Stability of Vitamin B12—Folic Acid Parenteral Solutions

Taub, Abraham; Lieberman, Herbert A.

doi:10.1002/jps.3030420402

Cited by 15 publications

(13 citation statements)

References 5 publications

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“…In addition, the folic acid-containing particles were >0.8 µm in size, so this method would also be unfeasible for cell culture applications due to the folic acid-containing particles being filtered out of solution during the sterilization step (CCM is typically sterilized via filtration through 0.2 µm sterilization filters before use in culture). Small molecules shown to provide higher folic acid concentrations at lower pH values include nicotinamide (Taub & Lieberman, 1953) and higher viscosity liquids, such as syrups and propylene glycol, though the percentage of these liquid additives (usually >20%), while fine in pharmaceutical preparations, are generally too high to be considered applicable for CCM (Biamonte & Schneller, 1951 converted between multiple active forms intracellularly. It does not naturally (i.e., in cells) exist in the cyano form but rather gains the cyano group only during the process of isolating the vitamin from cells (Reddy, 1999).…”

Section: Stabilizationmentioning

confidence: 99%

“…These supersaturated solutions are stabilized to a point (determined by the thermodynamics of the compound and the solvent environment) but upon reaching the boundaries of saturation for the compound at a given pH, the compound will precipitate out of solution. Acidifying below about pH 6 results in folic acid undergoing either degradation and/or precipitation (Biamonte & Schneller, ; Taub & Lieberman, ).…”

Section: Folic Acidmentioning

confidence: 99%

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Vitamins in cell culture media: Stability and stabilization strategies

Schnellbaecher

Binder

Bellmaine

et al. 2019

Biotech & Bioengineering

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Nowadays, chemically defined cell culture media (CCM) have replaced serum‐ and hydrolysate‐based media that rely on complex ingredients, such as yeast extracts or peptones. Benefits include a significantly lower lot‐to‐lot variability, more efficient manufacturing by reduction to essential components, and the ability to exclude components that may negatively influence growth, viability, or productivity. Even though current chemically defined CCMs provide an excellent basis for various mammalian biotechnological processes, vitamin instabilities are known to be a key factor contributing to the variabilities still present in liquid CCM as well as to short storage times. In this review, the chemical degradation pathways and products for the most relevant vitamins for CCM will be discussed, with a focus on the effects of light, oxygen, heat, and other CCM compounds. Different approaches to stabilize vitamins in solution, such as replacement with analogs, encapsulation, or the addition of stabilizing compounds will also be reviewed. While these vitamins and vitamin stabilization approaches are presented here as particular for CCM, the application of these concepts can also be considered relevant for pharmaceutical, medical, and food supplement purposes. More precise knowledge regarding vitamin instabilities will contribute to stabilize future formulations and thus decrease residual lot‐to‐lot variability.

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Section: Stabilizationmentioning

confidence: 99%

Section: Folic Acidmentioning

confidence: 99%

Vitamins in cell culture media: Stability and stabilization strategies

Schnellbaecher

Binder

Bellmaine

et al. 2019

Biotech & Bioengineering

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“…Also, the ionic strength of buffer solutions helps to solubilize FA in PBS buffer (pH 7). [33] Thus, FA is insoluble below pH 7a nd that is the reason we have used water at low pH ( % 4) to produce the gel. FA powder is highly soluble in PBS (pH 7).…”

Section: Methodsmentioning

confidence: 99%

“…FA powder is highly soluble in PBS (pH 7). [33] FA powder (10 mg) was dissolved in PBS (1 mL, pH 7). Afterward, GdL (4 mol equivalent of FA powder) was added to the homogeneous FA solution and was mixed homogeneously.H ere, GdL undergoes hydrolysis and yields gluconic acid, providing am eans to gradually adjust the solution pH of small molecule hydrogelators, and the remarkable result of this approach is the onset of self-assembly and hydrogelation of FA.T he homogeneous solution was kept undisturbed at RT (30 8C) for 3h,a fter which it turns into ay ellowish gel.…”

Section: Methodsmentioning

confidence: 99%

Injectable Hydrogel of Vitamin B₉ for the Controlled Release of Both Hydrophilic and Hydrophobic Anticancer Drugs

et al. 2018

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Folic acid (FA), vitamin B , is a good receptor of drugs triggering cellular uptake via endocytosis. FA is sparingly soluble in water. Herein, a new approach for the formation of FA hydrogel by the hydrolysis of glucono-δ-lactone in PBS buffer under physiological conditions has been reported. The gel has a fibrillar network morphology attributable to intermolecular H-bonding and π-stacking interactions. The thixotropic property of the gel is used for the encapsulation of both hydrophilic [doxorubicin (DOX)] and hydrophobic [camptothecin (CPT)] drugs. The loading of DOX and CPT into the gel is attributed to the H-bonding interaction between FA and drugs. The release of DOX is sustainable at pH 4 and 7, and the Peppas model indicates that at pH 7 the diffusion of the drug is Fickian but it is non-Fickian at pH 4. The release of CPT is monitored by fluorescence spectroscopy, which also corroborates the combined release of both drugs. The metylthiazolyldiphenyltetrazolium bromide assay of FA hydrogel demonstrates nontoxic behavior and that the cytotoxicity of the DOX-loaded FA hydrogel is higher than that of pure DOX, with a minimal effect on normal cells.

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“…FA is a crystalline drug, very slightly soluble in water (1.6 mg L −1 ) at 25 °C [13] and its solubility varies with temperature and pH media. [45][46][47] Hence, poorly absorbed from the gastrointestinal (GI) tract when used alone. [48,49] Therefore, to enhance the solubility of FA in water constitutes one of our important objectives.…”

Section: Solubility Enhancement Of Fa In Watermentioning

confidence: 99%

Poly(2-hydroxyethylmethacrylate-graft-folic acid), synthesis, solubility enhancement, and release dynamic of folic acid

Beagan

Aouak

AlJuhaiman

et al. 2016

Designed Monomers and Polymers

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A series of poly (2-hydroxyethylmethacrylate-graft-folic acid) (FAHEMA) systems are synthesized by grafting of folic acid (FA) into poly (2-hydroxyethylmethacrylate) via an esterification reaction. The structure of these copolymers is confirmed by NMR and CHN analyses. The thermal behavior of these materials is characterized by DSC and TGA analyses. The surface morphology of FAHEMA films before and after the release process is examined by the SEM method. The cumulative FA released in different pH media from FAHEMA materials occurred via a retro-esterification reaction at body temperature during 72 h in which the influence of the swelling degree of PHEMA, the FA content and pH media on the dynamic release is widely investigated. The results obtained revealed that the solubility of FA in water deduced from the release process is widely improved compared with literature reports. It is also revealed that the diffusion of water in different pH media through the PHEMA matrix and that of FA through FAHEMA materials perfectly obeyed the Fickian models. It was deduced from the kinetic study that the release performance is obtained with the copolymers containing initially 10 and 20 wt% of FA contents.

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Stability of Vitamin B12—Folic Acid Parenteral Solutions

Cited by 15 publications

References 5 publications

Vitamins in cell culture media: Stability and stabilization strategies

Vitamins in cell culture media: Stability and stabilization strategies

Injectable Hydrogel of Vitamin B₉ for the Controlled Release of Both Hydrophilic and Hydrophobic Anticancer Drugs

Poly(2-hydroxyethylmethacrylate-graft-folic acid), synthesis, solubility enhancement, and release dynamic of folic acid

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Stability of Vitamin B12—Folic Acid Parenteral Solutions

Cited by 15 publications

References 5 publications

Vitamins in cell culture media: Stability and stabilization strategies

Vitamins in cell culture media: Stability and stabilization strategies

Injectable Hydrogel of Vitamin B9 for the Controlled Release of Both Hydrophilic and Hydrophobic Anticancer Drugs

Poly(2-hydroxyethylmethacrylate-graft-folic acid), synthesis, solubility enhancement, and release dynamic of folic acid

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Product

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Injectable Hydrogel of Vitamin B₉ for the Controlled Release of Both Hydrophilic and Hydrophobic Anticancer Drugs