Pharmaceutical applications hydrates

Han, J. Gupte, S. Suryanarayanan, R. Applications of pressure differential scanning calorimetry in the study of pharmaceutical hydrates. II. ampicillin trihydrate. Int. J. Pharm. 1998, 170, 63-72. 

The characterization of pharmaceutical hydrates must be sufficient to provide confidence that the behavior of the material is predictable and reproducible. This requires the application of considerable molecular level intuition along with the available data. Data from all the techniques discussed are not always available, so in the absence of a complete data set the gaps must be filled using the types of energetic and structural principles described in the earlier chapter [1], When the available data are consistent with what is expected from these relation-... 

The plate dryer is limited in its scope of apphcations only in the consistency of the feed material (the products must be friable, free flowing, and not undergo phase changes) and diying temperatures up to 320°C. Applications include speci ty chemicals, pharmaceuticals, foods, polymers, pigments, etc. Initial moisture or volatile level can be as high as 65 percent and the unit is often used as a final dryer to take materials to a bone-dry state, if necessary. The plate dryer can also be used for heat treatment, removal of waters of hydration (bound moisture), solvent removal, and as a product cooler. 

Hydration can be an important factor in diffusion and mass transport phenomena in pharmaceutical systems. It may alter the apparent solubility or dissolution rate of the drug, the hydrodynamic radii of permeants, the physicochemical state of the polymeric membrane through which the permeant is moving, or the skin permeability characteristics in transdermal applications. 

Ab initio methods for polymorph, hydrate and solvate prediction are highly prized by the industry and good progress has been made in this field in recent years. This work is still a number of years from routine commercial application however, and polymorph screening experiments together with crystal structure determination, remain critical tasks for today s Pharmaceutical companies. 

Of common interest in this area are predominantly hexafluoroacetone (HFA, a gas), because of its chemical reactivity as an intermediate and the solvent power of its liquid or low melting hydrates, and perfiuoro(methyloxirane) (perfiuoropropylene oxide, HFPO, a gas), used as an intermediate and building block with many applications for functional oils and polymers.1 Hexafluoroacetone is used for the synthesis of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), pharmaceuticals, agrochemicals and polymers. Toxic properties of some species are listed in Tabic 10. 

Turpentine. Turpentine is used directly as a solvent, thinner, or additive for paints, varnishes, enamels, waxes, polishes, disinfectants, soaps, pharmaceuticals, wood stains, sealing wax, inks, and crayons, and as a general solvent. The chemistry of its mono-terpenes offers many possibilities for conversion to other substances, as illustrated in Fig. 28.20. There is increasing use of turpentine to produce fine chemicals for flavors and fragrances. An important use of turpentine is in conversion by mineral acids to synthetic pine oil. It also is a raw material for making terpin hydrate, resins, camphene, insecticides, and other useful commodities. These uses are included in the following summary of its applications. 

Plants represent a very important role in human nutrition, due to the large quantities of proteins, carbon hydrates, lipids, vitamins, antioxidants and mineral salts that its can supply. Sometimes the nutritional aspect can be associated with the flavour and fragrance of the extracts producing a high value products. In recent years one can observe an increase in research for natural sources, in particular from plant matrices, of additives with application in the food, cosmetic and pharmaceutical industries. 

Acrolein dimer may be easily hydrated to a-hydroxyadipaldehyde, C H1( iO, [141-31-1] which may dien lie reduced to 1,2,6-hexanetriol [106-69-4]. 1,2,6-Hexanetriol, C6H1403, is used in a variety of pharmaceutical and cosmetics industry applications and is currently viewed as an alternative to glycerol as a liumectant. 

If the lakes used are aluminum lakes, the alumina substrate contains water of hydration, and the lake itself may have total moisture content of between 12 and 25%. High processing temperatures can release some of the hydrated water however, in most pharmaceutical applications this is not a problem. 

Bentonite is a naturally occurring hydrated aluminum silicate used primarily in the formulation of suspensions, gels, and sols, for topical pharmaceutical applications. It is also used to suspend powders in aqueous preparations and to prepare cream bases containing oil-in-water emulsifying agents. 

Bentonite is a native, colloidal, hydrated aluminum silicate, found in regions of Canada and the USA. The mined ore is processed to remove grit and nonswelling materials so that it is suitable for pharmaceutical applications. 

Applications 45 10 t of thionyl chloride was consumed worldwide in 1992. It is utilized as a chlorination agent e.g. for the manufacture of organic intermediates, pesticides, insecticides, pharmaceuticals, dyes and pigments. It is also utilized for the dehydration of metal chloride hydrates, the chlorination of metal oxides, as a non-aqueous electrolyte and as a cathodic material in particular types of lithium batteries. 

Smith A. Pharmaceutical and biological applications of thermal analysis studies in polymorphism and hydration. Anal Proc 1986 23 338-389. 

A Raman system was designed which can be applied noninvasively to record the depth-concentration profiles of living skin with a resolution of <5 xm (River Diagnostics, Rotterdam, Netherlands). Using laser excitation at 671 and 785nm, a custom-built detection system and software tools, various parameters of the skin can be analyzed. Due to the limited penetration (of typically 20-40 pm), most studies are restricted to the stratum corneum. Applications include the determination of (i) hydration of the skin (ii) composition of the NMF and (iii) the penetration of topically applied materials. This technique can be expected to experience growing use by skin scientists in the cosmetics, pharmaceutical and dermatological research fields. 

It was stated earlier that the vast majority of pharmaceutical solvates are hydrates. There are a few studies, however, in which other solvates of drugs have been studied. Ghosh et al. (27) examined a range of dialkylhydroxypyridones (iron chelators with possible application for the treatment of anemias) and compared their structures to their corresponding formic acid solvates. TGA was able to monitor the loss of formic acid, providing complementary information for spectroscopic studies that in turn were able to provide a molecular-level explanation for the desolvation profiles. 

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