Claims:1) A process for preparing homogeneous blends of lipidated glycines (Formula-I) in flake form

Formula-I
wherein R = C7 alkyl and C10 alkenyl group with terminal double bond
comprising the steps of
I) Reacting alkanoyl chlorides with glycine in the presence of inorganic base to obtain alkali metal salt of lipidated glycine;
II) Acidifying the reaction mass of step I with sulphuric acid and subsequent phase separation at 60 °C - 65 °C to remove aqueous layer;
III) Washing the organic layer of step II at 60 °C – 65 °C with water;
IV) Removal of trapped water from the organic layer of lipidated glycines of step III) by using wiped film evaporator;
V) Flaking the molten lipidated glycines of step IV;
wherein the lipidated glycines (Formula-I) content is not less than 96% by weight and free fatty acid content is not more than 3% by weight;
and the water used in step (III) is not more than 0.25 Kg/Kg of the lipidated glycines of Formula-I.
2) The process as claimed in Claim 1, wherein ratio of N-capryloyl glycine to N-undecylenoyl glycine is 1.0 : 3.0 to 3.0 : 1.0.

3) The process as claimed in Claim 1, wherein the free glycine in lipidated glycines (Formula-I) is not more than 0.3% w/w.
, Description:FIELD OF THE INVENTION

The present invention relates to a process of manufacturing homogeneous blend of lipidated glycines, namely, N-undecylenoyl glycine and N-capryloyl glycine for preservation of personal care formulations. It further relates to an efficient process for preparing homogeneous blend of lipidated glycines in flake form, to avoid dusting.

BACKGROUND AND PRIOR ART OF THE INVENTION

Both N-capryloyl glycine and N-undecylenoyl glycine are well-known antimicrobials. The possibility of employing N-capryloyl glycines as an anti-microbial preservative for personal care products was reported in 1996 (Cosmetics & Toiletries, 17(3), 11-13, 16-19, (1996)). Similarly, N-undecylenoyl glycine was reported almost five decades ago for treating skin disorders by the Japanese scientists (JP 49093521 (1974)). WO 19927902 (1992) teaches useful compositions comprising both N-capryloyl glycine and N-undecylenoyl glycine exploiting their unique properties for personal care application. US20040096526 reveals use of both lipidated glycines along with some plant extracts for preservation of personal care products. Luigi Rigano predicted (Cosmetics & Toiletries, 128, 458-461(2013)) increasing use of these two glycines for preservation of baby care products. Recently, Koshti et al. reported synergistic composition of these two lipidated glycines in water and phenoxy ethanol in the form of a microemulsion for preservation of personal care products (PCT/IN2014/000394). Commercially, both lipidated glycines, N-capryloyl glycine and N-undecylenoyl glycine, are available individually from Seppic, France (Lipacide C8 and Lipacide UG respectively) in the form of fine powder. Similarly, a blend of these two lipidated glycines in fine powder form is available from AE Chemie Inc, USA, under the trade name of AE PureProTek as a preservative for personal care formulations. Thus, the utility of the lipidated glycines is well established and currently they are offered as individual separate entities as well as blend of the two in the form of fine powder.

Almost all effective, work-horse antimicrobial preservatives such as formaldehyde, DMDM hydantoin, imidazolidinyl urea and other formaldehyde releasers, parabens, triclosan, methyl isothiazolinone (MIT), chloromethyl isothiazolinone (CIT), iodopropynyl butyl carbamate (IPBC), bromo-nitro propandiol (Bronopol) have been mired into controversies arising due to serious toxicity issues to human and in some cases environment (PCT/IN2014/000394). Hence, personal care industry is looking for an alternative that would be cost effective and safe to human and environment. The lipoglycines, N-capryloyl glycine and N-undecylenoyl glycine, meet these expectations by being effective antimicrobials, safe and biodegradable preservatives. However, these lipoglycines are effective against bacteria and fungi at a concentration level of 0.5% to 1.0% based on their minimum inhibitory concentration (MIC) data. Effective usage level for preservation of bulk products like shampoo or body wash is at 0.75% to 1.5% when used alone for the preservation purpose. The current market prices in the range of 35 USD/Kg to 40 USD/Kg for these lipoglycines coupled with high effective dosage level make them somewhat unattractive for application of preservation in bulk consumer products like shampoos and body-washes.

In addition to the prohibitive cost for the intended bulk usage as preservative, the biggest concern with powder form of N-capryloyl glycine and N-undecylenoyl glycine is the hazard of the dust explosion (Storage and Handling sections of material safety data sheets of Lipacide C8G and Lipacide UG). Dusting of powders is always a concern and special protective equipment are required to prevent the adverse impact on human work force as well as on the environment. The lipidated glycines are classified as hazardous substances and reported to be toxic to aquatic life with a long term effect. Thus, release of the said lipoglycines to the environment and exposure to humans must be prevented at any cost. In this respect, dusting property associated with the powder form is the most difficult to deal with, particularly on a multi-tonne scale of manufacture. During manufacture and subsequent use of fine powder of lipoglycines, special precautions must be taken against static discharges leading to dust explosions. The powder form of N-capryloyl glycine and N-undecylenoyl glycines is violently explosive (Dust explosion test done by Hartmann apparatus). The minimum ignition energy for lipoglycines in powder form is ~55 mJ, which clearly indicates that both the lipidated glycines possess dust explosion property and extreme precautions against static ignition is a must while handling the powder form of lipidated glycines. Any facility engaged in manufacture of combustible powder needs an elaborate set up with a) dust control measures, b) ignition and static discharge control measures and c) other general protection measures in place.

In view of the large potential for the lipoglycines as ‘biodegradable and safe antimicrobial preservatives’ for personal care formulations, it is essential that process of manufacture is cost-effective without compromising on the quality.

Thus, in view of huge potential to be anti-microbial preservative for personal care products, there is a need for an efficient and cost effective manufacturing process that would avoid the potential danger of dust explosion due to static discharges.

The present invention relates to the manufacture of the homogeneous mixtures of antimicrobial lipidated glycines by a cost-effective process that delivers the product in non-explosive solid form of ‘flake’.

OBJECTS OF THE INVENTION

i. It is an object of the present invention to provide a non-dusting solid form of blend of lipidated glycines, namely, N-capryloyl glycine and N-undecylenoyl glycine to avoid the dust-explosion hazard and also to avoid toxic effect on human and eco-system due to the exposure to the dust.

ii. Another object of the present invention is to provide a cost-effective manufacturing process that would be sustainable. The developed sustainable process covers high yield with lesser unit operations and less effluent generation.

The inventors of the present patent application have developed a process that meets the above mentioned objectives.

SUMMARY OF INVENTION

A process for preparing homogeneous blends of lipidated glycines (Formula I) in flake form

Formula-I
wherein R = C7 alkyl and C10 alkenyl group with terminal double bond
comprising the steps of
I) Reacting alkanoyl chlorides with glycine in the presence of inorganic base to obtain alkali metal salt of lipidated glycine;
II) Acidifying the reaction mass of step I with sulphuric acid and subsequent phase separation at 60 °C - 65 °C to remove aqueous layer;
III) Washing the organic layer of step II) at 60 °C – 65 °C with water;
IV) Removal of trapped water from the organic layer of lipidated glycines of step III) by using wiped film evaporator;
V) Flaking the molten lipidated glycines of step IV);

Wherein the lipidated glycines (Formula I) content is not less than 96% by weight and free fatty acid content is not more than 3% by weight;
and the water used in step (III) is not more than 0.25 Kg / Kg of the lipidated glycines of Formula (I).

In an another aspect, the present invention is directed to personal care compositions such as shampoo, hand wash, body wash, face wash, hair conditioner, creams and lotions that are preserved using flake form of the lipidated glycines of the present invention.

The above described features, benefits and advantages of the present disclosures will be appreciated and understood by those skilled in the art from the following detailed description and the claims.

DETAILED DESCRIPTION OF INVENTION

The manufacturing processes described in literature and prior art for solid N-acyl amino acids have been designed for powder form. For example, WO2009118493 reports continuous aqueous phase synthesis of N-acylated amino acids by continuously feeding the alkali metal salt of amino acid and acid chloride into a reactor at alkaline pH, followed by precipitation with strong acid, filtration and drying to yield the N-acyl glycines as fine powder.
As mentioned in the background section, the commercially available N-capryloyl glycine and N-undecylenoyl glycine are fine powders and the blend of these two N-acyl glycines that is commercially available is also in the fine powder form. The powder form of N-acyl glycines of Formula-I, is associated with serious issues concerning both human and environment exposure to fine dust and dust explosion due to static discharge. To take care of both the aspects one has to invest in specific equipment to handle and eliminate dust collection.

For controlling dust explosion hazard, significant precautionary steps need to be taken. In addition, collecting precipitated N-acyl glycines and drying the wet cake adds on to the number of steps and unit operations like agitated vacuum filtration and fluidized bed drying and bagging of fine powder. Typical process of acidifying the product of Schotten-Baumann chemistry, between alkanoyl chloride and glycine in the presence of an inorganic base, result in white precipitate of N-acyl glycines (J. Am. Chem. Soc., 1956, 78 (1), 172–174). The acidification of reaction mass (pH 2.0) and subsequent washing of the precipitated acyl glycines with water (to make acyl glycine free from mineral acidity and salts) and filtration are done at ambient temperature. The wet mass is filtered with agitated Nutsche type of filters to remove the trapped water and subsequently the moist powder is dried using fluidized bed dryer by gradually raising the temperature of hot air. This multistep operation needs to be done carefully to avoid the acidic hydrolysis of amide linkage while removing trapped water and the final drying of fine powder of lipidated glycines. This results in N-acyl glycines without causing any damage to the peptide linkage due to acidity.

The inventors of the present patent application have surprisingly discovered the processing conditions of acidification and subsequent washing N-acyl glycines in molten form that does not cleave the peptide bond and it is possible to convert the molten N-acyl glycines into flake form without generating any unwanted impurity.

The process for preparing homogeneous blends of lipidated glycines (Formula-I, RCO is capryloyl and undecylenoyl group) in flake form is depicted in flow diagram (Figure I).

Formula-I

The manufacturing process involves following five steps:
I) Reaction of alkanoyl chlorides with glycine in the presence of a base;
II) Acidifying the reaction mass of step I with sulphuric acid and subsequent phase separation at 60 °C - 65 °C to remove aqueous layer;
III) Washing the organic layer of step II) at 60 °C – 65 °C with water;
IV) Removal of trapped water from the organic layer of lipidated glycines of step III) by using wiped film evaporator;
V) Flaking of the molten mass of lipidated glycines.

Figure I
I) Reaction of alkanoyl chlorides with glycine in the presence of a base
Alkanoyl chlorides used in the present patent application are mixture of capryloyl chloride and undecylenoyl chloride. Alkanoyl chlorides were prepared as per the procedure reported in the Patent Application (WO/2014/030038) by Koshti et al.

Mixture of fatty acid chlorides are reacted with glycine in aqueous medium in the presence of an inorganic base at 20 °C to 30 °C to afford 50% aqueous solution (50% concentration) of alkali metal salt of acyl glycines. The inorganic base is selected from hydroxides or carbonates of potassium and sodium or ammonium hydroxide.

II) Acidifying the reaction mass of step I with sulphuric acid and subsequent phase separation at 60 °C - 65 °C to remove aqueous layer
The acidification of the stirred aqueous solution of alkali metal salts of N-acyl glycines is done with concentrated sulphuric acid till pH of 2.0 is attained. Temperature of the reaction mass is then raised between 60 °C to 65 °C. Cessation of stirring results in clean separation of two phases. The bottom aqueous layer is removed, cooled and filtered to recover acyl glycines (0.7% of the final product (Formula-I)). The bottom aqueous layer has the composition as shown in Table–I. The effluent generated is 1.96 Kg/ Kg of the final product (Formula-I). The effluent has very low load of organic matter i.e., acyl glycine 0.01% and free glycine 0.3%. The effluent has Chemical Oxygen Demand (COD) of 8000 ppm.

It is observed that under acidic conditions, separation of aqueous and organic phase does not take place when the temperature of the acidified mass is 55 °C or below (Example 5) whereas phase separation at temperature of 95 °C or above leads to significant hydrolysis of the peptide bond which results in generation of fatty acid (Example 4).

III) Washing the organic layer of step II) at 60 °C - 65 °C with water
The organic layer is washed with water and again phase separation is effected at 60 °C to 65 °C. The amount of water used for washing is limited to less than 0.25 Kg/Kg of the final product (Formula-I). The minimum water quantity is used to keep the effluent generated at minimum. The separated aqueous layer containing acyl glycine (0.09%) is reused in the next batch. Composition of aqueous layer is as shown in Table-I.
The total water consumption for the entire process is 1.63 Kg/Kg of the final product and the total effluent generated is 1.96 Kg/Kg of the final product, as evident in Example 1 of experimental section.

Parameters Aqueous layer after phase separation (Step-II) Aqueous layer after washing of organic layer (Step-III)
Quantity (Kg) 92 6.1
Solids (%) 30.98 13.64
NaCl Content (%) 13.2 6.95
Na2SO4 Content (%) 17.6 6.3
Free Glycine (%) 0.3 0.1
Capryloyl Glycine (%) 0.01 0.09
Water (%) 69.02 86.36

Table-I

IV) Removal of trapped water from the organic layer of lipidated glycines of step III) by using wiped film evaporator

Trapped water in the molten mass of N-acyl glycines is removed by wiped film evaporator under reduced pressure.

Even though most of mineral acidity is washed, there is still some amount of trapped water (25%) and the N-acyl glycines are sufficiently acidic to catalyze the hydrolysis of amide linkage in the presence of trapped water at elevated temperature. This results in acidic hydrolysis of N-acyl glycine generating impurities of glycine and fatty acids in the product. Hence the water removal before flaking needs to be done within shortest time period in an efficient manner.

The conventional way of removing trapped water is by evaporating water at 80 °C -95 °C under vacuum. This accelerates the hydrolysis process as the residence time of product with water is higher under hydrolysis environment i.e. presence of water and temperature. The product obtained after removal of trapped water by conventional method (Example 3) contains higher free fatty acid (FFA), affecting quality of product and lowering the yield. Glycine generated due to hydrolysis during trapped water removal stage (Step IV) remains in the product as an impurity. Also higher batch size shall lead to more exposure time to hydrolysis conditions resulting in higher FFA. Therefore, it is necessary to remove water in continuous mode to reduce time of exposure to hydrolysis conditions. In the present invention, the trapped water in Step (IV) is removed using techniques which involve less residence time such as Wiped Film Evaporation. As compared to conventional method of water removal, the method disclosed in the present invention ensures less time of exposure of lipidated glycines to hydrolysis conditions, irrespective of the batch size and hence results in significantly lower levels of free fatty acids and glycine. The free glycine content in the lipidated glycines is less than 0.2% and the moisture content is less than 1%.
Following is the analysis of the reaction mass of Step IV of Example 1 and 3 before the trapped water removal:

Water content (%) 25
Free Fatty acid (%) on dry basis 2
Free glycine (%) on dry basis 0.01

Following is the comparative data (Table II) for trapped water removal by wiped film evaporator (Example-1) and conventional process (Example-3)

Parameters Removal of water using wiped film evaporator (Example 1) Removal of water by conventional technique (Example 3)
Free Fatty acid (%) 2.52 3.9
Free glycine (%) 0.01 0.3
Lipidated glycines content (%) 96.35 94.85
Moisture 0.51 0.6
Table-II
As is evident from Table-II, there is a significant increase in the free fatty acid content when trapped water is removed by conventional process as compared to that in case of wiped film evaporator.

V) Flaking of the molten mass of lipidated glycines
The molten acyl glycines (at 95 °C) from the wiped film evaporator are drum flaked to yield irregular flakes with varying thickness. The molten mixture of N-acyl glycines from wiped film evaporator can be converted into pellets or prills by spray chilling. The flake can be easily extruded to create the needle or noodle form of varying diameter and length.

The acyl glycine flakes of the present patent application have N-capryloyl glycine to N-undecylenoyl glycine in the ratio of 1: 3 to 3:1 w/w. In Example 1 the ratio of two glycines is 1:1 whereas in Example 2, N-capryloyl glycine to N-undecylenoyl glycine is 1: 3.

Antimicrobial efficacy of acyl glycines of the present invention (Formula-I) is tested on both leave-on products as well as rinse-off formulations. Acyl glycines of Example 1 have been used as preservative at 0.8% to 1% level in shampoo, face wash and a cream formulation (Example 6, 7 and 8) and the formulations have been challenge tested as per the CTFA guidelines. According to the CTFA guidelines, there should be =3 log reduction in bacteria and =1 log reduction in case of yeast and mould within 7 days, with no increase in their growth after 7 days. All the 3 formulations passed the CTFA criteria.

Advantages of the invention

1) The present invention provides the homogeneous blend of N-capryloyl glycine and N-undecylenoyl glycine in the flake form. In contrast to explosive nature of fine dust arising from the powder form, the flakes or the pellets are completely free from fine dust and flakes are not susceptible to ignition by static discharges.
2) As against the existing powder form of lipidated glycines, the manufacture of flake form of homogeneous blend of the two lipoglycines employs significantly less number of unit operations like filtration of powder (5 to 15 micron of particle size, agitated Nutsche filter) and fluidized bed drying. Less number of unit operations lowers the batch cycle time as well as energy requirement and make the process cost-efficient.
3) Process of the present invention generates very little effluent and hence it is quite sustainable.
4) The present invention provides the lipidated glycines in the solid form which overcomes health and environmental hazards due to exposure to the dust, of powder form of product that is currently available.

EXAMPLES

The present invention is now described by way of working on non-limiting illustrative examples. The details of the invention provided in the following examples are given by the way of illustration only and should not be construed to limit the scope of the present invention.
Sodium laureth sulphate (Galaxy LES) and cocomonoethanol amide (Galaxy 100) were obtained from Galaxy Surfactants Ltd. Caprylic and undecylenic acids have been procured from Vegetable Vitamin Foods Company (VVF India Ltd).

Example 1: Preparation of blend of N-capryloyl glycine and N-undecylenoyl glycine (mole ratio, 1:1) in flake form
Step 1: To a stirred mixture of glycine (83 Kg, 1.11 Kgmol) in water (234 Kg) at 25 °C is added mixture of capryloyl chloride (100 Kg, 0.6 Kgmol) and undecylenoyl chloride (100 Kg, 0.5 Kgmol) and sodium hydroxide solution (87 Kg of 48% aqueous solution, 2.16 Kgmol) simultaneously while maintaining temperature between 20 °C to 25 °C and pH between 10.0 to 11.0. The addition takes 4 to 5 hours depending on the efficiency of temperature control. The reaction mass is stirred for additional two hours.
Step 2: The reaction mass of step 1 (130 Kg) is acidified by adding sulfuric acid (11.0 Kg, 0.11 Kgmol). It is heated to 65 °C and the aqueous layer is separated. The aqueous layer at room temperature is filtered to recover the lipidated glycines in powder form (0.7% of the final product, i.e. 0.3 Kg). To the organic mass is added 11 Kg water (to remove remaining salts and mineral acidity) and the temperature is raised to 65 °C. The mass is allowed to separate into two phases while maintaining the temperature. The 6.1 Kg lower aqueous layer (containing 13% salts and 0.09% capryloyl glycine as shown in Table-I) is removed. The 59.9 Kg top organic layer containing 24% water is continuously fed to wiped film evaporator for the removal of trapped water (0.3 Kg/ Kg of the final product). The molten mass (46 Kg) is drum flaked.
The HPLC analysis (reversed phase chromatography, C18 bonded column, mobile phase: acetonitrile-water, flow rate of 1 ml/min, UV detection at 246 nm) of flakes indicated it to be in 1: 1 ratio of N-undecylenoyl glycine and N-capryloyl glycine and total free fatty acids comprising caprylic acid and undecylenic acid is 2.52% w/w.

The HPLC chromatogram is as follows (Figure II):

Figure II: HPLC chromatogram of flakes

Analysis:
Parameters Analysis
Nature / Appearance Off-white flakes
Acid Value, mg KOH/g 248.65
Active Content (%) 96.35
a. Capryloyl glycine (%) 48.03
b. Undecylenoyl glycine (%) 48.32
Fatty Acid Content (%) 2.52
NaCl Content (%) 0.2
Na2SO4Content (%) 0.3
Glycine Content (%) 0.01
Moisture Content (%) 0.51
Melting Point, °C 88

Example 2: Preparation of blend of N-capryloyl glycine and N-undecylenoyl glycine (mole ratio, 1:3) in flake form
Step 1: To a stirred mixture of glycine (78.63 Kg, 1.048 Kgmol) in water (271.64 Kg) at 25 °C is added mixture of capryloyl chloride (50 Kg, 0.307, Kgmol) and undecylenoyl chloride (150 Kg, 0.740 Kgmol) and sodium hydroxide solution (175 Kg of 48% aqueous solution, 2.09 Kgmol) simultaneously while maintaining temperature between 20 °C to 25 °C and pH between 10.0 to 11.0. The addition takes 4 to 5 hours depending on the efficiency of temperature control. The reaction mass is stirred for additional two hours.
Step 2: The reaction mass of step 1 (130 Kg) is acidified with sulphuric acid (12 Kg, 0.12 Kgmol) and is heated to 65 °C under stirring. On standing, separated aqueous layer is removed. The aqueous layer is filtered at room temperature to recover the lipidated glycines in powder form (0.7% of the final product; i.e. 0.3 Kg). The organic layer is washed with additional water (11 Kg) to remove remaining sodium sulphate and sodium chloride and the traces of mineral acidity. The temperature of the mass is raised to 65 °C while being stirred and then is allowed to separate into two phases while maintaining the temperature. The lower aqueous layer (containing 13% salt and 0.09% capryloyl glycine) is removed. The top organic layer is continuously fed to wiped film evaporator for the removal of water (0.3 Kg/ Kg of the final product). The molten mass (47 Kg) is drum flaked to obtain flakes.
Analysis:
Parameters Analysis
Nature / Appearance Off-white flakes
Acid Value, mg KOH/g 245
Active Content (%) 96.64
a. Capryloyl glycine (%) 24.21
b. Undecylenoyl glycine (%) 72.43
Fatty Acid Content (%) 2.4
NaCl Content (%) 0.25
Na2SO4Content (%) 0.3
Glycine Content (%) 0.02
Moisture Content (%) 0.4
Melting Point, °C 89

Example 3:

Comparative Example

Preparation of blend of N-capryloyl glycine and N-undecylenoyl glycine (mole ratio, 1:1) in flake form with phase separation at 65 °C and trapped water removal by conventional method
Step 1: To a stirred mixture of glycine (83 Kg, 1.11 Kgmol) in water (234 Kg) at 25 °C is added mixture of capryloyl chloride (100 Kg, 0.6 Kgmol) and undecylenoyl chloride (100 Kg, 0.5 Kgmol) and sodium hydroxide solution (87 Kg of 48% aqueous solution, 2.16 Kgmol) simultaneously while maintaining temperature between 20 °C to 25 °C and pH between 10.0 to 11.0. The addition takes 4 to 5 hours depending on the efficiency of temperature control. The reaction mass is stirred for additional two hours.
Step 2: The reaction mass of step 1 (130 Kg) is acidified by adding sulfuric acid (11.2 Kg, 0.11 Kgmol). It is heated to 65 °C and the aqueous layer is separated. The aqueous layer at room temperature is filtered to recover the lipidated glycines in powder form (0.7% of the final product, i.e. 0.29 kg). To the organic mass is added 11 Kg water (to remove remaining salt and mineral acidity) and the temperature is raised to 65 °C. The mass is allowed to separate into two phases while maintaining the temperature. The lower aqueous layer (containing 13.3% salts and 0.09% capryloyl glycine) is removed. The water from top layer (0.3 Kg/Kg of final product) is removed by increasing the temp to 80 °C – 95 °C under reduced pressure of 600 mm Hg. Traces of water are removed by applying high vacuum of < 10 mm Hg for 10 minutes. The molten mass (45.6 Kg) is drum flaked to obtain flakes.
The HPLC analysis shows lipidated glycines content to be 94.85% and free fatty acid content is 3.9% w/w.

Analysis:
Parameters Analysis
Nature / Appearance Off-white flakes
Acid Value, mg KOH/g 250
Active Content (%) 94.85
a. Capryloyl glycine (%) 47.1
b. Undecylenoyl glycine (%) 47.75
Fatty Acid Content (%) 3.9
NaCl Content (%) 0.3
Na2SO4Content (%) 0.25
Glycine Content (%) 0.3
Moisture Content (%) 0.6
Melting Point, °C 87

Example 4:

Comparative Example

Preparation of blend of N-capryloyl glycine and N-undecylenoyl glycine (mole ratio, 1:1) in flake form with phase separation at 95 °C and trapped water removal by conventional method
Step 1: To a stirred mixture of glycine (83 Kg, 1.11 Kgmol) in water (234 Kg) at 25 °C is added mixture of capryloyl chloride (100 Kg, 0.6 Kgmol) and undecylenoyl chloride (100 Kg, 0.5 Kgmol) and sodium hydroxide solution (87 Kg of 48% aqueous solution, 2.16 Kgmol) simultaneously while maintaining temperature between 20 °C to 25 °C and pH between 10.0 to 11.0. The addition takes 4 to 5 hours depending on the efficiency of temperature control. The reaction mass is stirred for additional two hours.
Step 2: The reaction mass of step 1 (130 Kg) is acidified by adding sulfuric acid (11 Kg, 0.11 Kgmol). It is heated to 95 °C and the aqueous layer is separated. The aqueous layer at room temperature is filtered to recover the lipidated glycines in powder form (0.9% of the final product, i.e. 0.4 Kg). To the organic mass is added 11 Kg water (to remove remaining salt and mineral acidity) and the temperature is raised to 95 °C. The mass is allowed to separate into two phases while maintaining the temperature. The lower aqueous layer (containing 12.5% Salts and 0.09% Capryloyl glycine) is removed. The trapped water (0.3 Kg/Kg of final product) from organic layer is removed by increasing the temperature between 80 °C – 95 °C under reduced pressure of 600 mm Hg. Traces of water are removed by applying high vacuum of < 10 mm Hg for 10 min. The molten mass (46 Kg) is drum flaked to obtain flakes.
The HPLC analysis shows lipidated glycines content is 94.37% and total free fatty acid content of 4.6% w/w.

Analysis:
Parameters Analysis
Nature / Appearance Off-white flakes
Acid Value, mg KOH/g 252
Active Content (%) 94.37
a. Capryloyl glycine (%) 47.01
b. Undecylenoyl glycine (%) 47.36
Fatty Acid Content (%) 4.6
NaCl Content, (%) 0.3
Na2SO4Content, (%) 0.25
Glycine Content, (%) 0.4
Moisture Content, (%) 0.7
Melting Point, °C 87

Example 5:

Comparative Example

Preparation of blend of N-capryloyl glycine and N-undecylenoyl glycine (mole ratio, 1:1) in flake form with phase separation at 55 °C
Step 1: To a stirred mixture of glycine (83 Kg, 1.11 Kgmol) in water (234 Kg) at 25 °C is added mixture of capryloyl chloride (100 Kg, 0.6 Kgmol) and undecylenoyl chloride (100 Kg, 0.5 Kgmol) and sodium hydroxide solution (87 Kg of 48% aqueous solution, 2.16 Kgmol) simultaneously while maintaining temperature between 20 °C to 25 °C and pH between 10.0 to 11.0. The addition takes 4 to 5 hours depending on the efficiency of temperature control. The reaction mass is stirred for additional two hours.
Step 2: The reaction mass of step 1 (130 Kg) is acidified by adding sulfuric acid (11 Kg, 0.11 Kgmol). It is heated to 55 °C. Separation of two layers is not observed.
It is observed that temperature needs to be increased to 60 °C for phase separation to be effected.

Example 6: Preparation of shampoo: preservation with flakes of Example 1

Components Trade Name (% W/W)
Phase A
Water (Aqua) D.M.Water 45.70
Sodium laureth sulphate (28%, 2 EO) Galaxy LES 43
Phase B
Cocomonoethanol amide Galaxy 100 2.00
Cocamidopropyl Betaine (30%) Galaxy CAPB 6.7
Phase C
Preservative Flakes of Example 1 1.00
Citric acid 50% q.s. to pH 6 to 6.5
Sodium Chloride 1.5
EDTA 0.1
Phase D
Fragrance, Color q.s

Procedure: All ingredients of phase A are heated to 75 °C with gentle agitation. To it phase B is added and the mixing is continued till the whole mass becomes homogeneous. It is then allowed to come to room temperature with gentle stirring and Phase C is added and stirring continued till uniform mass is obtained. The pH is adjusted to 6 to 6.5 with aqueous citric acid (50%). The color and fragrance (phase D) are blended with the mass with gentle stirring.

Example 7: Preparation of face wash: preservation with flakes of Example 1
Components Trade Name (% W/W)
Water (Aqua) D.M.Water 71.2
Potassium cocoyl glutamate and sodium cocoyl isethionate Galsoft GLI21 15
Cocomonoethanol amide Galaxy 100 2.00
Cocamidopropyl Betaine (30%) Galaxy CAPB 10
Polyethylene glycol 150 (PEG 150) 1
Preservative Flakes of Example 1 0.8

Procedure:

All the ingredients are heated to 75 °C under slow stirring and the mixing is continued till the whole mass becomes homogeneous. It is then allowed to come to room temperature with gentle stirring. The pH is adjusted to 6 to 6.5 with aqueous citric acid (50%).

Example 8: Preparation of O/W cream: preservation with flakes of Example 1
Components Trade Name (% W/W)
Phase A
Water (Aqua) D.M.Water 70.00
Glycerin Glycerin 2.00
Paraffinum Liquidum Mineral oil 15.00
Stearic Acid Stearic Acid 2.00
Glyceryl Stearate Glyceryl Stearate 5.00
Cetearyl Alcohol Cetearyl Alcohol 3.50
Phase B
Preservative Flakes of Example 1 1.00
Fragrance, Color q.s

Procedure: Phase A is heated at 75 oC with stirring and homogenized for 2 minutes followed by stirring for 15 minutes. It is cooled down to 40° C and then phase B is added and mixed well. It is blended with fragrance and color.