Stability pantothenic acid

Pantothenic acid is relatively labile (185,186). In the dry form, it is hygroscopic and unstable in solution its stability is strongly pH dependent, being greatest at pH 4-5. It is subject to hydrolytic cleavage to pantoic acid and /3-alaninc in more acidic or alkaline solutions. Pantothenic acid is very soluble in water, alcohols, and dioxane, less soluble in diethyl ether and acetone, and insoluble in benzene and chloroform. 

There are some well-described deficiency syndromes, the well-established therapeutic use of vitamin K antagonists as oral anticoagulants and the well-known positive effects of pantothenic acid on skin hydration/moisturization and wound healing, which apparently lacks scientific solid base. Apart from that there are not many studies available on the treatment of dermatological disorders with these vitamins, either systemically or topically. Even less is known about transdermal penetration, stability, and formulation dependencies of possible topical applications. 

The atom efficiency of a kinetic resolution is increased if the starting material is not an ester but a lactone. Indeed, kinetic resolutions of lactones are used on an industrial scale. Fuji/Daiichi Chemicals produces D-pantothenic acid on a multi-ton scale based on such a resolution. D-Pantolactone is hydrolysed at pH 7 by a hydrolase from Fusarium oxysporum yielding D-pantoic acid with an ee of 96% while L-pantoic acid was barely detectable. The immobilized Fusarium oxysporum cells were recycled 180 times and retained 60% of their activity, demonstrating the great stability of this catalytic system [47-50]. 

R)-Pantothenic acid (1) contains two subunits, (R)-pantoic acid and p-alanine. The chemical abstract name is iV-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-p-alanine (11). Only (R)-pantothenic acid is biologically active. Pantothenic acid is unstable under alkaline or acidic conditions, but is stable under neutral conditions. Pantothenic acid is extremely hygroscopic, and there are stability problems associated with the sodium salt of pantothenic acid. The major commercial source of this vitamin is thus the stable calcium salt (3) (calcium pantothenate). 

Panthenol, USP. Panthenol, the racemic alcohol analogue of pantothenic acid, exhibits both qualitatively and quantitatively the vitamin activity of pantothenic acid. It is considerably more stable than pantothenic acid in solutions with pH values of 3 to 5 but of about equal. stability at pH 6 to 8. It appears to be absorbed more readily from the gut. paniculorly in the presence of food-... 

Slightly sol in ether. Natural pH about 9.5. Reasonably stable to usual sterilization time and temp in aq solns adjusted to pH 3.0 -4.0, but long heating causes racemization. Hydrolyzed by alkali and strong acid. Usually more stable than salts of pantothenic acid if pH can be adjusted between 3 and S. For add stability data see Rubin, J. Am. Pharm. Assoc.. ScL Ed. 37, 502 (1948). Aq solns can be stabilized with pantolactone US. pat. 2,898,373 (1959). df-Form, panthenol. 

A similar quantitative analysis of six water-soluble vitamins (B, B2, Bg, C, nicotinamide, and pantothenic acid) in a pharmaceutical formulation using CZE in uncoated fused silica capillaries with UV detection was described by Fotsing et al. (91). Eor the B-group vitamins, a good compromise among resolution, analysis time, and analyte stability was obtained by use of 50 mM borax buffer pH 8.5. A capillary wash with sodium hydroxide was necessary between successive runs to minimize absorption of excipients from the pharmaceutical formulation to the capillary surface, otherwise giving rise to a progressive decrease of the electro-osmotic flow. 

The principal biologically active natural forms of pantothenic acid (vitamin B5), one of the B vitamin complex, are coenzyme A (CoA or CoASH) and acyl-carrier protein (ACP). In solid pharmaceuticals, foods, and feeds, because of simple handling and increased stability, the pantothenic acid sodium and calcium salt are often used as additives. Panthenol is usually used in liquid pharmaceutical preparations and in cosmetics. 

Pantothenic acid is a yellowish viscous oily liquid, which is readily soluble in water, alcohols, and dioxane, slightly soluble in diethyl ether and acetone, and virtually insoluble in benzene and chloroform. The stability of pantothenic acid in aqueous solutions is very pH dependent. It is most stable in slightly acidic medium (pH 4 to 5). Both in acidic and alkaline media it is hydrolytically cleaved to yield pantoic acid and its salts, respectively, and P-alanine. In acidic solutions, pantoic acid spontaneously eliminates one molecule of water, forming R)-2-hydroxy-3,3-dimethyl-4-butanolide (a-hydroxy-P,P-dimethyl-y-butyrolactone), referred to as pantoyl lactone or pantolactone (Fig. 4). 

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... 

At higher ethanol concentrations the intracellular alcohol interferes with membrane organization, increasing its fluidity and permeability to ions and small metabolites and inhibiting transport of nutrients. Especially Ca and Mg ions are able to increase the plasma membrane stability. It has been demonstrated that incorporation of unsaturated fatty acids and/or sterol(s) as well as proteolipids into cellular membrane of yeasts helps to alleviate ethanol tolerance. For the synthesis of the unsaturated fatty acids the presence of traces of oxygen under fermentation conditions is required. Further to Ca and Mg ions, other trace elements such as Co, Cu, Mn and Zn " and vitamins, e.g. pantothenate, thiamine, riboflavin, nicotinic acid, pyridoxine, biotin, folic acid and inositol, are essential for the growth and ethanol production by yeasts. 

The stability of pantothenic add in aqueous solutions depends greatly on the pH value. The vitamin is most stable in weakly acidic (pH 4 5) solutions, but in acidic and alkaline media the amide Hnkage is hydrolysed and pantothenic add yields pantoic add (or its salt) and fl-alanine. The enzyme pantothenase of some baderia specifically cleaves pantothenic add into the same products. In acidic solutions, pantoic acid spontaneously dehydrates to form lactone, (R)-2-hydroxy-3,3-dimethylbutano-4-lactone, which is called pantoyllactone or pantolactone (5-73). Analogously, products of panthenol hydrolysis are pantoic add... 

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