Freeze dried products

In paired comparison tests two different samples are presented and one asks which of the two samples has most of the sensory property of interest, e.g. which of two products has the sweetest taste (Fig. 38.3). The pairs are presented in random order to each assessor and preferably tested twice, reversing the presentation order on the second tasting session. Fairly large numbers (>30) of test subjects are required. If there are more than two samples to be tested, one may compare all possible pairs ( round robin ). Since the number of possible pairs grows rapidly with the number of different products this is only practical for sets of three to six products. By combining the information of all paired comparisons for all panellists one may determine a rank order of the products and determine significant differences. For example, in a paired comparison one compares three food products (A) the usual freeze-dried form, (B) a new freeze-dried product, (C) the new product, not freeze-dried. Each of the three pairs are tested twice by 13 panellists in two different presentation orders, A-B, B-A, A-C, C-A, B-C, C-B. The results are given in Table 38.3. 

The most important objective in developing a freeze-dried product is to assure that critical quality attributes are met initially and throughout the shelf life... 

Therefore, freeze-drying should be carried out at the highest allowable product temperature that maintains the appropriate attributes of a freeze-dried product. This temperature depends on the nature of the formulation. Process development and validation requires characterizing the physical state of the solute, or solutes, that result from the freezing process and identifying a maximum allowable product temperature for the primary drying process [20,21]. 

Tsai HL, Chang SKC and Chang SJ. 2007. Antioxidant content and free radical scavenging ability of fresh red pummelo [Citrus grandis (L.) Osbeck] juice and freeze-dried products. J Agric Food Chem 55(8) 2867-2872. 

Native factor VIII is traditionally purified from blood donations first screened for evidence of the presence of viruses such as hepatitis B and HIV. A variety of fractionation procedures (initially mainly precipitation procedures) have been used to produce a factor VIII product. The final product is filter-sterilized and filled into its finished product containers. The product is then freeze-dried and the containers are subsequently sealed under vacuum, or are flushed with an inert gas (e.g. N2) before sealing. No preservative is added. The freeze-dried product is then stored below 8 °C until shortly before its use. 

Fig. 1.42. Scanning electron-microscopic photographs of different freeze dried products.

The storage of a freeze dried product starts with the end of the secondary drying and its transfer into a suitable packing. In the drying plant a certain residual moisture content (RM) is achieved as a function of the product temperature and the drying time (Section 1.2.2). 

For all measurements of RM the product must be handled in such a way as to exclude water absorption from the surroundings. Filling a freeze dried product into another container and/or weighing it, should only be done in boxes or isolators filled with dry gas (see above). 

Fig. 1.101. Equilibrium water content in two different freeze dried products, each with two different amounts of product per vial. The equilibrium data are extrapolated from the +25 °C, respectively from the +40 °C values. SV1, U, SV8 see Fig. 1.100.

Nail, St. L., Johnson, W. Methodology for in-process determination of residual water in freeze-dried products. Developments in Biological Standardization, Vol. 74, p. 137-152. Acting Editors Joan C. May, F. Brown, S. Karger AG, CH-4009 Basel (Switzerland), 1992... 

Fig. 2.49.2. Schema of a freeze drying production plant with approx. 20 m2 shelf area. The chamber and condenser are in the same vacuum chamber, separated by a wall in which the valve is built, providing the shortest possible path for the water vapor. The condenser and the brine heat exchanger are cooled by LN2. The condenser surface is made from plates (Fig. 2.49.3), its temperature can be controlled between -110 °C and -60 °C. The shelves can be controlled by the circulated brine between -70 °C and +50 °C. The trays with product can be automatically loaded and unloaded from a trolley. The shelves can be pressed together in one block and the trays are loaded to the shelves by pushing one shelf after another in front of the trolley.

Vries et al. [3.59] described the development of a stable parenteral dosage form of the cytotoxic drug E 09. E 09 dissolves poorly in water and its solution is unstable. With the addition of 200 mg of lactose per vial containing 8 mg of E 09, an optimum formulation was developed with respect to solubility, dosage of E 09 and length of the freeze drying cycle. DSC studies have been used to select the most effective parameters. The freeze dried product remains stable for 1 year when stored at 4 °C in a dark environment. 

Fig. 4.4. Influence of fruit and vegetable type on color, taste and consistency of freeze dried products.

Kondou et al. [5.10] compared the production of PbCZ Tij Oj (PZT) by solid-state reaction between Ti02, Zr02PbO and the freeze drying of the nitrate salt solution. The solid state reaction requires 1100 °C, but the transformation of the freeze dried nitrates only 580 °C. Furthermore, the freeze dried product could be sintered better and showed at the Curie-temperature a two-fold larger dielectric constant than the PZT produced by solid-state reaction. 

A. Stokvold, K. Dyrstad and F.O. Libnau, Sensitive NIRS measurement of increased moisture in stored hygroscopic freeze dried product, J. Pharm. Biomed. Anal., 28, S61-S13 (2002). 

Neorecormon is one such product. Produced in an engineered CHO cell line constitutively expressing the EPO gene, the product displays an amino acid sequence identical to the native human molecule. An overview of its manufacturing process is presented in Figure 6.7. The final freeze-dried product contains urea, sodium chloride, polysorbate, phosphate buffer and several amino acids as excipients. It displays a shelf-life of 3 years when stored at 2-8 °C. A pre-filled syrine form of the product (in solution) is also available, which is assigned a 2 year shelf-life at 2-8 °C. 

Conditioning of the Product. The high porosity and low moisture content of the freeze-dried product require that the vacuum be broken and packaging he done under a dried inert-gas blanket, in many cases, to prevent oxidation during storage and maintain the low moisture content. Carbon dioxide or nitrogen are commonly used. 

---