Freeze-drying components

C. Isolation and purification of XK-62-2 100 g of the white powder obtained in the above step B are placed to form a thin, uniform layer on the upper part of a 5 cm0X 150 cm column packed with about 3 kg of silica gel advancely suspended in a solvent of chloroform, isopropanol and 17% aqueous ammonia (2 1 1 by volume). Thereafter, elution is carried out with the same solvent at a flow rate of about 250 ml/hour. The eluate is separated in 100 ml portions. The active fraction is subjected to paper chromatography to examine the components eluted. XK-62-2 is eluted in fraction Nos. 53-75 and gentamicin Cja is eluted in fraction Nos. 85-120. The fraction Nos. 53-75 are combined and concentrated under reduced pressure to sufficiently remove the solvent. The concentrate Is then dissolved in a small amount of water. After freeze-drying the solution, about 38 g of a purified preparate of XK-62-2 (free base) is obtained. The preparate has an activity of 950 units/mg. Likewise, fraction Nos. 85-120 are combined and concentrated under reduced pressure to sufficiently remove the solvent. The concentrate is then dissolved in a small amount of water. After freeze-drying the solution, about 50 g of a purified preparate of gentamicin Cja (free base) is obtained. 

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. 

Herbal preparations may be prepared by freezedrying or air-drying. Fresh, freeze-dried leaves of nettle were shown to be effective for symptomatic relief in allergic rhinitis. The active components in nettle, histamine and acetylcholine, became ineffective when the... 

Insensitive to impact, it decomposes, sometimes explosively, above its m.p. [1], particularly if heated rapidly [2], Although used in aqueous solutions as a preservative in pharmaceutical preparations, application of freeze-drying techniques to such solutions has led to problems arising from volatilisation of traces of hydrazoic acid from non-neutral solutions, condensation in metal lines, traps or filters, and formation of heavy metal azides in contact with lead, copper or zinc components in the drying plant [3,4],... 

The physical form of the component is extremely important for ease of esterification for amylose, the order of reactivity is amylose complex > freeze-dried or freshly precipitated amylose > alcohol-precipitated, ether-dried amylose, whereas freeze-dried amylopectin is more reactive than... 

On repeated freeze-drying of microgels with EUP-components an irreversible formation of an insoluble aggregate was observed [ 135]. It was supposed that this aggregation is due to radical reactions between adjacent microgel particles. The radicals are possibly formed by a mechanical rupture of chains due to stresses within the particles caused by freezing. 

Enbrel is a product now approved for medical use that is based upon this strategy. The product is an engineered hybrid protein consisting of the extracellular domain of the TNF p75 receptor fused directly to the Fc (constant) region of human IgG (see Box 13.2 for a discussion of antibody structure) The product is expressed in a CHO cell line from which it is excreted as a dimeric soluble protein of approximately 150 kDa. After purification and excipient addition (mannitol, sucrose and trometamol), the product is freeze-dried. It is indicated for the treatment of rheumatoid arthritis and is usually administered as a twice-weekly s.c. injection of 25 mg product reconstituted in WFI. Enbrel functions as a competitive inhibitor of TNF, a major pro-inflammatory cytokine. Binding of TNF to Enbrel prevents it from binding to its true cell surface receptors. The antibody Fc component of the hybrid protein confers an extended serum half-life on the product, increasing it by fivefold relative to the soluble TNF receptor portion alone. 

Na-cefazolin is instable in its amorphous state. Takeda [1.32J described a method to ensure complete crystallization in which micro crystalline Na-cefazolin were added to at 0 °C supersaturated Na-cefazolin solution, frozen and freeze dried. The product did not contain amorphous or quasi-crystalline components. 

Flink, J. The retention of volatile components during freeze-drying A structurelly based mechanism. Freeze-drying and Advanced Food Technology, p. 351-372, 1975. Copyright 1975 Academic Press, Inc., New York, N. Y., USA... 

Sauvageot, F., Simatose, D. Some experimental data on the behavior of fruit juice of volatile components during freeze-drying. International Institute of Refrigeration (Comm. X, Paris, 1969)... 

Freezing and freeze drying of metal salt solutions, to obtain a homogeneous mixture of different components. 

The metal solutions are sprayed into cold liquids for rapid freezing, after which the droplets are freeze dried and decomposed to metal oxides. Due to the homogeneous distribution of the components, the reactions in the solid state occur at lower temperatures compared with conventionally produced powders. 

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