The present invention generally relates to the field of nutritional supplements. The invention, particularly relates to a novel tablet formulation of omega-3-fatty acids and manufacturing process thereof.
(2) BACKGROUND OF THE INVENTION
Omega-3 fatty acids are often referred to as "essential" fatty acids (EFAs) because they are needed for human health but are not sufficiently produced by the body alone. The two major health promoting omega-3 polyunsaturated fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are naturally found in certain cold-water fatty fish such as salmon, tuna, and mackerel. They can also be derived in the body from alpha-linolenic acid (ALA), which is an omega-3 fatty acid found in certain seeds and plant-based oils. However, the body is very inefficient at converting ALA into EPA and DHA.
The modern diet is typically deficient in omega-3 essential fatty acids and has become overloaded with pro-inflammatory omega-6 fatty acids, especially arachidonic acid. This heavy imbalance of omega-6 to omega-3 fatty acids in the modern diet is thought to lead to an overall inflammatory state that contributes to certain diseases. The increased consumption of vegetable oils and shortenings, beef, and dairy is one of the major reasons for the high amount of omega-6 fatty acids in the diet and the imbalance between omega-6 to omega-3 fatty acids. The North American population, in particular, has among the lowest dietary intake of omega-3 fatty acids found in the world and the highest amount of the pro-inflammatory omega-6 fatty acids.

Recent scientific developments have shown that the omega-3 fatty acids, in particular EPA and DHA; play a vital role in central nervous system, cognitive, cardiovascular, joint, immune and metabolic function. EPA and DHA not only protect good overall physical and emotional health, but also can reduce the risk of cardiac disease and exert powerful anti-inflammatory effects that can help treat certain diseases. The benefits of EPA and DHA have been studied across a wide range of illnesses, including, but not limited to heart disease, high cholesterol, hypertension, arthritis, back pain, osteoporosis, psoriasis, lupus, Crohn's Disease, back pain, dry eyes, depression, bipolar disorder, ADHD, and stress-related disorders. Omega-3 fatty acids have also been shown to be important in pregnant women and infants, where their depletion may lead to visual or central nervous system problems.
Adequate amounts of omega 3 fatty acids including EPA and DHA can be obtained in the
diet from cold-water fatty fish such as salmon, tuna, and mackerel. However larger fish
t
species may contain high levels of mercury, polychlorinated biphenyls (PCBs), dioxins or other contaminants. Thus achieving an optimal amount of omega-3 fatty acids through the intake of fish alone raises a number of safety concerns. Fatty acids supplements are available. However, conventional over-the-counter omega-3 fatty acid supplements contain relatively impure material and are typically only about 30% omega 3 fatty acids. This low purity leads to inadequate dosing of essential fatty acids unless a large number of dosage units are consumed each day. Additionally research suggests that the EPA:DHA ratio is important for efficacy. Currently available omega 3 fatty acid preparations, such as the prescription omega-3 medication OMACOR are formulated for cardiovascular use and contain approximately EPA and DHA in an approximately 3:2 ratio. Other omega-3 formulations are intended primarily for treatment of mental health disorders and very high levels of EPA and little or no DHA. The EPA:DHA ratios for these omega-3 formulations is 7:1 or higher. An intermediate ratio EPA:DHA ratio is considered ideal for treatment of a broad range of cardiovascular, autoimmune, inflammatory, and central nervous system disorders. There remains a need for a highly purified omega-3 dosage form having an EPA:DHA ratio of greater than 3:2 and less than 7:1.
There are numerous active substances which are present as liquid oils. Examples of oily active substances having physiological action are unsaturated fatty acids: co-3 and co-6

fatty acids (DHA) poly-unsaturated alcohols: lutein, carotenes (vitamin A) lipophilic phenols and phosphatidylcholines: tocopherols, lecithins plant extracts having a high fat content: evening primrose oil solution of lipophilic active substances in oil. The active-substance-containing oil can be administered only in liquid form.
The active-substance-containing oil can be administered in liquid form. Capsules which hold the oil, primarily gelatine capsules come into consideration here. Such capsules are advantageous since they can be taken easily and slide through the oesophagus without any difficulties. In addition, the active substance in the gelatine shell is protected from light and oxygen. A disadvantage of capsules is the high manufacturing costs.
A number of different types of omega-3-fatty acids formulations are available in the prior art. Prior art document, US7652068 discloses highly purified omega-3 fatty acid formulations. Certain formulations provided herein have contains greater than 85% omega-3.fatty acids by weight. Certain other formulations provided herein contain EPA and DHA in a ratio of from about 4.01:1 to about 5:1. The invention also provides methods of using the dosage forms to treat a variety of cardiovascular, autoimmune, inflammatory, and central nervous system disorders by administering a formulation of the invention to a patient in need thereof.
Another prior art document, WO2015011724 discloses a composition comprising omega-3 fatty acid, a plant extracts at least one surfactant and a process to process to prepare such composition is disclosed. The composition disclosed herein has enhanced bioavailability of omega -3 fatty acids and is substantially free of food effects.
Yet another prior art document, US8828470 discusses a food or beverage composition suitable for human consumption includes an aqueous suspension such as cow's milk that has been supplemented and homogenized with an omega-3 fatty acid-containing supplementation oil, in which a supplementation oil includes one part by weight of an EPA/DHA fatty acid-containing enriching oil that has been combined and diluted.
Yet another prior art document, US20120156296 discloses antioxidants and combinations of antioxidants used to prevent oxidation of pharmaceutical and nutraceutical products in the form of powders, granulates, tablets, emulsions, gels and the like comprising one or

more fatty acids and/or fatty acid derivatives and, optionally, at least one carbohydrate carrier alone or together with vitamins, minerals and/or pharmaceuticals.
Yet another prior art document, US20120107368 describes a compressible tablet material having an oil-containing active substance, tablet as well as method and device for the production thereof. The compressible tablet material includes the following components: oil containing an active substance; silicified microcrystalline cellulose or microcrystalline cellulose as excipient.
However, above mentioned references and many other similar references has one or more of the following shortcomings: (i) disintegration time is higher means dissolves with longer time; (ii) includes many other ingredients; (iii) Also includes excipients such as Microcrystalline cellulose , PVP K 30 , Crospovidone , Mannitol , Talcum , Magnesium stearate , Colloidal silicon dioxide etc. which has longer disintegration time; and (iv) Omega-3-fatty acid formulation is available in liquid forms or in capsule forms.
The present invention fulfills this need and provides related advantages, which are described herein.
(3) SUMMARY OF THE INVENTION
In the view of the foregoing disadvantages inherent in the known types of omega-3-fatty acids formulationsnow present in the prior art, the present invention provides an improvedomega-3-fatty acids. As such, the general purpose of the present invention, which will be described subsequently in greater detail, is to provide a new and improved tablets including omega-3-fatty acids having less disintegration time which has all the advantages of the prior art and none of the disadvantages.
One of the main objective of the present invention is to provide a single dose solid Omega Oil product in the tablet form, the tablet comprising: Omega Oil dry powder; and Excipients

It is another objective of the present invention is to provide the single dose solid Omega Oil product in the tablet form, wherein the Omega oil dry powder contains at least Omega fatty acid 200 mg per unit.
It is another objective of the present invention is to provide the single dose solid Omega Oil product in the tablet form, wherein the tablet contains at least 50 percent of omega oil dry powder.
It is another objective of the present invention is to provide the single dose solid Omega Oil product in the tablet form, wherein the tablet is a fast disintegrating product.
It is another objective of the present invention is to provide the single dose solid Omega Oil product in the tablet form, wherein the tablet contains at least Omega fatty acid dry powder 800 mg per tablet.
It is another objective of the present invention is to provide the single dose solid Omega Oil product in the tablet form, wherein excipients can be selected from the list of Di basic calcium phosphate, Microcrystalline cellulose, Starch, Sodium Lauryl sulphate, Colloidal anhydrous silica, Magnesium stearate, Isopropyl alcohol, Methylene dichloride and many other similar excipients.
It is another objective of the present invention is to provide a preparation method of single dose solid omega oil product in the tablet form, the preparation method comprises the following steps:
a. Dispensing of raw materials, such as omega oil dry powder and excipients;

b. Sifting the raw materials on vibrator sifter of 40 mesh size;
c. Dry mixing of the sifted raw materials;
d. Lubricating the dry mixer with colloidal anhydrous silica and magnesium
stearate;
e. Compressing the lubricated dry mixer;
f. Film coating on the compressed tablet; and
g. Packaging the final tablet.
These together with other objects of the invention, along with the various features of novelty which characterize the invention, are pointed out with particularity in the disclosure. For a better understanding of the invention, its operating advantages and the specific objects attained by its uses, reference should be had to the accompanying drawings and descriptive matter in which there are illustrated preferred embodiments of the invention.
It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-discussed embodiments may be used in combination with each other. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description.
The benefits and advantages which may° be provided by the present invention have been described above with regard to specific embodiments. These benefits and advantages, and any elements or limitations that may cause them to occur or to become more pronounced are not to be construed as critical, required, or essential features of any or all of the embodiments.
While the present invention has been described with reference to particular embodiments, it should be understood that the embodiments are illustrative and that the scope of the

invention -is not limited to these embodiments. Many variations, modifications, additions and improvements to the embodiments described above are possible. It is contemplated that these variations, modifications, additions and improvements fall within the scope of the invention.
(4) DESCRIPTION
In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that the embodiments may be combined, or that other embodiments may be utilized and that structural and logical changes may be made without departing from the spirit and scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims and their equivalents.
The human body can make most of the types of fats it needs from other fats or raw materials. That isn't the case for omega-3 fatty acids (also called omega-3 fats and n-3 fats). These are essential fats—the body can't make them from scratch but must get them from food. Foods high in Omega-3 include fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables.
Omega-3 fats are a key family of polyunsaturated fats. There are three main omega-3s:
• Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) come mainly from fish, so they are sometimes called marine omega-3s.
• Alpha-linolenic acid (ALA), the most common omega-3 fatty acid in most Western diets, is found in vegetable oils and nuts (especially walnuts), flax seeds and flaxseed oil,

leafy vegetables, and some animal fat, especially in grass-fed animals. The human body generally uses ALA for energy, and conversion into EPA and DHA is very limited.
In the present study we are using DHA and ALA (Omega 3 fatty acid). Source of DHA is Alage oil and source of ALA is Flaxseed oil and Pumpkin seed oil.
5 . The active-substance-containing oil can be administered in liquid form. Capsules which
hold the oil, primarily gelatine capsules come into consideration here. Such capsules are advantageous since they can be taken easily and slide through the oesophagus without any difficulties. In addition, the active substance in the gelatine shell is protected from light and oxygen. A disadvantage of capsules is the high manufacturing costs. Consequently
10 endeavours are being made to transfer the oily substance into tablet form. For this purpose
powdery substances are added to the active-substance-containing oil which are intended to absorb the oil. After adding the powdery substance the mixture is pressed into tablets. However, the tablets are of low strength and therefore break very easily. The uniformity of the individual tablets is also unsatisfactory. Finally, it takes a relatively long time before
15 the tablet breaks down in the stomach after it has been taken. Also the absorption of oil in
the powder is not sustainable; over longer periods of time, unmixing of oil and powder take place. It is the object of the invention to provide means or steps by which means a compressible tablet material having an oily active substance can be manufactured and a tablet which can be manufactured from this, which has the requisite properties, i.e. a high
20 content of oily active substance which has the necessary strength, and all the other
properties required of a tablet.
In this study we are preparing tablets (Film coated) containing Algae oil or Flaxssed oil or
combination of both algae oil and flaxseed oil. Tablet contains 50 to 200 mg of oil, either
25 as single oil or in combination.
Normally it is known that when oil is incorporated into tablets, the disintegrating agent losses its characteristic property. However, in the formulation of the present invention, the inventors were able to incorporate Flaxseed oil or alage oil or its combination. Using tablet disintegration apparatus USP (6 units, temperature 37 C , water ) , we have observed
IPO; DELHI 0-4- 16-211* IS 9^#29

disintegrating time less than 3 minutes and 5 minutes for uncoated and coated tablet respectively.
Further, disintegration time was also calculated by putting tablet inside a disintegration test apparatus USP and allowing it to move up and down. Time taken to completely disintegrate was noted.
Initially tablets were prepared using common excipients like microcrystalline cellulose, PVP K-30, Crospovidone, Mannitol, Talcum, Magnesium stearate, Colloidal silicon dioxide etc. Both direct compression method and wet granulation process were tried. Disintegration time was observed to be more than 60 minutes. Further a combination of different super disintegrating agent like Cros povidone XL, cros carmellose sodium, Resin, L Hydroxy propyl cellulose etc were tried to improve disintegration of tablets . Using about 20 % ( of tablet weight) of super disintegrating agent, disintegration time was observed to be about 35 to 45 minutes ( more than pharmacopeal limit).
Finally the formulation in discussion was prepared using wet granulation technique using combination of excipients like microcrystalline cellulose, sodium caseinate, calcium caseinate, starch, PVP K-30, cros carmellose sodium, Mannitol, Talcum, Magnesium stearate and Colloidal silicon dioxide . It was observed that disintegrating time is less than 3 minutes and 5 minutes for uncoated and coated tablet respectively.
The primary goals of the development were to formulate a fast disintegrating single dose solid Omega Oil product containing Omega fatty acid at a concentration of not less than 200 mg per unit that could be easily manufactured, that would be stable in Blister packs.
Composition:
Each film coated tablet contains:
Omega Oil powder (50%) 800 mg

Excipients

q.s

Components of the Omega Oil Product
1. Omega Oil substance
Omega-3 fatty acids—also called co-3 fatty acids or n-3 fatty acids are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. The fatty acids have two ends, the carboxylic acid (-COOH) end, which is considered the beginning of the chain, thus "alpha", and the methyl (-CH3) end, which is considered the "tail" of the chain, thus "omega"; the double bond is at omega minus 3 (not dash 3). One way in which a fatty acid is named is determined by the location of the first double bond, counted from the methyl end, that is, the omega (co-) or the n- end. However, the standard (IUPAC) chemical nomenclature system starts from the carboxyl end.
The three types of omega-3 fatty acids involved in human physiology are a-linolenic acid (ALA) (found in plant oils), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (both commonly found in marine oils). Marine algae and phytoplankton are primary sources of omega-3 fatty acids. Common sources of plant oils containing the omega-3 ALA fatty acid include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega-3 EPA and DHA fatty acids include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and kxill oil. Dietary supplementation with omega-3 fatty acids does not appear to affect the risk of death, cancer or heart disease. Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.
Omega-3 fatty acids are important for normal metabolism. Mammals are unable to synthesize omega-3 fatty acids, but can obtain the shorter-chain omega-3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega-3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the

most crucial, DHA (22 carbons and 6 double bonds). The ability to make the longer-chain omega-3 fatty acids from ALA may be impaired in aging. In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity
2. Omega Oil Dry Powder
Omega Oil dry powder is manufactured in house using spray drying process, using sodium caseinate as encapsulating material and Maltodextrin as base material, along with emulsifmg agents. Omega Oil powder contains 50% Omega oil, which is free flowing powder containing encapsulated oil, which protects Omega from oxidation and rancidity.
3. Excipients
The known and commonly used tablet excipients have been selected from the group consists of Di basic calcium phosphate DC, Microcrystalline cellulose PHI 12, Pregelatinized starch, Maize Starch, Sodium lauryl sulphate, Magnesium stearate, Colloidal anhydrous silica, Opadry OY-S-29019 Clear or Opadry white 21K580004.
3.10mega Oil-Excipient Compatibility Study
The blends of the Omega Oil powder and commonly used GRAS excipients were subjected to accelerated conditions of temperature and humidity viz; 30°C ± 2°C / 75 %RH ± 5% RH and 40°C ± 2°C / 75 %RH ± 5% RH to evaluate the compatibility. Mixtures were kept in hermetically sealed clear glass vials.
Observations Result:
1) Aat 30°C ± 2°C / 75 %RH ± 5% RH, the dry Mix of all the excipients along with the Omega Oil powder(50%), did not show any change up to 2 months,

2) At 40°C ± 2°C / 75%RH ± 5% RH, the dry Mix of all the excipients along with the Omega Oil powder(50%), did not show any change up to 2 months.
1. No significant change (both Physical and Chemical) occurs in the samples of Dry Mix of Omega Oil powder and Excipients, storing at 40°C ± 2°C / 75%RH ± 5% RH upto 2 months.
2. In addition to the results of the study, it may be noted that the development batches stability has established the compatibility of the excipients with Omega Oil powder and the formal stability studies undertaken on the validation batches would has establish them to be compatible with Omega Oil powder(50%) over the proposed shelf life of the product.
Example 1: Omega Oil Product
Analytical Development
Omega Oil powder is not official in Indian Pharmacopoeia. Hence, in house method was developed and was adopted for analysis of both Omega Oil powder and Omega tablet.
Formulation Development
The objective of the development programme was to formulate a robust, stable formulation of Omega tablet using Omega Oil powder (50%).
Formulation development trials
Based on the literature review, the following strategy was adopted for development work.
In house development and manufacturing of Omega Oil powder(50%). Manufacturing process development and optimization of Omega tablets. The preferred primary pack is Blister pack.

The development studies were undertaken as per the strategy. In the development stage, lab scale batches were prepared and evaluated to arrive at a prototype formula and tentative process for trial batches.
Based on the performance of lab scale batches, specifications for both Omega Oil powder and Omega tablet are finalized for scale up/exhibit batch activities.
Brief manufacturing process
1. Omega tablets were prepared following the below mentioned process:
a) Omega Oil powder(50%), Di basic calcium phosphate, Microcrystalline cellulose, Maize starch, Sodium lauryl sulphate and Pregelatinized starch , were passed through 40 #, and mixed in blender for 10 minutes.
b) The above blend was lubricated with pre sifted colloidal anhydrous silica (40 #) for 10 minutes followed by pre sifted Magnesium Stearate (40 #) for 2 minutes.

2. Further blend for Omega tablets was compressed using oblonged shaped biconcave punch, to prepare Omega tablets.
3. Then film coated separately, to get film coated tablets
4. Film coated tablets were packed into blister pack (PVC blister pack)
Initial feasibility trials:
Initially a blend was prepared based on literature data. This bend was compressed into Omega tablets (Batch No DS061130201). These core tablets were further film coated to get film coated Omega tablets. In-vitro evaluation studies of these tablets (i.e. Omega tablets Batch No DS061130201) showed satisfactory physico-chemical properties. The details data and. batch composition has been given in below table No 1.
Table No 1: Summary of Composition and Physicochemical Data for trial batches of Omega tablets

Batch No.

DS061130201

Batch Size 5000 tablets
Composition Mg/ tablet
Dry mix
1 Omega Oil powder(50%) 800.00
2 Di basic calcium phosphate DC 174.00
3 Maize starch • 50.00
4 Sodium lauryl sulphate 30.00
5 Microcrystalline cellulose PHI 12 167.00
6 Pre gelatinized starch 14.00
Lubricant.
Magnesium Stearate 12.00
Colloidal anhydrous silica 12.00
Core weight 1259.00
Film coat
Opadry OY-S-29019 Clear 36.00
Isopropyl alcohol • Qs
Methylene dichloride Qs
Coated Tablet Weight 1295
Physical Parameters^-v ' • '\Kv\'- -X'*^--'
Thickness (mm) H
Hardness (Kg/cm2) Core tablets 9-12
Disintegration Time at 37°C (minutes) 20.0
N" >'v^ss%l(^r^p^^ •-; ^:^ 98.0
Optimization of Disintegrate quantity
To optimize the quantity of disintegrant in the formulation, Omega tablets were prepared with 50 % more and 50 % less disintegrant (Pregelatinized starch) Batch No DS061130202A and DS061130202B respectively. The physico-chemical evaluation data

shows that change in 10% disintegrant in the formulation has significant effect in the formulation. The details of batch data are given in Table No 2.
Table No 2: Summary of Composition and Physicochemical Data for trial batches of Omega tablets

Xpt;N6i.;.'';.;;..;' . DS061130202 A DS061130202B
Batch Size 5000 tablets 5000 tablets
Composition Mg/tablets Mg/tablets
Dry mix
Omega Oil powder(50%) 800.00 800.00
Di basic calcium phosphate DC 206.00 167.00
Maize starch 50.00 75.00
Sodium lauryl sulphate 30.00 30.00
Macrocrystalline cellulose PHI 12 167.00 167.00
Pregelatinized starch 7.00 21.00
Lubricant
Magnesium Stearate 12.00 12.00
Colloidal anhydrous silica 12.00 12.00
Core weight 1284.00 1284.00
Film coat
Opadry OY-S-29G19 Clear 36.00 36.00
Isopropyl alcohol Qs Qs
Methylene dichloride Qs Qs
Coated Tablet Weight 1320.00 1320.00
"'•' ■•' 'Phy'sical'Para'ihete>sv:"N':i■:(''■•''-';:'-. '.v.- '■-;;,-:' ;- ".'\''';:.
Thickness (mm) 7.8 7.8
Hardness (Kg/cm2) core tablets 8-11 8-11
Disintegration Time at 37°C (minutes) 45.0 1.20
Optimization of Lubricant quantity
EL/tf-i: O4rl0- 2'-fc*'3$-8>-- l-t>-- %§ 0f 29

To optimize the quantity of Lubricant in the formulation Omega tablets were prepared
with 50% Magnesium stearate and without Colloidal anhydrous silica Batch No
DS061130202C and DS061130202D respectively. The physico-chemical evaluation data
shows that batch with 50 % Magnesium stearate in the formulation showed slight
5 sticking. However, in formulation without Colloidal anhydrous silica showed sticking.
The details of batch data are given in Table No 3.
Table No 3: Summary of Composition and Physicochemical Data for trial batches of Omega tablets

Batch No. DS061130202C DS061130202 D
Batch Size 5000 tablets 5000 tablets
Composition Mg/tablets Mg/tablets
Dry mix
Omega Oil powder(50%) 800.00 800.00
Di basic calcium phosphate DC 167.00 167.00
Microcrystalline cellulose PHI 12 167.00 167.00
Maize starch 75.00 75.00
Sodium lauryl sulphate 30.00 30.00
Pregelatinized starch 21.00 21.00
Lubricant
Magnesium Stearate 6.00 24.00
Colloidal anhydrous silica 12.00 0.00
Core weight 1278 1284
Final coat
Opadry OY-S-29019 Clear 36.00 36.00
Isopropyl alcohol Qs
} Qs
Methylene dichloride Qs Qs
Coated Tablet Weight 1314 1320
Physical Parameters
y E L'B I u 4 - I U-- 2.u■ I 8 11> : 4i$ 0f 29

Thickness (mm) 7.8 7.8
Hardness (Kg/cm2) core tablets 8-11 8-11
Disintegration Time at 37°C (minutes) 1.40 1.0
Optimization of weight gain in coating
To optimize the coating material quantity in the final formulations, two batches Omega
tablets were prepared. Batch No DS061130202E was prepared by coating core tablets
with 2% coating material (Film coat). Batch No DS061130202F was prepared by coating
5 core tablets with 4% coating material (Film coat). Omega tablets Batch No
DS061130202E, showed non-uniform coating. However, coating of Batch No DS061130202F was satisfactory. Physico-chemical evaluation data of both batches were observed to satisfactory (Table No 4).
Table No 4: Summary of Composition and Physicochemical Data for trial batches of
10 Omega tablets

Batch No. DS061130202E DS061130202F
Batch Size 5000 tablets 5000 tablets
Composition Mg/tablets Mg/tablets
Dry mix
Omega Oil powder(50%) 800.00 800.00
Di basic calcium phosphate DC 167.00 167.00
Microcrystalline cellulose PHI 12 167.00 167.00
Maize Starch 75.00 75.00
Sodium Lauryl sulphate 30.00 30.00
Pregelatinized starch 21.00 21.00
Lubricant
Magnesium Stearate 12.00 12.00
Colloidal anhydrous silica 12.00 12.00
Core weight 1284.00 1284.00
Film coat
Opadry OY-S-29019 Clear 24.00 60.00
Isopropyl alcohol q.s Qs
-LP u Dfc LHi u 4 - I O - 2 01 8 i 6 : 4 U8 of 29

Methylene dichloride Qs Qs
Coated Tablet Weight 1308 1344
Physical Parameters
Thickness (mm) 7.8 7.8
Hardness (Kg/cm2) Core tablets 9-12 9-12
Disintegration Time at 37°C (minutes) 1.09 1.45
Formulation Stability study
Three reproducible batches (Batch No DS061130203, DS061130204 and DS061130205)
were prepared. All the batches were packed into strip packs. These packed tables were then charged on stability .The details of physico-chemical evaluation data these batches has been given in the following Table No 5.a
Table No 5.a: Summary of Composition and Physicochemical Data for trial batches of Omega tablets

Batch No. DS061130203 DS061130204 DS06113020
5
Batch Size 5000 tablets 5000 tablets 5000 tablets
Composition Mg/tablet Mg/tablet Mg/tablet
Dry mix
Omega Oil powder(50%) 800.00 800.00 800.00
Di basic calcium phosphate DC 167.00 167.00 167.00
Microcrystalline cellulose PH112 167.00 167.00 167.00
Maize Starch 75.00 75.00 75.00
Sodium Lauryl sulphate 30.00 30.00 30.00
Pregelatinized starch 21.00 21.00 21.00
Lubricant
Magnesium Stearate 12.00 12.00 12.00
Colloidal anhydrous silica 12.00 12.00 12.00
Core weight 1284 1284 1284

Film coat
Opadry OY-S-29019 Clear O.Sp. 36.00 36.00 36.00
Isopropyl alcohol Qs Qs Qs
Methylene dichloride Qs Qs Qs
Coated Tablet Weight 1320 1320 1320
Physical Parameters
Thickness (mm) 4.70±0.2 4.70+0.2 4.70±0.2
Hardness (Kg/cm ) core tablet 4.0-6.0 4.0-6.0 4.0-6.0
Disintegration Time at 37°C (minutes) 1.50 1.0 1.10
Process reproducibility studies
Three reproducible batches (Batch No DS061140606, DS061140607 and DS061140608)
were prepared. Tablets are film coated with Opadry 21K580004 and all the batches were
packed into PVC blister packs..The details of physico-chemical evaluation data these
5 batches has been given in the following Table No 5.b. . •
Table No 5.b: Summary of Composition and Physicochemical Data for trial batches of Omega tablets

Batch No, DS061140606 DS061140607 DS06114060 8
Batch Size 10,000 tablets 10,000 tablets 10,000 tablets
Composition mg/tablet mg/tablet mg/tablet
Dry mix
Omega Oil powder(50%) 800.00 800.00 800.00
Di basic calcium phosphate DC 167.00 167.00 167.00
Microcrystalline cellulose PH112 167.00 167.00 167.00
Maize Starch 75.00 75.00 75.00
Ut'LHI U-4'T 10 -2BM-8.- 16 : 42§ 0f 29

Sodium Lauryl sulphate ' 30.00 30.00 30.00
Pregelatinized starch 21.00 21.00 21.00
Lubricant
Magnesium Stearate VG 12.00 12.00 12.00
Colloidal anhydrous silica 12.00 12.00 12.00
Core weight 1284 1284 1284
Film coat
Opadry White 21K580004 36.00 36.00 36.00
Isopropyl alcohol Qs Qs Qs
Methylene dichloride Qs Qs Qs
Coated Tablet Weight 1320 1320 1320
/■V'TWysicai-'^ra'm.e^
Thickness (mm) 4.50+0.2 4.50+0.2 4.50+0.2
Hardness (Kg/cm2) core tablet 4.0-6.0 4.0-6.0 4.0-6.0
Disintegration Time at 37°C (minutes) 1.50 1.0 1.10
Accelerated Stability Trial
Batch Nos. DS062140605 , DS062140606 and DS062140607 Of Omega tablets were packed in strip packs and placed on stability at 40°C/75%RH and 30°C/65%RH. Chemical results from Stability tests are summarized in Table No 6.
5 Table No. 6Stability Data Omega tablets

Product name OMEGA TABLETS Stability Initiated On 12/01/20 17 Mfg. Date Janua 2017 Data
Presente
d 20/07/ 2017
Batch No. DS062140605 Batch Size 10,000 Tablets Durat ion 6 Month
Packing Details PVC blister packing 1X10 Test Method IP STP
No. RD/STP/SEN/081
Storage Condition 40°C±2°C/75% RH±5% Stability Protocol No. RD/SSP/ 071-00 Spec
No. RD/SPEC/SEN/158 '
PW utL WI 0 4--IO- 2-& 1-g. I 6 : 42i of 29

ACCELERATED STABILITY STUDY (40°C±2°C/75% RH±5%)
Time Interval Initial 1 Month 2 Month 3 Month 6 Month Remark
s
Pull out date
12/01/2 017 14/02/20 17 14/03/20 17 15/04/20 17 16/07/20 17

Analysis Date
12/01/2 017 14/02/20 17 14/03/20 17 15/04/20 17 16/07/20 17

S.
N
0 Test Specification ANALYTICAL REFERENCE NUMBER

RD/AR/ SS/17/0 25 RD/AR/
SS/17/03 4 RD/AR/ SS/17/0 40 RD/AR7
SS/17/0 54 RD/AR/
SS/17/09 4

1 Description Light brown colour, Oblong shaped, slightly biconvex, film coated tablets, plain on both side. Light
brown
colour,
Oblong
shaped,
slightly
biconvex,
film
coated
tablets,
plain on
both side. Light
brown
colour,
Oblong
shaped,
slightly
biconvex,
film
coated
tablets,
plain on
both side. Light
brown
colour,
Oblong
shaped,
slightly
biconvex,
film
coated
tablets,
plain on
both side. Light
brown
colour,
Oblong
shaped,
slightly
biconvex,
film
coated
tablets,
plain on
both side. Light
brown
colour,
Oblong
shaped,
slightly
biconvex,
film
coated
tablets,
plain on
both side. Complie s
2 Identification

A. By GC The principal peak in the chromatogram obtained with the sample solution is concordant with the retention Complie
s Complies Complie
s Complie s Complie
s Complie s
U UtLHI 0 4 - 1 6 - ZBi.B 16 : 422 of 29

time to the principal peak in the
chromatogram obtained with the standard solution.
3 Average weight
(mg) 1320.00±5% 1318.2 1318.2 1318.6 1318.6 315.4 Complie s
4 Disintegratio n time (minutes) Not more than 30 1 min 47 sec 1 min 56 sec 1 min 49 sec 1 min 45 sec lmin48 sec Complie
s
5 Loss on
drying
(%w/w) Not more 6.0 4.7 4.7 4.9 4.8 4.8 Complies
6 OMEGA 3
Assay by GC (%w/w) Not less than 85.0 and
Not more thanll5.0 97.4 98.2 98,6 91.4 89.3 Complie
s
Observation: No significant change observed.
Conclusion: Stability data of DS062140605 , DS062140606 and DS062140607 of
Omega tablets were packed in strip packs, indicated that the formulation of Omega
tablets are both physically and chemically stable at 40°C/75%RH for a period of 6
5 months.
Example 2
Final Formulation and Manufacturing Process
O- DELHI 04-10-2018 16 : 4jf of 29

Based on the above development data, the finalized formulation is as follows:-
Table No 7: Final Formulation Details

Ingredient UNIT FORMULA
(mg/tablet) 1IC limit
Omega Tablets
Omega Oil powder(50%) 800.00 NA
Di basic calcium phosphate DC 167.00 525.56 MG
Microcrystalline cellulose PHI 12 167.00 530MG
Maize Starch 75.00 180MG
Sodium Lauryl sulphate 30.00
Pregelatinized starch 21.00
Colloidal anhydrous silica 12.00 33 MG
Magnesium stearate 12.00 28.31M G
Opadry 21K580004 36.00 30MG
Isopropyl alcohol * q.s
Methylene dichloride * q.s
Core Mass (mg) 1284.00
Coated Tablet Mass (mg) 1320.00

Final Manufacturing Process
5 The flow chart for manufacturing process finalised for the above formulation is
follows:
Process Flow Chart for manufacturing operations is given below

2- W: I &

i-t> : <5'&4 of 29

PROCESS
DISPENSING OF RAW MATERIAL
U

Omega Oil powder(50%) (#40),
Di basic calcium Phosphate DC, (#40) ,
Microcrystalline cellulose PH112 ( #40),
Pregelatinized starch (# 40)
Maize starch (# 40)
Sodium Lauryl sulphate (# 40)

SIFTING ( On vibratory sifter)
T
DRY MIXING (IPC blender )
IT

Colloidal anhydrous silica, [sifted through #
40]
Magnesium Stearate [sifted through #40]

LUBRICATION
(IPC Blender )

T
COMPRESSION
(Compression Machine)
U

PREPARTION OF FINAL COATING DISPERSION
[Opadry , Isopropyl alcohol and Methylene
dichloride ]
Note :
Mesh 20 is equivalent to 850ja , Mesh 40 is equivalent to
425 n , Mesh 60 is equivalent to 250 \i.

FILM COATING
U
PACKAGING PVC blister

Note: Maintain temperature NMT 25°C and relative humidity of NMT 50% throughout the manufacturing process.
Overages
No overages are used in Omega tablets.
Physiochemical and Biological Properties
Indications and Usage: Supplementation of Omega
Contraindications: Nausea, vomiting, or other symptoms of appendicitis; acute surgical abdomen; fecal impaction; intestinal obstruction; undiagnosed abdominal pain
Manufacturing Process Development

-L fc± *l - 1-

Z UiS I

of 29

A direct compression process has been developed for manufacturing of Omega
tablets.Accelerated stability study data found to be satisfactory. The accelerated stability
results of assay, related substance were found to be almost comparable with the initial
results. Considering the available stability data and the shelf life of for the innovator
5 product, reasonably a tentative shelf life of 24 months is proposed to our product in PVC
blister pack. The proposed shelf life will be verified through stability of validation batches.
Based on the satisfactory product and process parameters and the available accelerated
stability data, the same composition and process is proposed for commercial batches of
10 Omega tablets.
Container Closure System
Omega Tablets are packed as detailed below.
The film coated tablets are packed in blisters consisting of a clear, transparent PVC film
(250|i), which is heat-sealed to a Plain Aluminium foil (25|i).The stability data shows that
15 this kind of packaging provides adequate protection to the product. The same pack will be
used for the commercial product.
Microbiological Attributes
Omega tablets comply with microbiological requirements of LP. which are applicable to
preparations for oral use. Compliance with the specification is controlled in the scope of
20 batch release.
Compatibility
Omega Film Coated Tablets are intended for oral use without being dissolved or reconstituted prior to administration. Therefore, the aspect of compatibility is not applicable.
25
It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-discussed embodiments may be used in combination
DEL K I' 04~ I O - 2@: IS 15 > 4»jp f 2Q

with each other. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description.
The benefits and advantages which may be provided by the present invention have been described above with regard to specific embodiments. These benefits and advantages, and any elements or limitations that may cause them to occur or to become more pronounced are not to be construed as critical, required, or essential features of any or all of the embodiments.
While the present invention has been described with reference to particular embodiments, it should be understood that the embodiments are illustrative and that the scope of the invention is not limited to these embodiments. Many variations, modifications, additions and improvements to the embodiments described above are possible. It is contemplated that these variations, modifications, additions and improvements fall within the scope of the invention.

CLAIMS:

A single dose solid Omega Oilproduct in the tablet form, the tablet comprising:
Omega Oil dry powder; and
Excipients
The single dose solid Omega Oil product in the tablet form according to claim 1, wherein the Omega oil dry powder contains at least Omega fatty acid 200 mg per unit.
The single dose solid Omega Oil product in the tablet form according to claim 1, wherein the tablet contains at least 50 percent of omega oil dry powder.
The single dose solid Omega Oil product in the tablet form according to claim 1, wherein the tablet is a fast disintegrating product.
The single dose solid Omega Oil product in the tablet form according to claim 1, wherein the tablet contains at least Omega fatty acid dry powder 800 mg per tablet.
The single dose solid Omega Oil product in the tablet form according to claim 1, wherein excipients can be selected from the list of Di basic calcium phosphate, Microcrystalline cellulose, Starch, Sodium Lauryl sulphate, Colloidal anhydrous silica, Magnesium stearate, Isopropyl alcohol, Methylene dichloride and many other similar excipients.
A preparation method of single dose solid omega oil product in the tablet form, the preparation method comprises the following steps:
h. Dispensing of raw materials, such as omega oil dry powder and excipients; i. Sifting the raw materials on vibrator sifter of 40 mesh size; j. Dry mixing of the sifted raw materials;

k. Lubricating the dry mixer with colloidal anhydrous silica and magnesium
stearate; 1. Compressing the lubricated dry mixer; m. Film coating on the compressed tablet; and n. Packaging the final tablet.