Caffeine, solubilization

One of the classic examples in this series is the solubilization of p-amino-benzoic acid (PABA) by caffeine [51], for which the essential data are summarized in Fig. 9. The solubility of PABA in the absence of caffeine was reported to be 6.2 mg/ml, which could be increased to 7.7 mg/ml by the addition of at least 2 mg/ml of caffeine. The linear increase in PABA concentration as a function of caffeine concentration is consistent with the formation of a 1 1 stoichiometric complex. From the data obtained in the linear concentration region, a value of 48 L/mol was calculated for K. Further increases in the caffeine concentration up to 6 mg/ml had no effect on the PABA solubility. However, larger concentrations of caffeine led to a reduction in the dissolved... 

Triacetin is the triacetate ester of glycerol and is used in many over-the-counter products. For example, triacetin solubilizes 500 mg of acetaminophen, 60 mg of caffeine, and 15 mg of pyrilamine maleate in Midol Maximum Strength gelcaps. 

Reverchon E, Donsi G, Gorgoglione D. Salicylic acid solubilization in supercritical CO2 and its micronization by RESS. J Supercrit Fluids 1993 6 241-248. Subra P, Boissinot P, Benzaghou S. Precipitation of pure and mixed caffeine and anthracene by rapid expansion of supercritical solutions, Proceedings of the 5th meeting on Supercritical Fluids. Vol. 1. Perrut M, Subra P, ed. 23-25 March, Nice, France, 1998 307-312. 

Complexation. It has been well established in the literature that complexation is an effective way to solubilize hydrophobic compounds. Nicotinimide is known to complex with aromatic drugs through tt donor-7r acceptor interaction (101). Similar tt-tt interaction also occurs between salts of benzoic acid or salicylic acid and drugs containing aromatic rings such as caffeine (102).Obviously, aromaticity is an important factor in this type of complexation. Unfortunately, from a safety perspective the use of these types of complex-ing agents for products is not really very viable. 

King and Solms (1981) have shown that caffeine-chlorogenic complex, i.e. caffeine, chlorogenic acids and also phenols, are effective solubilizers of flavor compounds. This property could be of interest for modifications of the flavor quality. 

Plates, leaflets from acetore-alc, faint greenish-yellow tinge, tnp 122-123. Maximum fluorescence at 440 nm C.A. 38, 1276 (1944), Freely sol in benzene moderately sol in acetone slightly so] in alcohol. Insol in water. May be solubilized in water by purines such as caffeine, tetramethyl-uric acid- The nucleosides, adeDOStne, and guanosine also show a solvent action. 

Nicotinamide, or vitamin B3, characterized by a low toxicity, has been proven to solubilize a number of drugs, such as, for example, riboflavin (35) and nifedipine (36). A 36-fold increase of the solubility of riboflavin, which has a multi-aromatic ring system, at nicotinamide concentrations of about 2M, has been observed (35). It has been shown that complexation occurs between the riboflavin and the hydrotropic agents cytosine and caffeine, respectively (35). However, in the case of nicotinamide, no evidence for complexation between riboflavin and nicotinamide. 

Some examples of successful commercial selective extractions are the removal of caffeine from coffee or the solubilization of nicotine from tobacco both accomplished on moist matrices to aid in selectively solubilizing the alkaloid component. Selective extraction has been demonstrated for the segregation of essential oil from other lipid components in natural extracts derived from fruits and for the separation of aroma components in cocoa butter from the base oil. Other enrichment SEE schemes that have been reported include the fractionation of carotenoid from leaf protein concentrate [25], the fortification of sterols in seed oils [26], and the isolation of lecithin (phospholipid-containing fraction) from triglycerides [27]. 

Recall trom basic mermodyiiainics that a j,ocess with a negative AG is spontaneous and the product—here, the solvated state—is favored relative to the unsolvated state. The authors of ffie study proposing this alternative approach derived a relationship that exhibited a reasonable correlation with measured values of LogBB. Some values obtained for AG°vv were —5.00 for ethanol (freely water soluble) and 2.08 for hexane for AG°hu the values were —0.16 and —3.45, respectively, for the same compoimds. Caffeine, a water-soluble basic drug, had calculated values of —15.27 and —9.31, respectively. The difference in the AG° values suggests that caffeine is more stable when it is solubilized in water than in a lipophilic medium. In the case of caffeine, the calculated LogBB veilue of 493 compared reasonably well with an experimental value of 40.3. 

Because of the limited solubility of the xanthine derivatives in water, their solubilization by hydrotropes has been the subject of much interest. Such diverse compounds as piperazine [279], sodium salicylate [280], adenosine [281], and diethanolamine [282] have been used to solubilize theophylline. The action of each is presumably due to complex formation. Neish [283] found that caffeine, a xanthine derivative, increased the solubility of a number of aromatic amines, including sulphapyridine, sulphathiazole, and certain dyes. 

The difficulty in using the xanthines in pharmacy is that they have a pharmacological action of their own and limited solubility. However, a number of medicaments contain hydrotropes for their therapeutic effect and not their solubilizing action, such as in aspirin, phenacetin, and caffeine mixtures it is unlikely that the caffeine in this preparation is inactive. 

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