Green Chemistry for the Preparation of Ferrous Ascorbate

Abstract

The present invention relates to an eco-friendly process for the preparation of ferrous Ascorbate, a metal chelate of iron (Fe) in the ferrous state with ascorbic acid, using green chemistry principles. The process is free from harmful chemicals such as halides, sulfates, peroxides, and organic solvents. The process involves the oxidation of Fe(0) to Fe(II) by ascorbic acid and water under controlled conditions of pH (4–5) and temperature (40°C–70°C), resulting in a stable and highly bioavailable ferrous Ascorbate complex. The final product is purified by filtration and isolated via spray drying. The process offers significant environmental benefits, improved safety, and superior product purity, as evidenced by the absence of related impurities, including nitrosamines. The invention is particularly applicable in the production of pharmaceutical-grade ferrous Ascorbate for the treatment of iron deficiency anemia

Specification

Description:FIELD OF THE INVENTION
The present invention relates to an eco-friendly process for the preparation of ferrous Ascorbate, a metal chelate of iron (Fe) in the ferrous state with ascorbic acid. This process is free from harmful chemicals such as halides, sulfates, peroxides, and organic solvents. It utilizes electrolytic iron and ascorbic acid, making the process particularly suitable for producing pharmaceutical-grade iron supplements.
BACKGROUND OF THE INVENTION
Ferrous Ascorbate is a highly bioavailable form of iron used in the treatment of iron deficiency anemia. Ferrous Ascorbate has a better bioavailability, as high as 67%, and utilization of iron when compared to other iron preparations, including sucrosomial iron. Ferrous Ascorbate lacks food interactions and can be administered without regard to food. Ferrous Ascorbate is a stable chelate that does not dissociate in the gastrointestinal tract. Higher absorption of iron from ferrous Ascorbate can be explained by the Ascorbate component that prevents oxidation of the iron to a ferric state. (Ref: Malhotra N, Kriplani A, Pal B, et al. FerrousAscorbate: Current Clinical Place of Therapy in the Managementof Iron Deficiency Anemia. J South Asian Feder Obst Gynae2021;13(3):103-109)
The chemical state of ferrous iron in oral supplements has a distinct advantage over iron in the ferric form. Given the high effectiveness, acceptable tolerability, and low cost of ferrous preparations, these are preferred over ferric preparations of oral iron supplementation.
Ferrous Ascorbate has a quick response as improvement in Hemoglobin can be seen as early as 15 days after the initiation of supplementation with ferrous ascorbate. This complex has good efficacy and excellent safety and tolerability which can be explained by advantages of the chemical state including a better bioavailability and utilization of iron.
Ferrous Ascorbate (FAS) is a metal chelate of iron in the ferrous state with ascorbic acid. The unique chemistry of ferrous ascorbateincludes a high content of iron and its coexistence with ascorbatein the same compound. The Conventional methods for preparing Ferrous Ascorbate involve the use of hazardous chemicals and processes, which pose environmental risks and potential contamination of the final product.
In Prior Art of Indian Patent Application number 650/MUM/2006 discloses the Process for the preparation of Ferrous Ascorbate where Alkali or Alkaline earth metal salt or its hydroxide reacted in aqueous medium with Ferrous or Ferric Salt and followed by treatment with Ascorbic acid to obtain Ferrous Ascorbate. This process involves multi-step chemical reaction where different pH range is required to maintain different reaction and it is so time consuming. The Prior art did not disclose the time taken in every step of chemical reaction. The prior art discloses the pH range of the process is 6 to 9 which imply all phase of compound that is acidic,neutral and basic. The Prior art only discussed ambient temperature but did not disclose the range of temperature involve in the process. In Paragraph 2 of the page 8 of the Complete specification of the prior art disclose the time to obtain Ferrous Ascorbate in solid form that is 2-3 days after preparing of Ferrous Ascorbate in mother liquor.
In Prior Art GB 486,757, the patent discloses the process of preparation of Ferrous Ascorbate wherein ascorbic acid reacted with ferrous chloride then removed the Hydrochloric acid through neutralization with addition of Sodium bicarbonateand still sodium chloride salt formed as product with Ferrous Ascorbate and more purification were required to get desired quality of ferrous Ascorbate.
In Prior art RS50020B and YU33000A discloses the invention of Process for preparing Ferrous Ascorbate where Ferrous Ascorbate obtained from iron powder and ascorbic acid with stirring and heating. The Prior art only disclosed the process of quantitative obtainment of Ferrous Ascorbate through heating and stirring and did not discloseand even silent on the time taken of reaction, pH range and impurities involved in the process.
The disadvantage of existing process for preparation of Ferrous Ascorbate according to prior art as follows
1. Different compound is required as reactant to initiate the process which consequently increase the process time and obtain different by-product with Ferrous Ascorbate and to remove the by-product additional step is required.
2. The prior art is silent on physio-chemical data of the process and product obtained from the process.
3. The prior art lack on robust process filtration and purification.
4. The Prior did not use green chemistry as process to obtain the Ferrous Ascorbate.
Importance of Green Chemistry can be described as follows
The Green chemistry touches upon the latest trend in pharmaceutical chemistry innovations e.g. to use abundantly available natural resources (Iron, water, and oxygen) as a sustainable alternative for doing "Green Chemistry" and /or "Environmentally benign Chemistry". Green Chemistry is a concept that is being embraced around the world to ensure continued economic and environmental prosperity. Modern synthetic methodologies are being developed to preserve performance, while minimising toxicity, use renewable feed stocks and use catalytic and /or recyclable reagents to minimise waste. Green Chemistry is the design and development of chemical products and processes that reduce or eliminate the use of substances harmful to health or environment. In fact, international scientific community has categorically defined following 12 principles of Green Chemistry.
The Twelve (12) principles of Green Chemistry are as follows: -
(a)Prevention- Try not to make waste, then you do not have to clean it up.
(b) Atom economy -The final product should aim to contain all the atoms used in the process.
(c) Less hazardous chemical synthesis- Whenever it is possible, production methods should be designed to make substances that are less toxic to people or the environment.
(d) Designing safer chemicals- Chemical products should be designed to do their job with minimum harm to people or the environment.
(e) Safer Solvents- When making materials try not to use solvents or other unnecessary chemicals. If they are needed then they should not be harmful to the environment in any way.
(f) Design for energy efficiency - The energy needed to carry out a reaction should be minimized to reduce environmental and economic impact. If possible, processes should be carried out at ambient temperatures and pressures.
(g) Use of renewable feed stocks- A raw material should be renewable wherever possible.
(h) Reduce derivatives - Try not to have too many steps in the reaction because this means more reagents are needed and more waste is made.
(i) Catalysis - Reactions that are catalysed are more efficient than uncatalyzed reactions.
(j) Design for degradation - When chemical products are finished with, they should break down into substances that are not toxic and do not stay in the environment.
(k) Real-time analysis for pollution prevention - Methods need to be developed so that harmful products are detected before they are made. (l) Inherently safer chemistry for accident prevention - Substances used in a chemical process should be chosen to minimise the risk of chemical accidents, including explosions and fire.
In fact, USPTO has granted several process Patents recently, which use concept of Green Chemistry. USPTO has granted number of patents during last 2/3 decades where invention involves concepts of green chemistry to create sustainable life, environment and economy. Just to cite few examples, US 4,740,605B2 describes process for preparing 5- Hydroxymethyl furfuraldehyde by exclusive use of water as solvent, whereas US 7,439,388 B2 describes process for converting primary amidoalcohol to amidocarboxylic acids in high yields using water as solvent. Similarly, US 7,741,508 B2 discloses invention for a single step conversion of substituted cinnamic esters without using any organic solvents, whereas US 8,057,682 B2 reports green synthesis of Nano- materials using natural raw materials. A one pot polymerisation method involving "Ring Opening Polymerization" is reported in US 8,143,369 B2, using concepts of green chemistry. Even electronic circuit industry uses concepts of green chemistry to remove unwanted organic substances in US 8,389,455 B2, whereas petroleum industry uses hydro cracking / hydrotreating bio renewable feedstock, with water to produce hydrocarbons in US 9,133,080 B2. Finally, Pharma industry has also used recently water as solvent for preparation of one of the important intermediate of Linagliptin in US 9,522,915 B2.
The present invention addresses the need for an eco-friendly, efficient, and safe process. It employs electrolytic iron and ascorbic acid in a water-based reaction, eliminating the need for harmful solvents or reagents. The process ensures a stable, bioavailable ferrous Ascorbate complex that is free from toxic impurities such as nitrosamines and genotoxic substances.
The Present invention also disclose and detail the impurities such as nitrosamines and genotoxic substances in analytical way to show the robustness of the process of the invention.

OBJECTIIVE OF INVENTION
An object of the Invention is to provide eco-friendly and industrially feasible process for the preparation of ferrous Ascorbate after utilizing the concept of green chemistry
• The use of electrolytic iron, ensuring high purity and safety.
• The oxidation of Fe(0) to Fe(II) by ascorbic acid under mild conditions, producing a stable ferrous Ascorbate complex.
• The optimization of reaction parameters, including pH, stirring speed, and temperature, to prevent degradation of ascorbic acid.
• No use of heat and all stirring happened at room temperature.
• Analysis of invention to show robustness and impurity free process of preparation of Ferrous Ascorbate.
SUMMARY OF THE INVENTION
The present invention describes an eco-friendly process for the preparation of ferrous Ascorbate using electrolytic iron and ascorbic acid in water as the solvent. The reaction is controlled by monitoring pH, stirring speed, and temperature. The process is free from halides, sulfates, peroxides, and organic solvents, making it a green chemistry approach to producing ferrous Ascorbate. The process involves the oxidation of Fe(0) to Fe(II) of Electrolytic iron with use of ascorbic acid and water under controlled conditions of pH (4-5) and temperature (40°C-70°C), resulting in a stable and highly bioavailable ferrous Ascorbate complex. The final product is purified by filtration and isolated via spray drying. The process offers significant environmental benefits, improved safety, and superior product purity, as evidenced by the absence of detectable impurities, including nitrosamines.

Fig 1 shows Chemical structure of Ferrous Ascorbate.
Fig 2 illustrates the synthetic scheme of ferrous Ascorbate preparation.
Fig 3. Genotoxic impurity
Fig.4: Nitrosamine Impurities by FDA
Fig. 5: Mechanism to decompose Nitrosamine
Table 1: Related Impurity Profile
Table 2: Risk Assessment (In line with FDA guideline)
Table 3: Physical properties (Typical values) of Components
Graph 1: Fe(II) Content v/s Batch number to depict the robustness of the manufacturing process and Fe(II) content consistency across batches.
Graph 2: Infrared Spectroscopy
Graph 3: X-ray Diffraction
Graph 4: 1H-Nuclear magnetic resonance spectra
Graph 5: Mass Spectra
Graph 6: High-performance liquid chromatography (HPLC)
Graph 7: Ultraviolet-visible (UV-Vis) spectra
Graph 8: Differential Scanning Calorimeter (DSC)
Graph 9: Thermogravimetric analysis (TGA)







DETAILED DESCRIPTION OF THE INVENTION
The present inventionhas developed eco-friendly, organic solvent free process for the preparation of ferrous Ascorbate (Fig 1). This is halide, sulphate, peroxide free process. The key starting material used in this process is electrolytic iron and ascorbic acid; along with process water as solvent. The novelty involves in this process is the use of electrolytic iron and ascorbic acid. Ascorbic acid oxidize electrolytic iron from Fe(0) to Fe(II) preferably at low pH.


An Ascorbic acid (C6H8O6, H2A) is a water-soluble that can oxidize Fe from 0 state to +2 oxidation state and also act as a chelating agent at low pH. As a two-electron reductant, the redox potential of H2A is about −0.06 V.
So, the chemical equation we can write:
Fe(0) + 2(H2A) Fe(II) + 2A-
The use of electrolytic iron is an overwhelming approach used by the inventors as it has very high purity and assay along with very trace amount of Cobalt, Nickel, Copper, Boron, Chromium, Vanadium and Lead. So, the inventor is very careful about the safety of the finished good at the beginning itself so far, the heavy metals are concerned. The typical properties of electrolytic iron are as follows





Process for the Preparation of Ferrous Ascorbate (Refer to Figure 2)
1. Materials:
o Electrolytic Iron (Fe(0)): High-purity iron with negligible amounts of heavy metals (e.g., cobalt, nickel, copper), ensuring a safe and clean final product.
o Ascorbic Acid (C6H8O6): Acts as both an oxidizing and chelating agent for iron.
o Water: The process solvent, ensuring an environmentally friendly procedure.
2. Reaction Mechanism: The process involves the oxidation of electrolytic iron from Fe(0) to Fe(II) using ascorbic acid in an aqueous medium. Ascorbic acid also serves as a chelating agent for Fe(II), preventing the oxidation to Fe(III) and maintaining iron in its bioavailable ferrous state. The reaction proceeds as:


1. Fe(0)+2(H2A)→Fe(II)+2A−
Where H₂A represents ascorbic acid, and A⁻ is the Ascorbate anion.

Fig. 2: Synthetic Scheme
3. Process Steps (Refer to Figures 2):
o Step 1: Preparation of Solution: Process water is introduced into a clean reactor, followed by the gradual addition of ascorbic acid over a period of 1 to 3 hours with continuous stirring at room temperature. The solution becomes clear when ascorbic acid is fully dissolved.
o Step 2: Addition of Electrolytic Iron: Electrolytic iron is added to the ascorbic acid solution under constant stirring. This is a mild exothermic reaction. At this stage stirring to be continued 1 to 15h, preferably 2 to 13h, more preferably 3 to 10h and more preferably 3 to 9h. The stirring (rotation per min) at this step is a critical process parameter for the preparation of ferrous Ascorbate. The high rotation per min (RPM) leads to the deterioration of ascorbic acid.
The progress of the reaction to be monitored by pH.At the end of the reaction the pH will be in the range of 4 to 5, more preferably 4.2 to 4.8, more preferably inthe range of 4.3 to 4.7.Overreaction will lead the increase of pH which will degrade the desired complex. This mild exothermic reaction raises the temperature to 40°C-70°C.
 Figure 2: Illustrates the synthetic scheme of ferrous Ascorbate preparation, detailing the oxidation of iron and chelation by ascorbic acid.
o Step 4: Filtration and Spray Drying: Once the reaction is complete, the reaction mass is filtered through a sparkler filter to remove impurities. The filtrate is then spray-dried to yield ferrous Ascorbate as a fine, dark violet powder.

Example 1:
In a clean reactor 2500 Lit of process water was added followed by addition of 850 Kg of ascorbic acid under stirring at RT. Stirring was continued till the clear solution obtained. In the same reaction mass 150 Kg of electrolytic iron powder was added slowly under stirring at RTover a period of 8 to 11 h. At this stage the reaction temperature goes up to the range of 40 to 70 deg C. After completion of reaction the pH of the reaction mass becomes 4.3 to 4.7. The reaction mass was filtered through the sparkler filter to remove any unwanted solid impurity. The solution was spray dried to isolate 980 Kg of ferrous Ascorbate.

Impurity Profile Analysis of the Process of preparation of Ferrous Ascorbate
Related Impurity Profile
Table 1 lists the impurities related to the ferrous Ascorbatewhich can be generated from KSM ascorbic acid. The results confirm that the Active Pharmaceutical Ingredient (API) is free from these and other related impurities.



Sl No. Name of the impurity MOA/Control Point % in WBCIL API
1 2-Furaldehyde
CAS :98-01-1
Molecular Formula: C5H4O2 HPLC,
Controlled in KSM ND
2 L-Xylo-hex-2-ulosonic Acid
CAS: 526-98-7
Molecular Formula: C6H10O7 HPLC,
Controlled in KSM ND
3 Methyl D-sorbosonate
CAS: 67776-07-2
Molecular Formula: C7H12O7 HPLC,
Controlled in KSM ND
4 (5R)-5-[(1R)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one
CAS: 89-65-6
Molecular Formula: C6H8O6 HPLC,
Controlled in KSM ND
5 (2R)-2-[(2R)-3,4-Dihydroxy-5-oxo-2,5-dihydrofuran-2-yl]-2-hydroxyacetic acid
CAS: 66757-69-5
Molecular Formula: C6H6O7 HPLC,
Controlled in KSM ND
6 Methyl (2R)-2-[(2R)-3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2-yl]-2-hydroxyacetate
CAS: 122046-79-1
Molecular Formula: C7H8O7 HPLC,
Controlled in KSM ND
Table 1: Related Impurity profile
Genotoxic Impurity Profile:
The present invention ensures that no genotoxic impurities are formed during the process, as no reagents with genotoxic potential are used. Structural elements that could lead to genotoxic impurities are not present in the final product.
Genotoxic impurities can occur in drug products based on the manufacturing of the API, degradation of the API, or in some cases, from the excipients. The source of genotoxic impurities in the API and drug product generally is the API manufacturing process, including starting materials and reagents. Reagents used in API synthesis are often highly reactive, and genotoxic impurities can result from leftover reagents carried through the manufacturing process, by-products of the chemical transformations, or the subsequent degradation/interactions of the API. Although rare, genotoxic impurities occasionally form in the drug product as a result of interaction of the API with excipients.
The presence of following structural part (in totality or by parts) can lead to the formation of Genotoxic impurity in Ferrous Ascorbate

Fig. 3: Genotoxic impurity
In present invention, as the ferrous Ascorbate manufacturing process does not involve use any reagent having the above structural part hence our API is free from Genotoxic impurity.

Nitrosamine Impurity
The term nitrosamine describes a class of compounds having the chemical structure of a nitroso group bonded to an amine (R1N(-R2)-N=O), as shown in the Fig.4. The compounds can form by a nitrosating reaction between amines (secondary, tertiary, or quaternary amines) and nitrous acid (nitrite salts under acidic conditions).
Representative Reaction to Form Nitrosamines:
Food and Drug Authority has identified seven nitrosamine impurities that theoretically could be present in drug products: NDMA, N-nitrosodiethylamine (NDEA), N-nitroso-N-methyl-4-aminobutanoic acid (NMBA), N-nitrosoisopropylethyl amine (NIPEA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodibutylamine (NDBA), and N-nitrosomethylphenylamine (NMPA). Five of them (NDMA, NDEA, NMBA, NIPEA, and NMPA) have actually been detected in drug some substances or drug products. As in our process any amine, nitric acid, nitrate, nitrite, azide, 2nd crop of the product, recovered solvent i.e., waterare not used, hence we declare thar our APIs are free any nitrosamine impurities.


Fig.4: Nitrosamine Impurities by FDA


The risk of nitrosamine formation was evaluated and documented in Table 2. As no nitrites, nitrates, amines, or related sources are used in the process, the risk of nitrosamine formation is negligible.


Risk Factors Assessment
Are nitrites (NO2-), nitrous acid, amine, nitrates (NO3-), nitric acid, or azides (N3-) or their sources present in any excipients (e.g., microcrystalline cellulose), processing aids (e.g., water, nitrogen)?
No
Are peroxides present in any of the excipients, processing aids?
Are nitrites (NO2-), nitrous acid, nitrates (NO3-), nitric acid, or azides (N3-) or their sources present in packaging components (including ink, and materials permeability factors)?
Are any components containing/potentially containing nitrites present together in solution or in suspension during processing?
Are nitrites (NO2-), nitrous acid, nitrates (NO3-), amine, nitric acid, or azides (N3-) or their sources present in chemically synthesized APIs? No
Based on the structure of drug substance, is there any possibility of formation of nitroso compounds by interaction of drug substance? No
Based on the structure of excipients/KSM, is there any possibility of formation of nitroso compounds by interaction between excipients/KSM?
Are any components containing/potentially containing nitrites and amines maintained together at elevated temperatures (about 200 deg C, e.g., during drying, coating stages, autoclaving, etc.)? No
Do solvents or any other process materials undergo recycling/recovery? No
In the manufacturing process of the drug product, are any of the solvents, spent solvents, or process materials treated prior to or during recovery (in-house or by a third party) such that the treatment could lead to formation of amines or nitrosonium ions that could be introduced back into the process through the recovered solvents?
Are the recovered materials, if any, dedicated to the process? No recovered material is used in the process
Is there a potential for nitrosamine impurity formation during the finished product manufacturing, through degradation and by-products (i.e., if certain excipients, APIs, or packaging components containing sources of amines and nitrite are used together)?
No
Are there nitrosonium ions (degradation and by-products) likely to come into contact with each other either in the same processing step or through carryover into subsequent processing steps?
Is there any potential of nitrosamine formation during storage throughout the finished product's shelf life? No
Is chloramine used as part of water treatment, used for cleaning, or as part of the production process? No
Have the cleaning solvents/cleaning agents used been assessed for nitrosamine or nitrosamine precursor risk? Only the purified water is used as cleaning solvent.
Manufacturing of oral drug product typically involves (e.g., solid oral dry, wet, or direct compression) manufacturing processes utilizing specific equipment. Do any of the processes contribute toward formation of N-Nitrosamines? No
Are sartan drug products manufactured in the same facility? No
Manufacturing equipment design. Reviewed the equipment and it meets the current GMP and validation/qualification standards. Confirm continued suitability to the manufacturing and cleaning process.
Manufacturing equipment material of construction. The adequacy of the contact surfaces and their suitability respect to the qualified cleaning method, cleaning water used, and frequency verified.
Are chemicals such as sodium azide or sodium nitrite, which are primary sources of nitrosamine impurity, used in the facility? No
Table 2: Nitrosamine Risk Assessment (in line with FDA guidelines)

The above review is expected to provide us high level of confidence for the absence of Nitrosamine impurities in present invention. For the sake of argument, if we consider traces of nitrosamine impurities formed due to environmental contamination it undergoes decomposition under acid catalysed reaction condition of Fe(II)/Ascorbic acid; in the following mechanistic pathway

Fig. 5: Mechanism to decompose Nitrosamine
From the above logic, it has been established that there is no nitrosamine impurity in present invention of ferrous Ascorbate.


Robustness of the Manufacturing Process
The present invention is controlled by Quality by Design (QbD) and Design of Experiment (DoE). The following graph is self-explanatory about the robustness of the process. The Fe(II) content of the five batches are very consistent.
Ferrous content with respect to different batches of Ferrous Ascorbate:

Graph 1: Fe(II) content v/s Batch number
The X-axis indicates batch number and Y axis indicates Fe(II) content.
Physico-chemical Data:
Description Fine dark violet powder
Solubility Freely soluble in water and DMSO. Insoluble in organic solvent.
pH (in 1% w/v content) About 6.68
Ferrous content (ODB) 15.38 w/w
Ascorbic acid content 78.10 w/w
Table 3: Physical Properties (Typical values)
Typical Value of Untapped Density: 0.19g/cc.
Typical Value of Tapped Density:0.25 g/cc.

Infrared Spectroscopy (IR)

Graph 2: Infrared Spectroscopy
The Interpretation is follows: Wave number in cm-1.
Wave number (about) Assignment
3370 -OH
1710, 1610 -C=O, C=C
1100,1050 -C-O-C
X-ray Diffraction (XRD)

Graph 3: X-ray Diffraction
The X-ray diffraction of the present invention is amorphous in nature
H-NMR
The 1H-NMR (Nuclear magnetic resonance) shows the following spectral pattern:

Graph 4: H-Nuclear magnetic resonance
The spectra represent the following interpretation:






Mass Spectra:
The base peak at m/z 261 stands for fragment [Ascorbic Acid + H++ 2.Fe - CO]+.

Graph 5: Mass Spectra
HPLC:
The HPLC purity of ascorbic acid is about 100% which indicates the absence of relative impurities as mentioned in the Table-1.

Graph 6: High-performance liquid chromatography (HPLC)
The HPLC of corresponding Ferrous Ascorbate shows the substantial purity of the product.

UV-Vis:
Absorbance maxima were found at λmaxof 244 nm in 0.1 (N) HCl solution. The λmax of 244 nm indicates presence of the uncoordinated Ascorbate anion in solution.

Graph 7: Ultraviolet-visible (UV-Vis)

Differential Scanning Calorimeter (DSC):
The DSC shows crystallization temperature at 236.57 deg C (endotherm), which indicates the amorphous ferrous Ascorbate converts to crystalline ferrous Ascorbate at about 236.57 deg C (normalized enthalpy 307.81 J/g).The exotherm at about 118 deg C is phase transition temperature. The absence of endothermic peak in the thermogram at 193°C, which was considered as the fusion temperature of ascorbic acid indicates the absence of free ascorbic acid.

Graph 8: Differential Scanning Calorimeter (DSC)


TGA:
As ferrous Ascorbate was subjected to heat and found that Ferrous Ascorbate to be stable. As temperature increased to 105°C, decrease in weight observed only 6.26% due to loss of moisture, whichwas used for synthesis of ferrous Ascorbate. After that, degradation was observed at about 240 deg C.

Graph 9: Thermo gravimetric analysis (TGA)











, Claims:We Claim
1. A process for the preparation of ferrous Ascorbate, wherein electrolytic iron is oxidized from Fe(0) to Fe(II) by ascorbic acid and water as a solvent, under conditions free from halides, sulfates, peroxides, and organic solvents with stirring at room temperature (RT) using principle of green chemistry.
2. The process as claimed in claim 1, wherein electrolytic iron is oxidized from Fe(0) to Fe(II) using ascorbic acid as chelating agent at low pH and redox potential -0.06 V.
3. The process as claimed in claim 1, wherein addition of process water with ascorbic acid under stirring over a period of 1 to 3 hours to get a clear solution.
4. The process as claimed in claim 1, wherein the addition of electrolytic iron as per claim 2 and resulting solution as per claim 3 stirring at room temperature continued to 1 to 15 hours.
5. The process as claimed in claim 1, wherein the pH of the reaction mass as per claim 4 is maintained between 4 and 5 as the endpoint of the reaction.
6. The process as claimed in claim 1, wherein the reaction as per claim 4the temperature goes between 40°C and 70°C with stirring.
7. The process as claimed in claim 1, wherein stirring speed is controlled to prevent degradation of ascorbic acid, with stirring continued for 1 to 15 hours.
8. The process as claimed in claim 1, wherein the final product is isolated by spray drying after filtration.
9. The process as claimed in claim 1, wherein the final product is free from chloride.
10. Ferrous Ascorbate prepared by the process claimed in any of the preceding claims 1-9, having high bioavailability, stability, and purity, free from hazardous impurities and devoid of OVI including other halides, sulfates, and nitrosamines which is present in the preparation of Ferrous Ascorbate available in the market.

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