Preservative ideals solubility

To obtain tissue preparations whose constituents were maintained as closely as possible to their state in vivo, the material had to be fixed, i.e. the enzymes inactivated so that cell structures were instantaneously preserved, an almost unattainable ideal. Formalin was the favored fixative, but others (e.g. picric acid), were also employed. Different methods of fixation caused sections to have different appearances. Further artifacts were introduced because of the need to dehydrate the preparations so that they could be stained by dyes, many of which were lipid-soluble organic molecules. Paraffin wax was used to impregnate the fixed, dehydrated material. The block of tissue was then sectioned, originally by hand with a cut-throat razor, and later by a mechanical microtome. The sections were stained and mounted in balsam for examination. Hematoxylin (basophilic) and eosin (acidophilic) (H and E staining) were the commonest stains, giving blue nuclei and pink cytoplasm. Eosinophils in the blood were recognized in this way. 

Pure benzoic acid is a white powdery crystalline solid (m.p. 122°C) only sparingly soluble in water at normal temperatures. Because of this, it is added to the drink in the soluble form of its sodium or potassium salts. It is normal practice to disperse the benzoate completely during batch makeup before addition of the acid component, with its resulting pH reduction, to avoid localised precipitation of the free benzoic acid due to its solubility having been exceeded (the solubility of benzoic acid = 0.35% m/v at 20°C). It is the free or undissociated form of benzoic acid that exhibits preservative action and hence its use is only effective when low pH values are encountered, ideally below pH 3, at which point the degree of dissociation reduces to below 10%. 

Solubility Preservatives should ideally be used at concentrations much lower than that of the main constituents of the formulation. Their solubility ought to be such that it is possible to add them as a concentrated solution and where there is no danger of creating a saturated solution. 

Thanks to its characteristics colourless and odourless, easily soluble in water and alcohol, low toxicity, good skin compatibility, broad effective spectrum , Bronopol is being used on a large scale as a preservative for cosmetics and pharmaceuticals (concentrations 0 01-01%). It is listed in the EC list of preservatives allowed for the in-can protection of cosmetics (max. authorized concentration 01% limitations and requirements avoid formation of nitrosamines). Since it is in acidic solutions that Bronopol features the highest stability, weakly acidic media are the ideal field of application. In neutral or weakly alkaline formulations there is a risk that Bronopol releases nitrite (see above) which, with defined amines and amides, forms nitrosamines and nitrosamides which are regarded as carcinogens. 

Recently, there has been an increasing interest in the use of supercritical fluid extraction (SEE) with carbon dioxide (CO2) as a solvent. This process uses the properties of gases above their critical points to extract selective soluble components from a raw material. Carbon dioxide is an ideal solvent for the extraction of natural products because it is nontoxic, nonexplosive, readily available, and easy to remove from extracted products [3,6]. SFE has the abihty to use low temperatures, leading to less deterioration of the thermally labile components in the extract. In addition, SFE is typically carried out in the absence of air which also ensures minimal alteration of the active ingredients and preservation of the curative properties [46, 47]. SC CO2 is generally efficient in the purification and fractionation of hydrophobic compounds, such as flavonoids and cinnamic acid derivatives from plant matrixes [49]. 

In Chapters 13 and 14 of this book the applications of conventional chemical catalysts were described. The use of enzymes or whole cells as catalysts for chemical transformations is well known. They can bring about various reactions at ambient temperature and pressure and afford high reaction velocities. In fact, enzymatic reaction sequences may be designed to give the ideal efficiency embodied in the second law of thermodynamics. Thus, hundreds of compounds that are very difficult to prepare by purely chemical methods may be obtained quite readily and economically with the help of enzymes. Until recently, most laboratory investigations and manufacturing processes employed soluble enzymes in dilute aqueous solutions. Before use, the required enzyme must be obtained from biological sources as a concentrated extract. It is not uncommon for a particular type of cell to contain many proteins in addition to the one desired. Therefore, the purification and concentration of enzymes in preparation for use is a very cumbersome process. When used in solution, enzyme catalysts are invariably lost after each batch operation. The use of immobilized enzymes and whole cells has been proposed as a means that could eliminate such losses and preserve hard won stocks of specialized enzymes. 

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