Mass and Heat Transfer in Vial Freeze-Drying of Pharmaceuticals: Role of the Vial

Pikal, Michael J.; Roy, Michael L.; Shah, S.

doi:10.1002/jps.2600730910

Cited by 313 publications

(380 citation statements)

References 5 publications

(8 reference statements)

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“…In this study, we assume that all these contributions can be referred to the same heat transfer area. According to Smoluchowski theory, as outlined by Dushman & Lafferty (1962) and reported by Pikal et al (1984), K g is a function of the average distance between the bottom of the vial and the shelf (ℓ) and of chamber pressure: …”

Section: Theoretical Calculation Of Heat Flux In Vial Freeze-dryingmentioning

confidence: 99%

“…Each flux is proportional to the difference in the fourth powers of the absolute temperatures of the two surfaces, and to the effective emissivity for the heat exchange, which depends on the relative areas of the two surfaces, their emissivities, and a geometrical view factor. According to Pikal et al (1984) the radiative heat transfer coefficient can be written as:…”

Section: Theoretical Calculation Of Heat Flux In Vial Freeze-dryingmentioning

confidence: 99%

“…While the values of Λ 0 , λ 0 , and e s can be found in the literature, the values of the parameters K c , a c , ℓ, and e v (in case radiation from upper shelf plays an important role), have to be determined by regression analysis of experimental data, even if some values can be found in the literature for some types of vials (Pikal et al, 1984). It follows that K v ′ depends essentially on the operating conditions at which drying is carried out: chamber pressure, shelf temperature and, in turn, temperature of chamber gas.…”

Section: Theoretical Calculation Of Heat Flux In Vial Freeze-dryingmentioning

confidence: 99%

See 2 more Smart Citations

Heat Transfer in Freeze-Drying Apparatus

Pisano¹,

Fissore²,

Barresi³

2011

Developments in Heat Transfer

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Section: Theoretical Calculation Of Heat Flux In Vial Freeze-dryingmentioning

confidence: 99%

Section: Theoretical Calculation Of Heat Flux In Vial Freeze-dryingmentioning

confidence: 99%

Section: Theoretical Calculation Of Heat Flux In Vial Freeze-dryingmentioning

confidence: 99%

See 1 more Smart Citation

Heat Transfer in Freeze-Drying Apparatus

Pisano¹,

Fissore²,

Barresi³

2011

Developments in Heat Transfer

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“…[3]. It was shown that the rate of removal of water vapor from the vials during the primary drying is governed by three resistances: resistance of the dried-product layer, resistance of the vial, and the resistance of the chamber to condenser pathway.…”

Section: Introductionmentioning

confidence: 99%

Experimental Determination of the Key Heat Transfer Mechanisms in Pharmaceutical Freeze Drying

Ganguly

Nail

Alexeenko

2010

10th AIAA/ASME Joint Thermophysics and Heat Transfer Conference

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Freeze-drying is often used in manufacture of pharmaceuticals to remove a solvent in such a way that the sensitive molecular structure of the active substance of a drug is least disturbed, and to provide a sterile powder that can be quickly and completely rehydrated. In this work heat transfer rates in a laboratory-scale freeze-dryer have been measured to investigate the contribution of different heat transfer modes. Pure water was partially dried under low-pressure conditions and sublimation rates were determined gravimetrically. The heat transfer rates were observed to be independent of the separation distance between a product vial and a dryer shelf and linearly dependent on the pressure in the free molecular limit. However, under higher pressures the heat transfer rates were independent of pressure and inversely proportional to the separation distance. Previous heat transfer studies in conventional freeze-drying cycles have attributed a dominant portion of the total heat transfer to radiation, the rest to conduction, whereas the convection has been found insignificant. While the measurements revealed the significance of the radiative and gas conduction components, the convective component was found to be comparable to the gas conduction contribution at pressures greater than 100mTorr. The current investigation suggests that the convective component of the heat transfer cannot be ignored at typical laboratory-scale freeze-drying conditions.

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“…The mathematical model expressed by heat and mass transfer has been investigated for the expression of the sublimation phenomenon by many researchers. [1][2][3][4][5] In the heat and mass transfer model, two parameters, heat transfer coefficient and dry layer resistance, are important for estimating the product temperature during primary drying. The heat transfer coefficient for the estimation of the heat transfer rate depends on the lyophilizer and the glass vial container and its stopper, and is experimentally determined by a water sublimation test.…”

mentioning

confidence: 99%

Optimization of Primary Drying Condition for Pharmaceutical Lyophilization Using a Novel Simulation Program with a Predictive Model for Dry Layer Resistance

Kodama

Sawada

Hosomi

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this study was to develop a novel simulation program to accurately predict the maximum product temperature and the primary drying time in lyophilization using the predictive model for dry layer resistance, which is the resistance of dried cake against water vapor flow. Ten percent sucrose aqueous solution was selected as a model formulation. It was demonstrated that the deviations between the predicted and measured maximum product temperature were attributed to the error of dry layer resistance at a given drying condition, which was different from the measured dry layer resistance in a preliminary lyophilization run for the simulation program. However, when the predictive model of dry layer resistance was used for the simulation program, the model remarkably enhanced the accuracy of the simulation program to predict the maximum product temperature and primary drying time under various operating conditions. Furthermore, the primary drying condition required for minimized drying at a close collapse temperature was successfully discovered through one preliminary run. Therefore, it is expected that the developed simulation program is useful for designing the lyophilization cycle without a trial and error approach.Key words simulation; dry layer mass transfer resistance; maximum product temperature; primary drying time Lyophilization is widely employed in pharmaceutical industries to enhance the stability of drug products for parenteral injection. The lyophilization cycle mainly consists of three steps: freezing, primary drying, and secondary drying. Generally, the primary drying process is carried out through sublimation, and requires up to a few days. In order to maximize the sublimation rate in primary drying, it is important that the vial heat transfer rate is as high as possible, resulting in a minimized primary drying time and high product temperature. However, the maximum product temperature has to be kept below the collapse temperature, where a lyophilized cake loses macroscopic structure and collapses, to ensure the elegant appearance of the lyophilized cake and its stability. Hence, enormous efforts have been spent to minimize the primary drying time without the collapse of lyophilized cakes by adjusting the shelf temperature and chamber pressure in pharmaceutical development.In order to minimize the trial and error experiments, the mathematical model for the prediction of the optimized product temperature is thought to be useful. The mathematical model expressed by heat and mass transfer has been investigated for the expression of the sublimation phenomenon by many researchers. [1][2][3][4][5] In the heat and mass transfer model, two parameters, heat transfer coefficient and dry layer resistance, are important for estimating the product temperature during primary drying. The heat transfer coefficient for the estimation of the heat transfer rate depends on the lyophilizer and the glass vial container and its stopper, and is experimentally determined by a water sublimation test. [6][7][8] The ...

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Mass and Heat Transfer in Vial Freeze-Drying of Pharmaceuticals: Role of the Vial

Cited by 313 publications

References 5 publications

Heat Transfer in Freeze-Drying Apparatus

Heat Transfer in Freeze-Drying Apparatus

Experimental Determination of the Key Heat Transfer Mechanisms in Pharmaceutical Freeze Drying

Optimization of Primary Drying Condition for Pharmaceutical Lyophilization Using a Novel Simulation Program with a Predictive Model for Dry Layer Resistance

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