Differential freeze-drying

Hatley, R. H. M. The effective use of differential scanning calorimetry in the optimisation of freeze-drying processes and formulations. Developments in Biological Standardization Vol. 74, p. 105-122. Acting Editors Joan C. May, F. Brown S. Karger AG, CH-4009 Basel (Switzerland), 1992... 

One part of commercial defatted soy flakes was extracted with ten parts of dilute NaOH (pH 9-10). After removal of spent flakes, the total extract was adjusted to pH 4.5 with dilute HCl to precipitate the curd. The curd was washed three times with H2O, resuspended at pH 7.0, and freeze dried. Intrinsic viscosity, optical rotation, and differential scanning calorimetry (DSC) measurements show the soluble fraction of curd to be native. 

A constant strain rate of 10% per minute was employed. Polymers were isolated by air drying or freeze drying and molded at 150°C into dumbbell speciments for the tensile measurements. Glass transition temperatures (Tg) were measured by differential scanning calorimetry. 

A DuPont Model 990 thermal analyzer equipped with a Model 910 DSC cell base was used for differential scanning calorimetry. Samples were analyzed as 15 (w/w) solutions of freeze-dried RDP which had been dialyzed to remove excess buffer salts. A heating rate of 5°C/min was used runs were performed in a nitrogen atmosphere (5 psi). A known weight of water was used in the reference pan to balance the heat capacity of the sample pan. 

Micrographs of the freeze-dried RDP preparations are shown in Figure 6. The unheated and microwave treated samples are clearly differentiated from those treated with hot water. The former consist of ragged fragments containing numerous but small pores while the latter appeared more aggregated and exhibits larger orifices. A consideration of bulk density (Table IV) and microstructure may help to explain some aspects of protein/water interaction properties. Porosity and particle size could be important parameters, however they are difficult to control and are rarely measured in studies of functional properties. 

The possible change of structure during loading can be evaluated by measurements, e.g., with the ER or differential scanning calorimetry (DSC) method, and can be confirmed by freeze-drying samples exposed to the shelf temperature for a prolonged time. 

It is important to select the components of the substrates with care and particularly to pay attention to the physical parameters they act upon, in particular the vitreous transition temperature (7g ) of the deep-frozen vaccine [20-25,30]. This temperature, also referred to as vitreous eutectic temperature, does indeed play a critical role in the deformation and collapsing of freeze-dried pellets [20,25], and possibly in the loss of infectivity titers. This temperature is dependent on the nature and concentration of the substrate molecules and may be determined in several ways [20,29,35,36]. In industrial practice, the most commonly utilized techniques are differential scanning calorimetry (DSC) as well as resistance and/or dielectric constant measurements. 

Martini, A. Kume, S. Crivellente, M. Artico, R. Use of subambient differential scanning calorimetry to monitor the frozen-state behaviour of blends of excipients for freeze-drying PDA. J. Pharm. Sci. Technol. 1997, 51, 62-67. 

Murase, N. Echlin, P. Franks, F. The structural states of freeze-concentrated and freeze-dried phosphates studied by scanning electron-microscopy and differential scanning calorimetry. Cryobiology 1991, 28 (4), 364—375. 

Kassraian, K. Spitznagel, T. Juneau, J. Yim, K. Characterization of the sucrose/glycine/water system by differential scanning calorimetry and freeze drying microscopy. Pharm. Develop, and Technol. 1998, 3, 233-239. 

An instrument performing measurements of D2 (viz. the ratio of the resistivity of ice to that of a product at a given temperature) and implementing DTA (differential thermal analysis) was developed to control freeze-drying processes the principal components are a test chamber, a cooling and heating unit, a digital computer system and a printer. It was used to evaluate the thermal features of a 20% sucrose solution [12]. 

Samples (1.0 tol.5 g) of the freeze-dried product were equilibrated over saturated salt solutions at 25°C, in order to achieve water activities between 0.11 and 0.90 (Spiess and Wolf, 1983). After equilibration (about 2 to 3 weeks), small samples were taken for DSC analyses and the remaining material was used to determine equilibrium moisture content. Phase transitions were determined by differential scanning calorimetry using a DSC TA2010 controlled by a TA5000 module (TA Instruments, Newcastle, USA). Samples of about 10 mg ( 0.01), conditioned in TA aluminum pans... 

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