Choked flow and importance of Mach I in freeze-drying process design

Patel, Sajal M.; Chaudhuri, Swetaprovo; Pikal, Michael J.

doi:10.1016/j.ces.2010.07.024

Cited by 77 publications

(50 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some other complications can arise because of dryer limitations in heat and mass transfer. High flow rates at low chamber pressure may result in "choked flow" and loss of pressure control [28]. Condenser and/or refrigeration system limitations may also result in loss of pressure control.…”

Section: Dryer Loadmentioning

confidence: 99%

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

Wang

McCoy²,

Pikal

et al. 2015

Lyophilized Biologics and Vaccines

Self Cite

View full text Add to dashboard Cite

Section: Dryer Loadmentioning

confidence: 99%

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

Wang

McCoy²,

Pikal

et al. 2015

Lyophilized Biologics and Vaccines

Self Cite

View full text Add to dashboard Cite

“…However, a vapor tube of sufficient dimensions is a prerequisite to apply the TDLAS technique to any lyophilizer. Nevertheless, the TDLAS sensor has been shown to be applicable to estimation of K v [17], R p  [20], product temperature at the vial bottom and sublimation interface [17], residual moisture content [18], and choked flow limits of a lyophilizer [7,15,21]. The principle of TDLAS and its application in lyophilization are described later in this chapter.…”

Section: Coupling Of Lyophilization Process and Product Attributes: Lmentioning

confidence: 99%

“…Figure 3 shows a graph of the sublimation rate as a function of chamber pressure used to construct the design space for the primary drying stage. The area "choked flow regime" represents the equipment limitation to support the "maximum" mass flow during primary drying [21] and therefore shelf temperature and chamber pressure conditions generating mass flow of water vapor in the "choked flow regime" should be avoided. In cases where the condenser design is the limiting factor in achieving the target mass flow, the choked flow regime is replaced with the "condenser overload regime.…”

Section: Lyophilization Design Space For Primary Dryingmentioning

confidence: 99%

See 1 more Smart Citation

Advances in Instrumental Analysis Applied to the Development of Lyophilization Cycles

Kessler

Sharma²,

Mujat

2015

Lyophilized Biologics and Vaccines

View full text Add to dashboard Cite

The lyophilization process is commonly used to formulate compounds that are unstable in aqueous solution. In order to develop a successful lyophilization process, a comprehensive understanding of the physical and chemical characteristics of formulations in the frozen and freeze-dried form is essential.The three crucial steps in the lyophilization process are: freezing, primary drying, and secondary drying. The freezing process involves transformation of a liquid formulation to a frozen state. During this transformation, the key transition events are ice nucleation, crystallization of water, and simultaneous increase in solute concentration. Once the formulation is frozen, crystalline components crystallize out. Most disaccharides and proteins tend to remain in an amorphous phase and at the end of the freezing step may contain up to ~ 20 % of supercooled water. These transitions during the freezing process can be illustrated using a state diagram of a binary solution of sucrose and water (Fig. 1) [1]. Point A shows the initial temperature and composition of the liquid formulation. As the solution is cooled, ice nuclei form in the solution (point B). This event typically occurs below the thermodynamic equilibrium freezing point of the formulation. Ice nucleation is an exothermic event that leads to an increase in the solution temperature (point C). As the solution is further cooled, the solutes (such as buffer salts) may crystallize out (point D) at the eutectic temperature ( T eu ). For a binary system, W e represents the weight of crystalline solute at T e . If the solutes remain amorphous (example sucrose), a glass transition event is observed (point E) at the glass transition temperature of the maximally freeze-con-

show abstract

“…These theoretical models can be used to predict the effect of various process parameters (shelf temperature, ramp rate, chamber pressure, sublimation rate, and drying time) on critical product quality attributes (product temperature, residual water). Such an approach helps in creating the design space wherein the process will operate without any problems and at the same time meet the product specifications (38). Also, theoretical modeling minimizes the number of experiments required during process development and scale-up.…”

Section: Theoretical Modelingmentioning

confidence: 99%

Emerging Freeze-Drying Process Development and Scale-up Issues

Patel¹,

Pikal

2011

AAPS PharmSciTech

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Choked flow and importance of Mach I in freeze-drying process design

Cited by 77 publications

References 7 publications

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

Advances in Instrumental Analysis Applied to the Development of Lyophilization Cycles

Emerging Freeze-Drying Process Development and Scale-up Issues

Contact Info

Product

Resources

About