Freeze-drying of aqueous solutions: Maximum allowable operating temperature

Bellows, R. J.; King, C. Judson

doi:10.1016/0011-2240(72)90179-4

Cited by 89 publications

(45 citation statements)

References 7 publications

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“…Given that a temperature increase of 1°C may lead to a reduction in primary drying time of 13% (Pikal, 1985), the economic importance of choosing the drying temperature on a rational basis is clear. Product collapse during drying has been discussed in detail by Bellows and King (1972), Pikal and Shah (1990) and more recently Sun (1997) and is associated with viscous flow of the amorphous material; this phenomenon leads to an inelegant product but may also increase reconstitution times and residual water levels. It is therefore essential to dry the material below the collapse temperature (T c ) which, for most practical purposes, is : 20°C above T g % (Sun, 1997).…”

Section: Primary Dryingmentioning

confidence: 99%

The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems

Craig

1999

International Journal of Pharmaceutics

416

204

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Section: Primary Dryingmentioning

confidence: 99%

The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems

Craig

1999

International Journal of Pharmaceutics

416

204

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“…The goal is to avoid product degradation, in particular in case of pharmaceutical and biopharmaceutical formulations, and also the collapse (or the shrinkage) of the dried product (the so called "cake") in case aqueous solutions containing amorphous products are processed, as this threaten the elegance of the cake and the product could show a higher reconstitution time and a higher amount of residual humidity. In case aqueous solutions containing crystalline products are processed, the limit value is the eutectic temperature, in order to prevent product melting [6][7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Computer-Aided Framework for the Design of Freeze-Drying Cycles: Optimization of the Operating Conditions of the Primary Drying Stage

Fissore

Pisano

2015

Processes

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This paper deals with the freeze-drying process and, in particular, with the optimization of the operating conditions of the primary drying stage. When designing a freeze-drying cycle, process control aims at obtaining the values of the operating conditions (temperature of the heating fluid and pressure in the drying chamber) resulting in a product temperature lower than the limit value of the product, and in the shortest drying time. This is particularly challenging, mainly due to the intrinsic nonlinearity of the system. In this framework, deep process knowledge is required for deriving a suitable process dynamic model that can be used to calculate the design space for the primary drying stage. The design space can then be used to properly design (and optimize) the process, preserving product quality. The case of a product whose dried layer resistance, one of the key model parameters, is affected by the operating conditions is addressed in this paper, and a simple and effective method to calculate the design space in this case is presented and discussed.

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“…Collapse in a given region of the product results from surface tension induced viscous flow of the amorphous phase after the icevapor interface has moved past that particular region (4). When performing primary drying above T c , one may observe loss of structure (denoted as "shrinkage" or "collapse") in the dried region adjacent to the ice-vapor interface due to a glass transition in the amorphous product (6). Shrinkage or collapse may compromise the (predefined) product quality attributes, e.g., product stability, residual moisture content of the cake, reconstitution times, etc.…”

Section: Introductionmentioning

confidence: 99%

Freeze-Dry Microscopy: Impact of Nucleation Temperature and Excipient Concentration on Collapse Temperature Data

2009

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Abstract. The objective of this study was to investigate the impact of nucleation temperature (T n ) and excipient concentration on the collapse temperature data obtained from freeze-dry microscopy (FDM) experiments. T n , the temperature of the onset of collapse (T oc ), and the full collapse temperature (T fc ) were determined for aqueous solutions of polyvinylpyrrolidone (PVP) 40 kDa and 2-(hydroxypropyl)-ß-cyclodextrin. Concentrations were varied from 1% to 20% (w/w) for PVP and from 1% to 30% (w/w) for the 2-(hydroxypropyl)-ß-cyclodextrin. Mutual correlation coefficients were calculated for the observed T n , T oc , and concentrations of the solutions. In addition, outliers were detected and eliminated by applying the leaving-one-out routine and calculating correlation coefficients without it. T n was found to be non-correlated with concentrations and only weakly correlated with T oc . The correlation between these two temperatures was particularly poor for the solutions of the highest and lowest concentrations. In contrast, T oc correlated much better with the corresponding concentrations, resulting in a quadratic fit for PVP and a linear fit for 2-(hydroxypropyl)-ß-cyclodextrin.

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Freeze-drying of aqueous solutions: Maximum allowable operating temperature

Cited by 89 publications

References 7 publications

The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems

The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems

Computer-Aided Framework for the Design of Freeze-Drying Cycles: Optimization of the Operating Conditions of the Primary Drying Stage

Freeze-Dry Microscopy: Impact of Nucleation Temperature and Excipient Concentration on Collapse Temperature Data

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