DESC:FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)

1.Title of the invention – A NOVEL RAFT FORMING TABLET FORMULATION OF DAHLIA PINNATA EXTRACT
2. Applicant(s)
NAME: R K University
NATIONALITY: INDIAN
ADDRESS: R K University, School of Pharmacy, Bhavnagar Highway, Tramba, Rajkot-360020, Gujrat, India

3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner
in which it is to be performed.

A NOVEL RAFT FORMING TABLET FORMULATION OF DAHLIA PINNATA EXTRACT

FIELD OF THE INVENTION¬¬
The present invention relates to a novel raft forming tablet formulation of dahlia pinnata extract. The present invention is also relates to a raft forming tablet formulation of dahlia pinnata extract comprising methanolic extract of dahlia pinnata, two raft forming agents, binder, sweetener, lubricant, glidant, two gastric acid and vehicle. The present invention relates to processing steps of preparing the novel raft forming tablet formulation of dahlia pinnata extract. The formulation also offers the potential for the treatment of gastric ulcer.

BACKGROUND OF THE INVENTION
Gastric ulcer is the most common disease which is seen in every age group of patients. Gastric ulcers, are painful sores in the stomach lining. Stomach ulcers are a type of peptic ulcer disease. Peptic ulcers affects both the stomach and small intestines. Ulcer is a gastrointestinal inflammatory disease which is caused by various reasons, which are high dose of NSAIDs (non-steroidal anti-inflammatory drugs), H. pylori infection, excessive consumption of alcohol and tobacco etc.

In gastric ulcer, lesions has been observed on the stomach wall. When gastric acid comes in contact with the lesions the inflammation has been produced sometimes, internal bleeding also takes place and bloody diarrhea has been observed as a symptoms of the gastric ulcer.

Stomach ulcers may be easily cured, but they can become severe without proper treatment. There are many allopathic medicines are available for the treatment of gastric ulcer diseases like pantoprazole, omeprazole and lansoprazole etc. Allopathic medicine only exerts limited ability to recover from gastric ulcer and the long term use of allopathic medication lead to side effects and exhibit less therapeutic effect.
Alternatively, the herbal remedy has gained more attraction and useful because, herbal treatments are more effective, safe and have a less side effects. Traditionally, medicinal plant are being used for the treatment of gastric ulcer. No herbal formulation for the treatment of gastric ulcer is available in the market. There is a requisite and desire for the therapeutic agent and/or treatment protocol to overcome the complications and side effects of existing treatments, which is easy to manufacture, safe and effective bioavailable formulation.

To overcome above problems, Raft forming tablet is a novel approach to handle the problems related to the gastric region of the gastro intestinal tract by gastro retentive drug delivery system. Here raft of polymer will float on the surface of the gastric acid and it will show a release of the incorporated drug.

In the present invention the inventor has focused on providing certain advantages over conventional formulations such as easy to manufacture, not as much of expensive and effective herbal formulation without increase in side effects for the treatment of gastric ulcer.

Therefore, here in the present invention, the inventors surprisingly found that the present invention can overcome the above stated problems associated with the existing treatment, which is a novel drug delivery approach of herbal extract with other pharmaceutically acceptable ingredients.

OBJECTIVE OF THE INVENTION
The main object of the present invention is to provide a novel raft forming tablet formulation of dahlia pinnata extract.

The other object of the present invention is provide a novel raft forming tablet formulation of dahlia pinnata extract which is safe and enhanced effectiveness.
One more object of the present invention is to provide a novel raft forming tablet formulation of dahlia pinnata extract which is stable.

Another object of the present invention is to provide a novel raft forming tablet formulation of dahlia pinnata extract which is having better patient compliance and therapeutic efficacy.

Other main object of the present invention is to provide a novel raft forming tablet formulation of dahlia pinnata extract which can be used in the treatment of gastric ulcer diseases and useful for people of age 10-80 year.

SUMMARY OF THE INVENTION
The main aspect of the present invention is to a novel raft forming tablet formulation of dahlia pinnata extract.

The main aspect of the present invention is to provide the novel raft forming tablet formulation of dahlia pinnata extract comprising methanolic extract of dahlia pinnata, two raft forming agents, binder, sweetener, lubricant, glidant, two gastric acid and vehicle.

Another aspect of the present invention is to provide the novel raft forming tablet formulation of dahlia pinnata extract and a process for preparing the same.

One more aspect of the present invention is to provide the novel raft forming tablet formulation of dahlia pinnata extract which is useful for the treatment of gastric ulcer.

DETAILED DESCRIPTION OF THE INVENTION
The present invention is all about a novel raft forming tablet formulation of dahlia pinnata extract.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described.

As used herein, the term "formulation" or “composition” and derivatives thereof, unless otherwise defined refers to solid oral pharmaceutical dosage forms of the invention that contain active ingredient and pharmaceutically acceptable salts thereof.

As used herein, “raft forming tablet” means, in the presence of gastric acid, the bicarbonate is converted to carbon dioxide, which becomes entrapped within the gel precipitate, converting it into foam, which floats on the surface of the gastric contents. The raft-forming formulation requires gastric acid such as sodium or potassium bicarbonate.

As used herein, whether in a transitional phrase or in the body of a claim, the terms “comprise(s)” and “comprising” are to be interpreted as having an open-ended meaning. That is, the terms are to be interpreted synonymously with the phrases “having at least” or “including at least”. When used in the context of a process, the term “comprising” means that the process includes at least the recited steps, but may include additional steps. When used in the context of a composition, the term “comprising” means that the composition includes at least the recited features or components, but may also include additional features or components.

As used herein, the singular forms “a,” “an” and “the” specifically also encompass the plural forms of the terms to which they refer, unless the content clearly dictates otherwise.

The term “about” is used herein to means approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term “about” or “approximately” is used herein to modify a numerical value above and below the stated value by a variance of 20%.

The main embodiment of the present invention is to provide the novel raft forming tablet formulation of dahlia pinnata extract comprising methanolic extract of dahlia pinnata, two raft forming agents, binder, sweetener, lubricant, glidant, two gastric acid and vehicle.

Methanolic extract of dahlia pinnata:
Dahlia pinnata plant was procured from Ira nursery, Rajkot, Gujarat and the certificate of authentication was provided by Botany department of christ college, Rajkot.

Dahlia pinnata is a species in the genus Dahlia pinnata, family Asteraceae, with the common name garden dahlia pinnata. It is the type species of the genus and is widely cultivated. Dahlia pinnata contains some chemical constituents like butein & inulin which possess anti-ulcer activity as well as anti-microbial activity to prevent H. pylori infection.

As per one embodiment, the method of extraction of dahlia pinnata comprises the steps of,
(a) drying the whole Dahlia pinnata plant under the shade;
(b) grounding the whole plant into a fine powder;
(c) adding twice quantity of the methanol in to the powder and keeping it for 24 hr;
(d) sieving and concentrating the methanol and collecting the extracts of Dahlia pinnata.

As per one embodiment the Dahlia pinnata can be present in the composition in the range from 1 to 200 gm, preferably 1 to 150 gm, more preferably 1 to 100 gm, most preferably 1 to 80 gm. In a most preferred embodiment the Dahlia pinnata is present in the range from 1 to 50 gm.

As per one embodiment, raft forming agents are a substance which have an ability to form a gelatinous viscous layer on contact with the acidic gastric content or which can maintain their viscous structure in presence of acidic gastric content, if formed already. Edible raft forming agents are commonly used to thicken sauces, soups, and puddings without altering their taste; raft forming agents are also used in paints, inks, explosives, and cosmetics.

As per one embodiment, the present invention contains one or more raft forming agent, preferably combination of two raft forming agents.

As per one embodiment, raft forming agents are selected from sodium alginate, gelatin, pectin, xanthan gum, cellulose, cornstarch, agar-agar, pregelatinized starches, arrowroot and potassium alginate. Most preferably raft forming agents are combination of sodium alginate and pectin.

As per one embodiment, raft forming agents can be present in the composition in the range from 1 to 200 gm, preferably 1 to 150 gm, more preferably 1 to 100 gm, most preferably 1 to 50 gm. In a most preferred embodiment the raft forming agents are present in the range from 1 to 20 gm.

As per one embodiement, the binders are used to turn powder to granules; this is achieved through the process of granulation. During granulation, powder substances are accumulated to form larger particles called granules. Binders ensure that tablets, powders, granules and others can be formed with the required mechanical strength.

As per one embodiement of the present invention, binder is selected from but not limited to group consisting of PVP K30, HPMC E50 LV, HPMC K100M, (Poly ethylene glycol) PEG 6000 and Eudragit RL 100. Most preferably the binder is HPMC K100M.

As per one embodiment the binder can be present in the composition in the range from 1 to 50 gm, preferably 1 to 40 gm, more preferably 1 to 20 gm, most preferably 1 to 10 gm. In a most preferred embodiment the binder is present in the range from 1 to 5 gm.

As per one embodiement, the lubricant is a substance that helps to reduce friction between surfaces in mutual contact, which ultimately reduces the heat generated when the surfaces move. It may also have the function of transmitting forces, transporting foreign particles, or heating or cooling the surfaces. The property of reducing friction is known as lubricity.

As per one embodiement of the present invention, lubricant is selected from but not limited to group consisting of are microcrystalline cellulose, magnesium stearate, castor oil, olive oil, polytetrafluoroethylene, boron nitride, lanolin and palm oil. Most preferably the lubricant is magnesium stearate.

As per one embodiment the lubricant can be present in the composition in the range from 1 to 40 gm, preferably 1 to 30 gm, more preferably 1 to 20 gm, most preferably 1 to 10 gm. In a most preferred embodiment the lubricant is present in the range from 1 to 5 gm.

As per one embodiement, the glidant is a substance that is added to a powder to improve its flowability. A glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flowability.

As per one embodiement of the present invention, glidant is selected from but not limited to group consisting of starch, colloidal silicon dioxide, calcium palmitate and talc. Most preferably glidant is talc.

As per one embodiment the glidant can be present in the composition in the range from 1 to 40 gm, preferably 1 to 30 gm, more preferably 1 to 20 gm, most preferably 1 to 10 gm. In a most preferred embodiment the glidant is present in the range from 1 to 5 gm.

As per one embodiment, Sweetening agents are excipients often added to pharmaceutical dosage forms to mask bitter taste of the partially dissolved drug and to improve palatability in general.

As per one embodiment, sweetener is selected from Aspartame, sucralose, saccharin, honey, stevia, alitame and cyclamates. Most preferably sweetener is aspartame.

As per one embodiment the sweetener can be present in the composition in the range from 1 to 40 gm, preferably 1 to 30 gm, more preferably 1 to 20 gm, most preferably 1 to 10 gm. In a most preferred embodiment the sweetener is present in the range from 1 to 5 gm.

As per one embodiment, vehicle is a carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered.

As per one embodiment, vehicle is selected from purified water, mannitol, poly ethylene glycol, xylene, benzene, toluene, glycerin, propylene glycol and benzyl alcohol. Most preferably vehicle is mannitol.

As per one embodiment, gastric acid kills ingested microorganisms and limits bacterial growth in the stomach and prevents intestinal infections. In the present invention, in the presence of gastric acid, the bicarbonate is converted to carbon dioxide, which becomes entrapped within the gel precipitate, converting it into foam, which floats on the surface of the gastric contents. The raft-forming formulation requires gastric acid such as sodium or potassium bicarbonate.

As per one embodiment, the present invention contains one or more gastric acids, preferably combination of two gastric acids.

As per one embodiment, gastric acid are selected from sodium bicarbonate, calcium carbonate, potassium carbonate, potassium bicarbonate and sodium carbonate. Most preferably gastric acid are sodium bicarbonate and calcium carbonate.

As per one embodiment the gastric acid can be present in the composition in the range from 1 to 50 gm, preferably 1 to 30 gm, more preferably 1 to 20 gm, most preferably 1 to 10 gm. In a most preferred embodiment the gastric acid is present in the range from 1 to 10 gm.

As per on embodiment, a novel raft forming tablet formulation of dahlia pinnata extract comprising 1-200 gm of methanolic extract of dahlia pinnata, 1-200 gm of combination of two raft forming agents, 1-50 gm of binder, 1-40 gm of sweetener, 1-40 gm of 1-40 gm of lubricant, glidant, 1-50 gm of combination of two gastric acid and vehicle.

As per preferred embodiment, a novel raft forming tablet formulation of dahlia pinnata extract comprising 1-80 gm of methanolic extract of dahlia pinnata, 1-20 gm of combination of sodium alginate and pectin as aft forming agents, 1-5 gm of HPMC K100M as binder, 1-5 gm of Aspartame as sweetener,1-5 gm of Magnesium stearate as lubricant, 1-5 gm of talc as glidant, 1-10 gm of combination of sodium bicarbonate and calcium carbonate as gastric acid and Mannitol as vehicle

As per one embodiment the process of preparation of a novel raft forming tablet formulation of dahlia pinnata extract comprising steps of:
a) Weighing of all ingredients accurately;
b) Mixing of Dahlia pinnata extract, raft forming agents, gastric acid, sweetener and glidant;
c) Dissolving binder in a sufficient quantity of vehicle and adding in the step (a) mixture to prepare a wet mass ;
d) Passing a wet mass from step (c) through 20 mesh sieve to obtain granules;
e) Drying the granules from step (d) in a hot air oven and resifting through 40 mesh sieve;
f) Collecting the granules from step (e) and adding lubricant to it;
g) Compressing the tablet by 12m-mm diameter at punch with the help of a rotary tablet compression machine.
According to one embodiment of the present invention, the novel raft forming tablet formulation of dahlia pinnata extract is useful for the treatment of gastric ulcer.

According to one embodiment of the present invention the novel raft forming tablet formulation of dahlia pinnata extract in which the principal of treatment is formation of raft which is generated by sodium alginate and pectin as raft forming agent in appropriate amount with Dahlia pinnata extracts.

As per one embodiment, the novel raft forming tablet formulation of dahlia pinnata extract is an herbal formulation in which Dahlia pinnata is an herbal alternate of the peptic-ulcer when it merges with such formulation then it will be beneficial for all the patients who are facing such a problem.

The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

EXAMPLES

EXAMPLE 1: A NOVEL RAFT FORMING TABLET FORMULATION OF DAHLIA PINNATA EXTRACT

Sr.
No. Ingredients Quantity taken
1. Methanolic extracts of Dahlia pinnata plant 40 gm
2. Sodium alginate 17 gm
3. Pectin 8.5 gm
4. Sodium bicarbonate 2.8 gm
5. Calcium carbonate 8.5 gm
6. Mannitol 8 gm
7. HPMC K100M 1.6 gm
8. Aspartame 1.1 gm
9. Talc 1 gm
10. Magnesium stearate 0.5 gm
Table: 1 Formulation of dahlia pinnata extract

Procedure:
a) all ingredients were weighed accurately;
b) Dahlia pinnata extract, raft forming agents, gastric acid, sweetener and glidant were mixed;
c) binder was dissolved in a sufficient quantity of vehicle and added in the step (a) mixture to prepare a wet mass ;
d) a wet mass from step (c) was passed through 20 mesh sieve to obtain granules;
e) the granules from step (d) were dried in a hot air oven and resifted through 40 mesh sieve;
f) the granules were collected from step (e) and lubricant was added to it;
g) the tablet was compressed by 12 m-mm diameter at punch with the help of a rotary tablet compression machine.

EXAMPLE 2: EVALUATION PARAMETERS OF RAFT FORMING TABLET

Tablets prepared by wet granulation are evaluated for Tablet dimensions (diameter and thickness), hardness, friability, weight variation and the result is given in following table.
Sr.no. Parameter Avg. Result
1 Diameter (mm) 12 ± 0.01
2 Thickness (mm) 4 ± 0.03
3 Hardness (kg/cm2) 3 ± 0.20
4 %Friability 0.9846
5 %Weight variation Pass
Table: 2 Results of evaluation parameters

EXAMPLE 3: IN VITRO DRUG RELEASE PROFILE
In vitro drug release study of raft forming tablet formulation of Dahlia pinnata extract (Optimized Formulation) was performed using USP (United States Pharmacopoeia) apparatus II fitted with a paddle (50 RPM) at 37 ± 0.5°C using a simulated gastric fluid (pH 1.2; 900 ml) as a dissolution medium. The tablet was added to the dissolution medium. At pre-determined time intervals, 5 ml samples were withdrawn, filtered through a 0.45-µm membrane filter and analyzed at 378 nm (butein) & 520 nm (inulin) using a double-beam spectrophotometer. Cumulative percentage drug release was calculated using an equation obtained from a calibration curve, which was developed in the range 2-20 µg/ml for 0.1 N HCl.
Result:
It was concluded that tablet can release the drug extracts in sustained manner (99.99%) up to 10 hours. Butein was detected at 378 nm and inulin was detected at 520nm in the UV-visible spectrophotometer. The results are shown below:
Time (Hours) % CDR
1 12.36
2 19.14
3 29.13
4 38.47
5 55.12
6 64.32
7 73.41
8 83.14
9 91.14
10 99.98
Table 3: Drug release at 378 nm
Time (Hours) % CDR
1 23.69
2 31.32
3 38.95
4 46.58
5 61.84
6 68.12
7 77.21
8 84.73
9 92.36
10 99.99
Table: 3 Drug release at 520 nm
The result of in-vitro drug release study proves that the raft forming tablet of Dahlia pinnata giving sustained release of drug upto 10 hours (99.99%) and which also proves that all the ingredients works in synergy and formation of raft which is generated by sodium alginate and pectin as raft forming agent in appropriate amount with Dahlia pinnata extract shows sustained effect in the treatment anti-ulcer and present invention offers a good herbal formulation with anti-ulcer potential.
,CLAIMS:CLAIMS
We Claim,
1. A novel raft forming tablet formulation of dahlia pinnata extract comprising 1-200 gm of methanolic extract of dahlia pinnata, 1-200 gm of combination of two raft forming agents, 1-50 gm of binder, 1-40 gm of sweetener, 1-40 gm of 1-40 gm of lubricant, glidant, 1-50 gm of combination of two gastric acid and vehicle.

2. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said dahlia pinnata extract can be used more preferably used in the range of 1-100 gm and most preferably 1-80 gm.

3. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said raft forming agent agents can be selected from sodium alginate, gelatin, pectin, xanthan gum, cellulose, corn starch, agar-agar, pregelatinized starches, arrow root and potassium alginate or combinations therof.

4. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said binder can be selected from but not limited to group consisting of PVP K30, HPMC E50 LV, HPMC K100M, (Poly ethylene glycol) PEG 6000 and Eudragit RL 100.

5. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said lubricant can be selected from but not limited to group consisting of are microcrystalline cellulose, magnesium stearate, castor oil, olive oil, polytetrafluoroethylene, boron nitride, lanolin and palm oil.

6. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said glidant can be selected from but not limited to group consisting of starch, colloidal silicon dioxide, calcium palmitate and talc.

7. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said sweetener can be selected from Aspartame, sucralose, saccharin, honey, stevia, alitame and cyclamates.

8. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 wherein said gastric acid are selected from sodium bicarbonate, calcium carbonate, potassium carbonate, potassium bicarbonate and sodium carbonate.

9. The novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 comprising;
1-80 gm of methanolic extract of dahlia pinnata,
1-20 gm of combination of sodium alginate and pectin as raft forming agents, 1-5 gm of HPMC K100M as binder,
1-5 gm of Aspartame as sweetener,
1-5 gm of Magnesium stearate as lubricant,
1-5 gm of talc as glidant,
1-10 gm of combination of sodium bicarbonate and calcium carbonate as gastric acid and
Mannitol as vehicle.

10. The process of preparation of a novel raft forming tablet formulation of dahlia pinnata extract as claimed in claim 1 comprising steps of:
a) Weighing of all ingredients accurately;
b) Mixing of Dahlia pinnata extract, raft forming agents, gastric acid, sweetener and glidant;
c) Dissolving binder in a sufficient quantity of vehicle and adding in the step (a) mixture to prepare a wet mass;
d) Passing a wet mass from step (c) through 20 mesh sieve to obtain granules;
e) Drying the granules from step (d) in a hot air oven and resifting through 40 mesh sieve;
f) Collecting the granules from step (e) and adding lubricant to it;
g) Compressing the tablet by 12m-mm diameter at punch with the help of a rotary tablet compression machine.

Dated this 30th March, 2023