Water-soluble drugs solubility

In the commercial extraction of alkaloids from the drugs in which they exist, the powdered drug, or an alcoholic extract of it, is treated with an alkali such as ammonia or lime to liberate the alkaloid and the alkaloid is then extracted by means of an organic solvent. The crude material thus obtained is purified and finally crystallized either as the base itself or as its water-soluble salts. 

Considerable interest has been shown ia poly(ethylene oxide) for diverse appHcations ia food, drug, and cosmetic products. Such uses fall within the scope of the Federal Food, Dmg, and Cosmetic Act. The U.S. FDA has recognized and approved the use of poly(ethylene oxide) for specific food and food packaging uses. USP/NF-grades of Polyox water-soluble resins (Union Carbide Corp.) are available for pharmaceutical appHcations. 

The process of isolation finally adopted by the former authors consists in precipitating as reineckates the water-soluble bases contained in a methyl alcoholic extract of the curare. The mixed reineckates are further purified, by solution in acetone and precipitation with water as often as may be necessary. The product so cleaned represents the bulk of the biological activity of the crude drug the mother liquors may contain curine (p. 374), which indicates a menisperm as one of the components of such curares. The mixed reineckates are then fractionated chromato-graphically over alumina and the components isolated as chlorides by the use of silver sulphate and barium chloride in succession. This process has been modified in detail by Schmid and Karrer, who have also found that with their curare, the more soluble reineckate fraction includes less potent quaternary alkaloids. 

The reaction of amines with Fl+ ions has an interesting practical application. Amines of high molar mass, frequently used as drugs, have very low water solubilities. They can be converted to a water-soluble form by treatment with strong acid. For example. 

Polyphosphazenes can be considered as biomaterials in several different ways, depending on the type of utilization one can predict for these substrates. In this regard, we will consider three different topics concerning water-soluble POPs and their hydrogels, bioerodible POPs for drug delivery systems and for tissue engineering, and the surface implications of POP films. 

It is poorly soluble in acetone, 2-butanone, ethyl acetate, acetonitrile, and DMF, and insoluble in alcohols, petroleum ether, and diethyl ether. The partition coefficients of a number of solutes between PCL and water have been measured and correlated with octanol-water partition coefficients (Fig. 9) (58,59). The linear correlation (Eq. 2) when combined with the water solubility of the solutes serves as a method of estimating the solubility of drugs in PCL from first principles. ... 

Because swelling and consequent bulk erosion induced by the water-soluble salt is not desirable, use of the low-water-solubility, sUghtly acidic salt calcium lactate was investigated (30). By using this excipient it was hoped that a lowering of the pH within the surface layers of the device would take place and release of the drug would be controlled by polymer erosion confined to the surface layers of the device. In these experiments norethindrone was replaced by the currently favored steroid levonorgestrel. 

This is illustrated in Scheme VI. The protected glyceryl derivatives are insoluble in aqueous media and appear to be hydrolytically stable. The deprotected species (structure 27) is water-soluble and hydrolyzes in aqueous media at neutral pH at 37°C to give glycerol, phosphate, and ammonia. The free hydroxyl units of the deprotected polymer provide sites for the covalent attachment of drug molecules. Water insolubility can be imparted by the use of appropriate hydro-phobic cosubstituent groups to generate solid, erodible materials. 

We have already seen how water solubility and hydrolytic degradability can be built into the carrier macromolecule by the use of specific side groups. Here we will review an additional way in which drug molecules have been Linked to polyphosphazenes—by coordination. 

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