Stability riboflavin

Other mediators which have been used in combination with diaphorase for the regeneration of NAD+ are riboflavin and Vitamin K3, which is 2,3-dimethyl-1,4-naphthoquinone. However, especially riboflavin is not stable enough for synthetic applications [40]. Better stability is exhibited by phenanthrolindiones as mediators. In combination with diaphorase, Ohshiro [41] showed the indirect electrochemical oxidation of cyclohexanol to cyclohexanone using the NAD+ dependent HLADH with a turnover frequency of two per hour. For an effective enzymatic synthesis, this turnover frequency, however, would be too small. In our own studies, we were able to accelerate the NAD(P)+ regeneration considerably by lowering the electron density within the... 

Peroxide formation has also been observed in multivitamin solutions for parenteral nutrition. Lavoie and co-workers [30] have studied the action of light, air, and composition on the stability of multivitamin formulations, and also total parenteral nutrition (TPN) admixtures containing and not containing vitamins and fatty acids. They analyzed the generation of peroxide in multivitamin solutions and in TPN for adults and neonates. The analysis of multivitamin solutions for enteral use revealed the presence of peroxides at the initial opening of the bottle. The levels were higher in Poly-Vi-Sol (vitamin A, Vitamin D, and vitamin C, vitamin Bb riboflavin, and... 

The stability of some vitamins is influenced by aw. In general, the stability of retinol (vitamin A), thiamin (vitamin Bj) and riboflavin (vitamin B2) decreases with increasing aw. At low av (below 0.40), metal ions do not have a catalytic effect on the destruction of ascorbic acid. The rate of loss of ascorbic acid increases exponentially as aw increases. The photodegradation of riboflavin (Chapter 6) is also accelerated by increasing aw. 

Flavin coenzymes are usually bound tightly to proteins and cycle between reduced and oxidized states while attached to the same protein molecule. In a free unbound coenzyme the redox potential is determined by the structures of the oxidized and reduced forms of the couple. Both riboflavin and the pyridine nucleotides contain aromatic ring systems that are stabilized by resonance. Part of this resonance stabilization is lost upon reduction. The value of E° depends in part upon the varying amounts of resonance in the oxidized and reduced forms. The structures of the coenzymes have apparently evolved to provide values of E° appropriate for their biological functions. 

This material is less bitter than riboflavin its water stability is also greater than that of the unmodified material. It is normally only encountered as a pure synthetic substance. Like riboflavin, it is used on panned products. 

There is some evidence that riboflavin status affects the stability of the thermolab ile variant of methylene tetrahydrofolate reductase (Section 10.3.2.1), and that supplements of riboflavin may lower plasma homocysteine (Section 10.3.4.2) in people who are homozygous for the variant enzyme (McNulty et al., 2002). 

Flavoenzymes are widespread in nature and are involved in many different chemical reactions. Flavoenzymes contain a flavin mononucleotide (FMN) or more often a flavin adenine dinucleotide (FAD) as redox-active prosthetic group. Both cofactors are synthesized from riboflavin (vitamin B2) by microorganisms and plants. Most flavoenzymes bind the flavin cofactor in a noncovalent mode (1). In about 10% of aU flavoenzymes, the isoalloxazine ring of the flavin is covalently linked to the polypeptide chain (2, 3). Covalent binding increases the redox potential of the flavin and its oxidation power, but it may also be beneficial for protein stability, especially in flavin-deficient environments. 

Asker AF, Habib MJ. Effect of certain stabilizers on the photobleaching of riboflavin solutions. Drug Dev Ind Pharm 1990 16(1) 149-156. 

The extent of photodegradation of riboflavin is not evident by either visual or spectrophotometric means (49). These results clearly demonstrate that these techniques, though rapid and easy to perform, are not appropriate in all circumstances and that good, validated, stability-indicating analytical techniques should be used to quantitatively determine the extent of photodecomposition. 

Table 7 Effect of Various Stabilizers on the Photobleaching of Riboflavin Solution...

As a coenzyme component in tissue oxidation—reduction and respiration, riboflavin is distributed in some degree in virtually all naturally occurring foods. Liver, heart, kidney, milk, eggs, lean meats, malted barley, and fresh leafy vegetables are particulady good sources of riboflavin (see Table 1). It does not seem to have long stability in food products (8). 

Many vitamins are quite stable under normal processing conditions and present little or no stability problems in finished pharmaceutical products. These include biotin, niacin, niacinamide, pyridoxine, riboflavin, and a-tocopheryl acetate. Others that can present problems are ascorbic acid, calciferol, calcium pantothenate, cyanocobalamin, fola-cin, and retinyl esters. Overages above label claim are customarily added to vitamin formulations as a means of maintaining the claimed level of each vitamin for the expected shelf life of the products. The percent overage for a particular vitamin such as L-ascorbic acid will vary... 

Measurements made during the first 50 msec after passing the maximum and in the presence of either erythrocuprein or cytochrome c show an accelerated decay of the Oi- From Fig. 24 it can further be concluded that the superoxide anion is present in much higher concentrations at pH. 10.6 which is probably due to the higher stability of Oi- at elevated pH values (193). On the other hand Oi- is involved in autocatalytic reoxidation of reduced flavins, as demonstrated in stopped-flow studies. For example, in the presence of 0.1 erythrocuprein the reoxidation of tetra-acetyl riboflavin by O2 was diminished by a factor of 4 (151). 

Several vitamins are known to be photolabile, and the photochemical stability of these compounds is influenced by TPN composition. The photochemical stability depends on composition of the amino acid solutions as well as the presence of lipids in the preparations (i.e., the formation of emulsions). Photochemical decomposition of the hpophihc vitamin A is reduced in admixtures containing lipids, possibly due to diffusion of the vitamin into the lipophilic phase. On the other hand, the hydrophilic vitamin riboflavin is protected by emulsification, probably because the opaque emulsion will reduce the optical transmission of the preparation to some extent (Smith et al., 1988). However, emulsification protects neither the water-soluble vitamin C nor the lipohilic vitamins A and K1 from photochemical degradation, which illustrates the complexity of photochemical reactions in heterogeneous media (Smith et. al., 1988 Billionrey et al., 1993). 

Cyclodextrins will easily form inclusion complexes with several lipophilic drugs, leading to improved pharmaceutical and chemical properties such as solubility, chemical reactivity, pKa value, diffusion properties, and spectral properties (Bortolus and Monti, 1996). As a result of the complexation, photochemical stability of the included drug may be improved or reduced (Ammar and El-Nahhas, 1995 Chen et al., 1996 Mielcarek, 1996). Inclusion of riboflavin into y-cyclodextrins increases photochemical stability sixfold (Loukas et al., 1995). Factors essential for the resulting... 

Multicomponent liposomes reveal optimal UV protection in combination with me y-cyclodextrin complex of me vitamin present in me aqueous phases and lipid-soluble protectors (UV absorbers and antioxidants) present in me lipid phases (Loukas et al., 1995). The experimental photochemical half-life of riboflavin can be increased up to 266-fold by these complex liposome formulations. The liposomal composition is also important for me stabilizing effect obtained as incorporation of riboflavin into neutral and negatively charged liposomes increases photochemical stability, while association with positively charged liposomes leads to a decreased photochemical stability (Habib and Asker, 1991). Incorporation of retinol into multilamellar liposomes is demonstrated to extend the shelf-life of retinol under various conditions of pH, temperature, and light exposure (Lee et al., 2002). 

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