GRAS solvents

GENERALLY RECOGNIZED AS SAFE, GRAS, SOLVENTS AND THEIR PRECURSORS... 

Selb and Gallot [214] have demonstrated that poly(styrene)-gra/f-poly(4-vinyl-N-ethylpyridium bromide) forms unimolecular micelles in water/ methanol mixtures. These experimental data can be treated as an indirect confirmation of the simulation result [97] that sufficiently long regular copolymers with amphiphilic monomer units do form intramolecular aniso-metric micellar structures in a poor solvent. 

Possible transport mechanisms in a fluid system through the membrane pores are multiple. They vary to a great extent with the membrane pore size and, to a less extent, with chemical interaction between the transported species and the membrane material. Under the driving force of a pressure gra nt, permeants (whether in the form of solvents, solutes or gases) can transport across a membrane by one or more of the mechanisms to be discussed below. The degree by which they affect permeability and permselectivity depends on the operating conditions, membrane characteristics and membrane-permeating species interactions in the application environment. 

GRA-GM was prepared simply by immersing the aminated silica plate in a dilute solution of GRA-GM. The resulting monolayer exhibited high desorption resistance even toward polar solvents because of the interactions between the GO2H groups of GRA-GM and the aminosilanized surface. In this way, a densely packed GRA-GM monolayer exhibiting a conversion into Z-isomer of ca. 90% under 365 nm light irradiation was fabricated. 

One important trend in the food industry is the increased demand for natural food ingredients free of chemicals. Therefore, special attention has been paid to alternative processes directed toward extraction solvents and techniques with both GRAS and GMP labels (Ibanez et al., 1999). Supercritical C02-extraction (SFC C02) has been used (Weinreich, 1989 Nguyen et al., 1991 Nguyen et al., 1994 Ibanez et al., 1999). Tena et al. (1997) noted that extracts from rosemary obtained by SFC C02 (35 bar at 100°C) were the cleanest extracts and provided the highest recovery of carnosic acid compared to solvent extracts (acetone, hexane, dichlor-methane and methanol) after bleaching with active carbon. Bicchi et al. (2000) reported a fractionated SFC C02 method to selectively isolate carnosol and carnosic acid at 250 atm and 60°C in the second fraction. The authors used 5% methanol to modify the dissolution power of SFC C02. 

Criteria for selecting polymorphs and solvates are shown in Table 12.2. For drug substances, hydrates are preferred over solvates of organic solvents, due to toxicity considerations. The structural solvent in marketed crystalline drugs is almost invariably water [12] or a nontoxic substance such as EtOH that is generally regarded as safe (GRAS). 

Excipient USP or EP monograph GRAS Residual solvent (PDE mg/d) FDA inactive ingredient list or marketed product... 

Figure 2.8 (A) Device combining three reservoirs for the generation of solvent gra-...

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