Example 259 freeze drying

A further approach has been to deliver drugs in the form of a powder (but without a bioadhesive carrier). For example, freeze-dried insulin has been shown to be better absorbed as a powder than in solution, although the absorption of glucagon and dihydroergotamine, when delivered from liquid or powder formulations, was equivalent. 

The competitive nature of the food and beverage industry and the need for continued improvements in cost-effective manufacturing have provided an impetus for companies to develop and use new bioseparation techniques at very large scales, for example, freeze-drying in coffee production and continuous centrifugation in brewing. 

Figure Bl.24.16. An example of the applieation of the PIXE teelmique using the NMP in the imaging mode. The figures show images of the eross seetion tlirough a root of the Phaseolus vulgaris L. plant. In this ease the material was seetioned, freeze-dried and mounted in vaeuiim for analysis. The seales on the right of the figures indieate the eoneentrations of the elements in ppm by weight. It is elear that the transports of the elements tlirough the root are very different, not only in the eases of the major elements Ca and K, but also in the ease of the traee element Zn.

Dried or freeze dried samples can be extracted with water-immiscible solvents such as EtOAc or diethyl ether. For quantitative extraction, dried samples are preferably rehydrated at different times for example, 5 to 10 min for dried mangoes, 30 min for lyophihzed red peppers and pasta. Rehydration is followed by extraction with acetone or MeOH. Bixin and norbixin from a mix dry powder of annatto and com can quantitatively be extracted with MeOH followed by acetone. In order to improve pigment recovery, extruded foods require pre-digestion with enzymes to liberate the pigment from the matrix. ... 

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. 

In the first example, procaine penicillin, an aqueous vehicle containing the soluble components (such as lecithin, sodium citrate, povidone, and polyoxyethylene sorbitan monooleate) is filtered through a 0.22 pm membrane filter, heat sterilized, and transferred into a presterilized mixing-filling tank. The sterile antibiotic powder, which has previously been produced by freeze-drying, sterile crystallization, or spray-drying, is aseptically added to the sterile solution while mixing. After all tests have been completed on the bulk formulation, it is aseptically filled. 

Figure 8 An example of the decreasing heat requirement during primary drying at a chamber pressure of 0.15 torr. 5% mannitol maintained at -20°C during primary drying. Results obtained by computer simulation of freeze drying (see Ref. 3). Heavy curve Shelf Fluid. Light curve Shelf surface. Lightweight dashed curve Product Bottom. Heavy dashed curve Sublimation.

Two special cases of radiative heat transfer which are applicable to heat transfer in freeze drying are illustrated by Figure 32. Heat transfer between body 1 and body 2 are illustrated for case I (Fig. 32a), where body 1 is of much greater area than body 2, Ai A2, and surrounds body 2. The freeze-drying example is heat exchange between the top of the vial (body 2) and the freeze dryer shelf... 

The freeze-drying process is initiated by the freezing of the biopharmaceutical product in its final product containers. As the temperature is decreased, ice crystals begin to form and grow. This results in an effective concentration of all the solutes present in the remaining liquid phase, including the protein and all added excipients. For example, the concentration of salts may increase to... 

Wiliemer, H. Freeze-drying process data determination for human blood derivates with factor VIII as example. PDA Fourth International Congress, p. 142-151, Vienna, 1996. Copyright 1996, PDA Inc. Bethesda, Maryland, USA... 

The selected examples demonstrate that there is no ideal process for the freeze drying of fee extract. One must compromise in the various steps of the whole process, from bean iction. roasting, extraction, freezing, freeze drying and packing to achieve the desired ility and cost of the freeze dried coffee. 

In Section 2.2.8, possible failures during the freeze drying process are classified in four categories, and the preventions and necessary actions briefly discussed. In this chapter, some unexpected or undesirable events are studied which, by experience may happen. The problems listed here are selected from the course of the freeze drying process. A breakdown of single components, for example pumps, compressors or valves are not included in this chapter. The list will be incomplete, but an attempt has been made to mention some of the more frequent events. The problems with leaks and their hunting is discussed in Section 2.2.8. 

I have tried to show the interconnection between the property of the product, the goal to make it stable and the necessary processes to achieve this. The problems of the different process steps are discussed with examples and the parameters are described which influence each step. I have avoided following the many theoretical attempts describing one or more of the freeze-drying steps, but have restricted myself to a few equations which permit the calculation of process and product data with sufficient accuracy, or at least, allow an estimate, if some data is mentioned. 

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