FORM 2
THE PATENTS ACT 1970
(Act 39 of 1970)
&
THE PATENTS RULE, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)
TITLE OF THE INVETION "STABLE PHARMACEUTICAL COMPOSITIONS OF VITAMIN C AND LYSINE"
Zuventus Healthcare Limited an Indian company, registered under the Indian Company's Act 1957 and having its
registered office at
Emcure House, T-184, M.I.D.C., Bhosari, Pune-411026, India.
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED

FIELD OF THE INVENTION
The present invention relates to a stable pharmaceutical composition of vitamin C and lysine in the form of chewable tablet wherein vitamin C comprises a mixture of ascorbic acid, sodium ascorbate and ascorbyl palmitate. The chewable tablet is prepared by non-aqueous wet granulation using ethyl cellulose as a binder.
BACKGROUND OF THE INVENTION
Vitamin C or ascorbic acid is an essential part of daily diet. Vitamin C, is necessary for the growth and development of body tissues. It is a powerful antioxidant and is essential for humans to prevent diseases. Vitamin C helps in formation of collagen as well as in absorption of iron. It aids in the proper functioning of the immune system, wound healing, and maintaining the health of cartilage, bones, and teeth. Compared to other vitamins like vitamin A, vitamin D or vitamin E; vitamin B and vitamin C are highly water soluble thus get easily excreted from the body through urine. Although the body maintains a therapeutic amount of these vitamins, they have to be taken regularly to prevent deficiency. Scurvy, a disease due to deficiency of vitamin C may cause symptoms such as rash, muscle weakness, joint pain, tiredness, or tooth loss.
Vitamin C, also known as ascorbic acid is abundantly available in nature. Ascorbic acid is stable in acidic environment, however in weak acid, neutral and basic environment in the presence of moisture and oxygen, can be easily oxidized to dehydroascorbic acid. This dehydroascorbic acid also has vitamin C properties. In the presence of moisture and elevated temperatures, dehydroascorbic acid gets converted to diketogulonic acid irreversibly, and losses its therapeutic activity. The half-life of vitamin C in aqueous solution is 6 min at 37°c, but the extent of ascorbic acid oxidation to dehydroascorbic acid and its hydrolysis to diketogulonic acid depends on concentration, temperature, pH, light, etc.
Vitamin C is also available in the form of various derivatives like sodium ascorbyl phosphate, magnesium ascorbyl phosphate, sodium ascorbate, calcium ascorbate, and ascorbyl palmitate.

Ascorbyl palmitate is an ester of ascorbic acid and palmitic acid. It has greater fat solubility than ascorbic acid. Sodium ascorbate falls under the category of mineral salts and is more stable when exposed to light and air.
Lysine is an essential amino acid and a precursor to many proteins. Lysine helps to protect against cold sores by blocking arginine. Lysine also helps to reduce anxiety by blocking stress response receptors. It is also known to improve calcium absorption and can promote faster healing of wounds by helping to create collagen in the body. Lysine aids in building a strong and healthy immune system, lowers the risk of infections and inflammation. It is required by human body to maintain good health, but human body cannot produce lysine. Thus we humans are dependent on external sources like food or supplement to fulfil requirement of lysine.
Chewable tablet is an oral dosage form intended to be chewed and then swallowed by the patient rather than swallowed as a whole. These tablets are intended to disintegrate smoothly in mouth at a moderate rate either with or without actual chewing for assimilation in the human body. Characteristically, chewable tablets have a smooth texture upon disintegration, bear a pleasant taste and leave no bitter or unpleasant after taste. Chewable tablet has patient-centric advantage for populations such as paediatrics and geriatrics for whom swallowing of conventional tablets could be a concern.
US 7070804 discloses formulation of chewable tablet comprising: (a) at least one vitamin; (b) at least one mineral selected from the group consisting of: manganese (II) gluconate, copper (II) carbonate, calcium phosphate, ferrous (II) fumarate, zinc oxide, and magnesium oxide, (c) lysine or a pharmaceutically acceptable salt thereof; (d) at least one sweetener, and (e) a pharmaceutically or dietetically acceptable carrier.
US9308178 discloses multilayer microcapsule technique to protect oxidizable active and also to manage release of active. Wherein, it describes protection of vitamin C used as active in different fruit juices with multilayer microcapsulation attained by use of pH dependent water soluble encapsulating agent like sodium alginate, potassium alginate.
WO2022/018630, the inventor discloses rapid melt granules technique to mask the taste of unpalatable molecules by particulate coating comprising the steps of encapsulation of active

ingredient with encapsulation polymer and / or pore former or by complexation. These granules are further filled into sachets or compressed to oral disintegrating tablet.
Ascorbic acid, sodium ascorbate, ascorbyl palmitate and lysine are highly moisture and oxidation sensitive actives. They absorb moisture upon storage which leads to degradation over a period and results in altered physical appearance of tablets. This would also impact the potency of the actives over the shelf life. Moreover, vitamin C is a hydrophilic molecule thus gets readily excreted through urine. Hence it is necessary to maintain the body requirements of vitamin C and lysine, particularly in children and/or elder people to maintain healthy life. Thus the problem underlying current invention was to provide a stable pharmaceutical composition containing vitamin C and lysine.
SUMMARY OF THE INVENTION
The present inventors while working on preparation of chewable tablets of vitamin C and lysine, found that on stability the product degrades leading to discolouration of tablet. Ethyl cellulose being hydrophobic in nature when used as binder in formulation; it has ability of coating the actives present in the tablet. This coating prevented contact of active ingredients with moisture and oxygen thus preventing their discolouration over entire shelf life.
In one of the aspects of the invention, there is provided a stable pharmaceutical composition of vitamin C and lysine in the form of chewable tablet wherein vitamin C comprises a mixture of ascorbic acid, sodium ascorbate and ascorbyl palmitate while lysine is in the form of (L)-lysine hydrochloride. The chewable tablet is prepared by non-aqueous wet granulation using ethyl cellulose as binder.
In another aspect of the invention, there is provided a pharmaceutical composition of vitamin C and (L)-lysine hydrochloride that is stable when stored at 30°C±2°C temp. / 75±5%RH and 40°C±2°C temp./ 75±5%RH over a period of time.
The details of one or more embodiments are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description and claims.

DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed in particular to a stable pharmaceutical composition of vitamin C and lysine in the form of chewable tablet wherein the chewable tablet is prepared by non¬aqueous wet granulation using ethyl cellulose as binder.
In one of the embodiments of the present invention, ethyl cellulose (7cps) is used as a binder. Ethyl cellulose is hydrophobic in nature and has low moisture absorption property. Thus, when added at the granulation stage, ethyl cellulose forms a coat over the actives thereby making a protective barrier layer. This prevents direct contact of active ingredients with the moisture and oxygen thereby improving the formulation stability over entire shelf life.
The pharmaceutical composition of present invention contains vitamin C in the form of ascorbic acid, sodium ascorbate and ascorbyl palmitate.
The total amount of vitamin C in the pharmaceutical composition ranges between 1 mg to 1000 mg, wherein ascorbic acid is about 20 mg to 70 mg; in particular, 50 mg of ascorbic acid, sodium ascorbate is about 100 mg to 600 mg, in particular 450 mg of sodium ascorbate, ascorbyl palmitate is about 50 mg to 250 mg, in particular 120 mg of ascorbyl palmitate per tablet.
Specifically, the subject matter of this invention provides chewable tablets, containing lysine, with vitamin C. Lysine is preferably provided in the form of a pharmaceutically acceptable salt, in particular as (L)-lysine hydrochloride. Most preferably the tablet comprises 1 mg to 10 mg, preferably 5 mg to 8 mg of (L)-lysine hydrochloride per unit.
The present invention provides a stable pharmaceutical composition of vitamin C and lysine in the form of chewable tablet together with one or more pharmaceutically acceptable excipients.
The pharmaceutically acceptable excipients include sweeteners, diluents, glidants, bulking agents, pH modifiers with suitable colorants and flavouring agents.

Examples of suitable diluents include microcrystalline cellulose, lactose, calcium phosphate, starch or combinations thereof.
Examples of suitable glidants include calcium stearate, colloidal silicon dioxide, fumed silica, magnesium stearate, magnesium trisilicate, powdered cellulose, talc or combinations thereof
Examples of suitable sweeteners include aspartame, sucrose, mannitol, sorbitol, or combinations thereof.
Examples of suitable pH modifiers include citric acid, tartaric acid, malic acid or combinations thereof.
In another embodiment of the invention the pharmaceutical composition of vitamin C and (L)-lysine hydrochloride was subjected to storage conditions 30°C±2°C temp. / 75±5%RH for 12 months and 40°C±2°C temp./ 75±5%RH for 6 months and was found to be stable over stability period.
The invention is further explained with the help of following illustrative examples, however, in no way these examples should be construed as limiting the scope of the invention.
EXAMPLES Example-1
Table-1: Chewable tablet formulation

Composition Qty per Tab mg/unit
Ascorbic acid 50
Sodium ascorbate 450
Ascorbyl palmitate 120
(L)-lysine hydrochloride 7.5
Ethyl cellulose 11
Mannitol q.sto 1000
Microcrystalline cellulose 25

Citric acid 50
Colloidal silicone dioxide 10
Magnesium stearate 15
Aspartame 15
Suitable flavour qs
Suitable colour qs
Manufacturing procedure:
The process typically involves mixing ascorbic acid, sodium ascorbate, ascorbyl palmitate and colouring agent. Granulating this mix using ethyl cellulose dissolved in isopropyl alcohol as binder solution. Prepared granules were dried and milled. Remaining excipients were mixed with granules and further lubricated using magnesium stearate as lubricant and compressed into tablets.
Prepared tablets were subjected to stability studies at various storage conditions (Temp. 30°C±2°C and 75±5%RH, Temp. 40°C±2°C and 75±5%RH) evaluated over a period of time and found to be stable over entire stability period. The results are provided in the table below:
Table -2: Stability data at Temp. 30°C±2°C and 75±5%RH

Test Chewable Tablets

Initial 3M 6M 12M
Description Orange colour, circular tabh ;t
Assay
Ascorbic acid & Sodium ascorbate as ascorbic acid 98.15 100.54 99.77 99.35
Ascorbyl Palmitate 99.57 98.65 98.97 96.37
(L)-lysine hydrochloride 111.50 110.24 108.79 108.03
Table -2: Stability data at Temp. 40°C±2°C and 75±5%RH

Test Chewable Tablets

Initial 3M 6M

Description Oran ge colour, circular tablet
Assay
Ascorbic acid & Sodium Ascorbate as Ascorbic acid 98.15 99.60 99.44
Ascorbyl Palmitate 99.57 98.04 97.94
(L)-lysine hydrochloride 111.50 109.88 107.11

I/We Claim ;
1. A stable pharmaceutical composition of vitamin C and (L)-Lysine hydrochloride in the form of chewable tablet wherein, vitamin C comprises a mixture of ascorbic acid, sodium ascorbate and ascorbyl palmitate.
2. The pharmaceutical composition as claimed in claim 1 wherein, the chewable tablet is prepared by non-aqueous wet granulation using elhyl cellulose as binder.