmaceuticals

“…First, specific to the manufacturing process, spray-drying is more easily scaled to the industrial production level and has lower initial investment costs [3]. The processing time is much shorter for spray-drying, which is on the order of hours, than for freeze-drying which can take days [51]. Spray-drying is a one-step process, whereas freeze-drying may require another milling procedure to form particles.…”