Description:FIELD OF THE INVENTION:
The invention pertains to the chemical synthesis of L-Ornithine L-Aspartate (LOLA), focusing on an innovative, greener, single-step in-situ process, yielding a stable, non-hygroscopic, high-purity compound, applicable broadly in human and veterinary medicine, as well as agriculture.
BACKGROUND OF THE INVENTION:
LOLA consists of L-ornithine and L-aspartate, both of which have polar functional groups (amino and carboxyl). These groups form hydrogen bonds with water molecules, leading to moisture absorption. LOLA is a zwitterionic compound, which enhances its ability to attract water molecules. Due to hygroscopicity of LOLA impact on its medicinal activities as well as stability.
L-Ornithine L-Aspartate (LOLA) is recognized for ammonia detoxification and hepatic support, widely employed to treat hepatic encephalopathy (HE) and hyperammonemia in various liver diseases.
L-Ornithine L-Aspartate (LOLA) is a multifunctional compound that plays a crucial role in ammonia detoxification, liver health support, and metabolic regulation. Its applications extend beyond human healthcare to veterinary medicine and agriculture, making it a valuable compound across the following multiple sectors which is detailed below in Table 1-

Compounds Human health use Animal health use Agriculture use
L-ornithine L-Aspartate (LOLA) Supports liver function, reduces ammonia levels, treats hepatic encephalopathy, improves fatigue recovery. Used in veterinary medicine for liver health, reduces ammonia toxicity, supports metabolic functions. Used as a feed additive to improve animal health, supports nitrogen metabolism, enhances growth.
Table 1: Application of LOLA
In several literatures shows, LOLA is made from L-Ornithine hydrochloride, L-Ornithine acetate, L-Ornithine vitriol, L-Arginine hydrochloride etc. In these processes, ammonium hydroxide is used for controlling pH of the solution. As a result, LOLAcontains higher quantities of toxic ammonium, chloride and sulphate. Therefore, the need arises for a synthesis route free of these contaminants, offering improved safety and efficacy.
In prior art CN110627671 tilted ‘Industrial preparation method of ornithine aspartate’ where L-arginine with aspartic acid used and activator which is metal chloride of MgCl2 or FeCl3 and the process also used solvent like methanol, ethanol or isopropanol for crystallization and obtaining ornithine aspartate.
In prior art GB1080599 tiled ‘Improvements in and relating to l-ornithine l-aspartate’ where L-Ornithine L-aspartate is prepared by reacting L-ornithine with L-aspartic acid or an acid addition salt of L-ornithine with a metal salt of L-aspartic acid in the presence of water. In this process temperature range is too high (60-700 0C). In this process there are additional step to remove metal salt. In this process organic solvent like methanol, ethanol or acetone. The prior art process heating of the solution at least 600 0C for which required lots of energy.
In prior art CN101843587 titled ‘Method for preparing ornithine aspartate powder injection for injection’ where removal and filtration of barium ionfrom L-ornithine very complex and the process used organic solvent for crystallization and also used active carbon for decoloration and again used ethanol for crystallization and obtainment of ornithine aspartate powder. Removal and filtration of carbon again additional process of prior art through microporous membrane.
The existing prior art where synthesis method involves multiple reaction steps with low atom economy, resulting in excessive waste generation and high production costs. The existing prior art also silent on impurities from and during the preparation of L-Ornithine L-Aspartate.
OBJECTIVE OF THE PRESENT INVENTION:
The primary objective of the present invention is to develop an efficient, greener, and cost-effective single-step synthesis method for producing stable, non-hygroscopic L-Ornithine L-Aspartate, devoid of toxic impurities such as ammonium, chloride, sulphate, and nitrosamines. The LOLA is suitable for widespread medical, veterinary, and agricultural applications.
FEATURES OF THE PRESENT INVENTION:
1. Greener and single-step synthetic process using safer reagents (L-Arginine free base, barium hydroxide octahydrate, and sodium bicarbonate).
2. Produces a stable, non-hygroscopic, high-purity L-Ornithine L-Aspartate.
3. Free from toxic impurities like ammonium, chloride, sulphate, and nitrosamines.
4. Enhanced yield and purity compared to traditional synthetic methods.
5. Process scalability and suitable for industrial applications.
6. Recyclable by-product, barium carbonate, reducing waste and improving sustainability.
7. Robust and reproducible process ensuring consistent quality.
The present invention process, L-arginine free base and sodium hydrogen carbonate (sodium bicarbonate) are used. So, this process is efficiently controlled the toxic ammonium as well as chloride and sulphate content in LOLA.
The present invention optimize reaction pathways by employing green chemistry principles, using alternative solvent water, and integrating catalytic processes to improve yield.
The present invention process to ensure that the L-Ornithine L-Aspartate is free from impurities or by products that could compromise its safety and efficacy.
The present invention is to manufacture stable, free from toxic elements and non-hygroscopic L-ornithine L-aspartate with cost effective, higher yield, robust and greener in-situ manufacturing process.
SUMMARY OF THE INVENTION
The present invention discloses a single-step greener synthetic method involving hydrolysis of L-Arginine free base using Barium Hydroxide octahydrate, subsequent removal of barium using sodium bicarbonate, reaction with L-aspartic acid, and final spray drying. The process yields stable, non-hygroscopic, high-purity LOLA, free from ammonium, chloride, sulphate, and nitrosamine impurities.
The present invention involves dissolving barium hydroxide octahydrate in water, adding L-arginine, maintaining the reaction at ≤80°C for ≤20 hours. The mixture is cooled, sodium bicarbonate is introduced, precipitating barium carbonate which is filtered. Subsequently, L-aspartic acid is added at ≤30°C for ≤10 hours, and spray dried to higher yield of LOLA.
DESCRIPTION OF DRAWINGS:
• Fig. 1: Chemical Structure of LOLA
• Fig. 2: Reaction Scheme
• Fig. 3: HPLC of L-Arginine
• Fig. 4: HPLC of L-Aspartic Acid
• Fig. 5: HPLC of LOLA
• Fig. 6: Representative Reaction to form Nitrosamine
• Fig. 7: List of Nitrosamine Impurities
• Fig. 8: Proposed mechanism of decomposition of Nitrosamine impurities
• Fig. 9: Infrared Absorption (IR) of LOLA
• Fig. 10: H-NMR spectra of LOLA
• Fig. 11: HRMS of LOLA
• Fig. 12: DSC of LOLA
• Fig. 13: TGA of LOLA
DETAILED DESCRIPTION:
Chemical Composition and Applications:
LOLA is a zwitterionic salt comprising L-Ornithine and L-Aspartic acid, known for its health benefits in detoxifying ammonia and supporting liver functions. Applications span from clinical therapeutics in humans to veterinary applications and agricultural uses, enhancing liver health, metabolic function, muscle recovery, and crop yield.
Physicochemical Properties:
• Molecular Formula: C9H19N3O6
• Molecular Weight: 265.26
• CAS Number: [3230-94-2]

Fig. 1: Chemical Structure of L-Ornithine L-Aspartate (LOLA)
L-Ornithine L-Aspartate (LOLA) is a stable salt formed by combining the amino acids L-ornithine and L-aspartic acid. LOLA is a molecular complex rather than a covalent compound. It is formed by the ionic interaction between L-ornithine (C₅H₁₂N₂O₂) and L-aspartic acid (C₄H₇NO₄), where the amino groups of L-ornithine interact with the carboxyl groups of L-aspartic acid.
SYNTHETIC METHOD
The preparation of L-ornithine L-aspartate is an one-step in-situ process as mentioned in Fig. 2. The step is involved, addition of L-Arginine and barium hydroxide octahydrate in water followed by addition of sodium bicarbonate for formation of barium carbonate and L-ornithine free base. Solid barium carbonate is filtered. L-aspartic acid is added in the reaction mixture and stirred at room temperature followed by spray drying for final desired product.
Barium hydroxide octahydrate is added in water maximum (1:20) ratio and the reaction mixture is stirred at maximum 80⁰C for complete dissolution. Mole ratio of Barium hydroxide octahydrate and L-arginine is varied in the reaction mixture 0.3 to 6.0. Reaction mass is stirred at maximum 80⁰C for maximum 20 hrs. The reaction mass is cooled at below 30⁰C. Sodium hydrogen carbonate is added maximum 1.5:1 ratio by mole with respect to barium hydroxide octahydrate and the reaction mass is stirred at below 30⁰C for maximum10 hrs. Barium carbonate will be formed and the solid barium carbonate is removed from the reaction mixture by filtration. L-Aspartic acid is added maximum 3:3 mole ratio with respect to input L-Arginine.The reaction mixture is stirred at below 30⁰C for maximum 10 hrs. Finally, the reaction mass is spray dried to get the desired non-hygroscopic, industrially scalable and stable L-ornithine L-aspartate with higher yield.
The synthesis of L-Ornithine L-Aspartate (LOLA) from L-Arginine involves, Hydrolysis of L-arginine free base using barium hydroxide octahydrate under alkaline conditions leads to the cleavage of the guanidino side chain, resulting in the formation of L-ornithine free base, ammonia and carbondioxide. Barium is removed by the reaction of sodium bicarbonate as barium carbonate followed by filtration. L-aspartic acid is added in the reaction mass to form L-ornithine L-aspartate. The solid material is collected by spray drying.
The present invention where process involves:
• Dissolving barium hydroxide octahydrate (1:20 ratio by weight) in water and heating ≤80°C.
• Adding L-Arginine, stirring ≤80°C for ≤20 hrs.
• Cooling to ≤30°C, adding sodium bicarbonate (1.5:1 mole ratio with respect to barium hydroxide octahydrate).
• Filtering barium carbonate, adding L-aspartic acid (maximum 3:3 mole ratio to L-Arginine), stirring ≤30°C for ≤10 hrs.
• Spray drying final product to obtain stable LOLA.

Fig.2: Reaction scheme
Recycling procedure to obtain Barium Hydroxide from residual Barium Carbonate
Barium carbonate in water is heated at below 80⁰C under stirring. Calcium hydroxide is added stoichiometric or slightly excess slowly under stirring. The mixture is stirred at 70 ⁰C -80 ⁰C for 5-6 hrs. Calcium carbonate is formed which is filtered out (can be reused after drying), the filtrate is cooled slowly and add seed of barium hydroxide octahydrate (if required) during crystallization. The solid is filtered and dried for further using.
Working example:
Method for preparation of L-Ornithine L-Aspartate:
189 Kg barium hydroxide octahydrate is added in about 780 L water. The mixture is heated at 70-78 ⁰C for complete dissolution of barium hydroxide. 52 kg L-arginine is added in the reaction mass and stirred at 70-78 ⁰C for about 5 hrs. The reaction mixture is cooled to room temperature. Sodium hydrogen carbonate is added into the reaction mass. The reaction mass is stirred at room temperature for about 5 hrs. The solid barium carbonate is filtered. 25 kg L-aspartic acid is added into the reaction mass and the mixture is stirred at room temperature for about 5 hrs. pH of the resulting mass should be 5.0-6.5. The mass is spray dried to get white solid L-ornithine L-aspartate with higher yield.
Note: The solid waste, barium carbonate is recycled to barium hydroxide octahydrate for reusing further in the process
TOXICITY PROFILE
S.N. Type of Toxicity Details of Toxicity Presence in present invention
1 Acute and Chronic Toxicity L-ornithine is generally well-tolerated, with no significant acute or chronic toxicity reported at therapeutic doses.
L-aspartic acid is a non-essential amino acid involved in various metabolic pathways. It is generally considered safe, with no significant acute or chronic toxicity reported at normal dietary levels NA
2 Carcinogenicity No carcinogenic effects have been associated with L-ornithine.
No carcinogenic effects have been associated with L-aspartic acid.
Direct long-term studies specifically evaluating the carcinogenic potential of LOLA are limited. However, several factors suggest a low likelihood of carcinogenicity. NA
3 Genotoxicity No mutagenic effects have been associated with L-ornithine. No mutagenic effects have been associated with L-aspartic acid.
Direct studies on the genotoxicity of LOLA are limited. However, research on its individual components provides insight. This suggests a low likelihood of genotoxicity for LOLA. NA
4 Neurotoxicity Current clinical evidence does not indicate that LOLA possesses neurotoxic properties. On the contrary, LOLA has demonstrated neuroprotective effects in patients with HE. NA
Table 2: Toxicity profile of LOLA
The present manufacturing process of L-ornithine L-aspartate has Chloride (NMT 0.03%), Ammonium (NMT 0.02%) and sulphate (NMT 0.02%) contents in all the batches observed below detection label which show no toxicity in the present invention.
IMPURITY PROFILE:
Related Impurity profile:
According to the procedure and key starting material, five related substances in L-Ornithine L-aspartate are possible which are tabulated below (Table-3):

Table-3 (List of related impurities)
Sl. No. Impurity Origin of impurity Fate of the impurity
1. Unreacted L-arginine
KSM ND by HPLC and 1H-NMR
2. Unreacted L-aspartic acid
KSM ND by HPLC and 1H-NMR.
3. D-Aspartic acid
KSM ND in the starting material (L-Aspartic acid)by HPLC and also in 1H-NMR.
4. β-Alanine
KSM ND in the starting material (L-Aspartic acid) by HPLC.
5. Putrescine
KSM ND in the KSM and LOLA by HPLC and in 1H-NMR.
Since our L-Aspartic acid (KSM), L-Arginine (KSM) and L-ornithine L-aspartic acid are free from the above related impurities as supported by the following HPLC graphs (Fig. 3, 4 and 5), we can conclude that, the related impurities are controlled in the quality of KSM
Fig. 3: HPLC Graph of L-arginine

Fig. 4: HPLC Graph of L-Aspartic acid

Fig. 5: HPLC Graph of L-Ornithine L-Aspartate (LOLA)
The above HPLC graphs of L-arginine, L-Aspartic acid and L-Ornithine L-aspartate confirms the absence of any related impurities.
Nitrosamine Impurity (In Line With FDA):
The term nitrosamine describes a class of compounds having the chemical structure of a nitroso group bonded to an amine (R1 N(-R2 )-N=O), as shown in Fig.6. The compounds can form by a nitro sating reaction between amines (secondary, tertiary, or quaternary amines) and nitrous acid (nitrite salts under acidic conditions).
Fig.6 Representative Reaction to Form Nitrosamines:
FDA 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) (Fig. 7). 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 are not used, hence we declare that, our APIs are free from any nitrosamine impurities.
Chemical Structures of Potential Small-Molecule Nitrosamine Impurities in APIsand Drug Productsexplained in figure 7 below-

Fig 7: List of Nitrosamine Impurities
Table 4: Risk Assessment (In line with FDA guideline):
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
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 solvent 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
The above review (Table 4) is expected to provide us high level of confidence for the absence of Nitrosamine impurities in our L-ornithine l-aspartate product.
For Example, If we consider traces of nitrosamine impurity is formed due to environmental contamination it undergoes decomposition under acid catalyzed reaction condition of Ca(II); (Ref:J. Org. Chem.,1979, 44, 784-786) in the following mechanistic pathway (Fig. 8). The general mechanism is proposed by the inventors.

Fig. 8: Proposed Mechanism of decomposition of nitrosamine impurity
From the above mechanism and reaction scheme, we can establish that, there is no nitrosamine in our L-Ornithine L-Aspartate.
The present invention used only water as solvent in entire process of preparation of L-Ornithine L-Aspartate and not used any organic solvent so the final product is free from organic volatile impurities.
PHYSICOCHEMICAL CHARACTERIZATION
Physical Properties (Typical values):
Description A white odorless crystalline Powder
LOD (105⁰C for 4 hrs.) Not more than 7.0%w/w
pH (2%w/v in aq. Soln.) 5.0-6.5
Assay (By HPLC) 98.0-101.0% w/w
Transmittance at 430nm of 2.5%w/v solution in water Solution should be clear and colorless and ≥98.0%
Table 5: Physical properties of LOLA batch
ROBUSTNESS OF PROCESS
The WBCIL manufacturing process of L-ornithine L-aspartate is controlled by optimization of the different reaction parameters. To check the robustness of the manufacturing process, the process is repeated by the scale up from 20 g to 100g in the laboratory. All the analytical results are found consistent. Chloride (NMT 0.03%), Ammonium (NMT 0.02%) and sulphate (NMT 0.02%) contents in all the batches are observed below detection label. Some major analytical data (Assay, pH, LOD and Transmittance) of six different batches are presented as graphical presentation to explain the robustness of the manufacturing process in below Table 6-
Experiment No. 1 2 3 4 5 6
Assay (98.0-101.0%w/w) 99.63 98.34 101 99.51 100.6 100.86
pH (5.0-6.5) 6.2 6 6.5 6.2 5.7 5.9
LOD NMT 7.0% w/w 6.01 2.05 4.32 2.27 3.60 6.50
Transmittance at 430 nm (Should clear ≥98.0%) 98.5 99.2 98.8 98.7 99.3 99.5
Table 6: Assay, pH, LOD and Transmittances of six batches
As per the above analytical data, we can conclude that, the batches are compiled as per the desired specifications. So, we can say the manufacturing process is robust and easily scalable.
Repeated analytical tests demonstrated consistent assay (98-101%), optimal pH (5.0-6.5), low LOD (<7%), and high transmittance (>98%) across batches
Purity and identification of L-Ornithine L-Aspartate
Infrared Absorption (IR):
The major characteristic peaks of L-ornithine L-aspartate are identified by IR are presented below:

Figure 9: Infrared Absorption (IR) of LOLA
Based on the above IR spectrum of L-Ornithine L-aspartate (LOLA),the following characteristics key peaks are detected, along with their likely functional group assignments are tabulated in Table-7:
Table 7: Wave number and Assignment
Wave number (cm-1) Assignment Description
3012 N–H stretch (amine) Asymmetric stretching of primary amine (Orn)
2926, 2850 (broad) O–H / N–H stretch Hydrogen bonded OH or NH₂ (overlapping)
1588–1558 COO⁻ asymmetric stretch Carboxylate (from aspartate & ornithine)
1426 COO⁻ symmetric stretch Carboxylate salt structure
1385, 1310 C–N stretch / CH bending Amine group or CH₂ wagging
1260–1030 C–O, C–N, N–H bending Multiple bands—amine + carboxylate region
849.8, 820.6 N–H wag or CO bending Possibly δ(NH₂) or COO⁻ deformation
677–591 COO⁻ or skeletal bending Fingerprint of COO⁻ and amino acid backbone
509–463 Ring or skeletal vibrations Less diagnostic, but confirms structure
This spectrum is consistent with LOLA, where both L-ornithine and L-aspartate exist in zwitterionic salt form. The presence of multiple amine and carboxylate functionalities is clearly reflected in the spectrum.
1H-NMR spectra of L-Ornithine L-aspartate:
The structure of L-Ornithine L-aspartate (LOLA) was confirmed by 1H-NMR which is presented below:


Figure 10: H-NMR of LOLA
Mass Spectra of L-Ornithine L-aspartate:
Based on its molecular formula [C₅H₁₂N₂O₂], the calculated mass of L-ornithine is 132.12. In the HRMS spectrum (ESI, negative mode), an m/z value of 132.05 corresponds to the L-ornithine free base. Similarly, for L-ornithine L-aspartate (LOLA), with a molecular formula of [C₉H₁₉N₃O₆], the calculated mass is 265.26. The observed m/z value of 287.10 in the negative ESI mode likely results from the formation of a sodium adduct followed by the loss of a proton, [M + Na - H] ⁻. These HRMS data confirm the formation of L-ornithine-L-aspartate.
Figure 11: HRMS of LOLA
THERMAL ANALYSIS
DSC data of L-Ornithine L-aspartate:
The DSC (Differential Scanning Calorimetry) data in the graph represents the thermal behavior of L-Ornithine L-Aspartate as the temperature is increased.

Figure 12: DSC of LOLA
Analysis of DSC graphs:
First Endothermic Event (~130–133°C):
Interpretation:
Represent loss of hydration water. This is a physical change, not associated with decomposition.
Second Endothermic Event (~211–233°C):
Interpretation:
Likely the melting point or thermal degradation point. Correlates well with the TGA decomposition end (~210°C). Indicates melting of LOLA salt.

TGA (Thermogravimetric analysis) of L-Ornithine L-aspartate (LOLA):
TGA thermograms of L-Ornithine L-aspartate shows the following characteristics natures:

Figure 13: TGA of LOLA
Analysis of TGA Graph:
Stability:
LOLA shows excellent thermal stability up to ~185°C, with no observable degradation or volatilization.

Major degradation:
The sharp weight loss (48.54%) beginning at 187.3°C corresponds to the breakdown of the zwitterionic salt structure (L-ornithine + L-aspartate).
Residual Mass (~51%):
Remaining mass likely corresponds to non-volatile inorganic residues or carbonaceous char from organic components.
IR, 1H-NMR, Mass spectra, DSC, TGA clearly characterize the purity and structure
THERMAL ANALYSIS:
• DSC confirms hydration loss at ~130°C and decomposition at ~211-233°C.
• TGA indicates stability until ~185°C, with major degradation at ~187°C.
• Thermal Stability: DSC and TGA analyses confirm stable thermal behavior, with hydration loss at ~130°C, and decomposition initiating around ~187°C, indicating high stability and robustness of the product.

, C , Claims:I/We claim

1. An one-step in-situ process of preparation of L-Ornithine L-Aspartate (LOLA) comprising of:
a) adding of barium hydroxide octahydrate and L-arginine in water in molar ratio of 0.3 to 6.0;
b) stirring the reaction mixture at maximum 80 0C for maximum 20 hrs for complete dissolution;
c) cooling the reaction mixture after step (b) at below 30 0C;
d) adding sodium bicarbonate for formation of barium carbonate and L-ornithine free base and stirring at below 30 0C for maximum 10 hrs;
e) filtering and removing barium carbonate;
f) adding L-aspartic acid in mole ratio 3:3 with respect to Argnine and stirring at below 30 0C for maximum 10 hrs;
g) drying the final product to get the desired non-hygroscopic, industrially scalable and stable L-Ornithine L-Aspartate (LOLA) with higher yield through spray drier.
2. The process claimed in claim 1 wherein the barium hydroxide octahydrate added in water maximum 1:20 in step (a).
3. The process claimed in claim 1 wherein the sodium bicarbonate added in step (d) in molar ratio of 1.5:1 with respect to barium hydroxide octahydrate.
4. The process claimed in claim1 wherein step (a) to step (d) of claim 1 involves cleavage of the guanidino side chain of L-arginine resulting formation of L-ornithine free base.
5. The process claimed in claim 1 wherein the by product barium carbonate produced in step (e) of claim 1 got recycled to barium hydroxide and reused in the process of claim 1 which show the zero by product or waste of claim 1.
6. The process claimed in claim 1 wherein the process is greener process and followed the principle of green chemistry and energy consumption is less because of temperature range less than 80 0C and other remaining process at below 30 0C which is room temperature.
7. The process claimed in claim 1 wherein the final product and the process is free from nitrosamine impurity and organic volatile impurities.
8. The process claimed in claim 1 wherein the final product and the process is free from toxic elements like lead, cadmium, arsenic, ammonium, sulphate and chloride.
9. The process claimed in claim 1 wherein the final product and the process is free from related impurities and non-hygroscopic.
10. The process claimed in claim 1 is robust wherein analytical test across multiple batches of final product, maintaining consistent assay (98.0%-101.0% w/w), pH (5.0-6.5), LOD (<7%), and high transmittance (≥98.0%).
11. The process claimed in claim 1 is cost effective, industrially scalable process to obtain the stable and higher yield of L-Ornithine L-Aspartate (LOLA).