DESC:FORM 2

THE PATENTS ACT 1970
(SECTION 39 OF 1970)

&
THE PATENT RULES, 2003

COMPLETE SPECIFICATION
(SECTION 10)

MIGRAINE RELIEVING TOPICAL PATCH AND ITS PROCESS OF PREPARATION

We, AZISTA INDUSTRIES PVT LTD
a company incorporated under the companies act, 1956 having address at
Sy. No. 80-84, 4th Floor, C Wing, Melange Towers, Patrika Nagar, Madhapur, Hyderabad, Telangana- 500 081, 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 composition of hydrogel topical patch comprising an essential oil, one or more flavouring agents as active ingredients and pharmaceutically acceptable carriers.

The present invention also relates to a composition of hydrogel topical patch comprising peppermint oil as essential oil, orange flavour as flavouring agent and pharmaceutically acceptable carriers for relieving migraine headache.

The present invention also relates to an efficient process for the preparation of hydrogel topical patch comprising steps of dissolving, mixing, coating, drying, laminating, cutting, pouching and labelling.

BACKGROUND OF THE INVENTION
The exact reason for occurrence of migraine headache is unknown. It is suspected that they result from abnormal activity in the brain. This can affect the way nerves communicate as well as the chemicals and blood vessels in the brain. Genetics may make someone more sensitive to the triggers that can cause migraines. However, the following factors may trigger migraines including hormonal changes, emotional triggers (stress, depression, anxiety, excitement and shock), physical causes (tiredness and insufficient sleep), low blood sugar, jet lag, diet, medications (some sleeping pills, hormone replacement therapy (HRT) medications).

Migraines are severe, recurring, and painful headaches. They can be preceded or accompanied by sensory warning signs and other symptoms. The extreme pain that migraines cause can last for hours or even days. According to the American Migraine Association, they affect 36 million Americans, or approximately 12 percent of the population. Migraines can follow an aura of sensory disturbances followed by a severe headache that often appears on one side of the head. They tend to affect people aged 15 to 55 years.
Peppermint oil has been used as a natural remedy and has variety of medicinal properties including headaches, nausea, gas, indigestion, cold symptoms, skin irritations, anxiety, diarrhea, menstrual cramps, muscle and nerve pain as well as stomach and bowel conditions.

Peppermint oil has analgesic, spasmolytic, anti-inflammatory, antiemetic, antioxidant, antimicrobial and cooling properties.

Peppermint oil proved to be a well-tolerated and cost-effective alternative to usual migraine headache therapies. There were also no adverse side effects reported after peppermint treatment.

Tension associated headaches are often not as debilitating or as painful as the migraine headache. Migraines are often related to poor blood flow and peppermint essential oil can be effective in treating the pain associated with migraine headaches.

A study was conducted and published in the Phytomedicine, 1995, 2(2), 93-102. Thirty-two healthy participants were evaluated, and essential oil treatment was investigated by comparing the baseline and treatment measurements. One effective treatment was a combination of peppermint oil, eucalyptus oil and ethanol.

After topical application, peppermint oil penetrate the skin and relax blood vessels (vasodilation) to stimulate blood flow along with long lasting cooling effect along with relief from migraine headache. In addition, orange flavor can provide additive effect in combination with peppermint oil in relieving migraine headache.

Lancet, May 5, 1979, 1(8123), 966-9 discloses 65% of patients reacted to oranges shown reduced migraines in 100% of patients and completely eliminated migraines in 85 percent of patients.

Journal of Pharmacy and Pharmacology, 1994, 46, 618-630 discloses peppermint oil made from Mentha piperita contains up to 50% menthol. Menthol has the characteristic peppermint odour and exerts a cooling sensation when applied to skin and mucosal surface.

Phytomedicine, 1995, 2 (2), 93-102 discloses local application of peppermint oil which generates a long-lasting cooling effect on the skin, caused by a steric alteration of the calcium channels of the cold-receptors. It also discloses essential oils such as peppermint oil and eucalyptus oil have been put to therapeutic use for the treatment of tension-type headache.

Neurologist, 1996, 67 (8), 672-681 discloses 10% peppermint oil in ethanol solution efficiently alleviates tension-type headache. 41 participants suffering from headaches reported pain relief after peppermint oil was applied topically to the forehead between 15 and 30 minutes after a headache began. Peppermint oil thus proves to be a well-tolerated and cost-effective alternative to usual therapies.

CN 104887750 discloses use of peppermint oil for treating migraine.

US 7,235,257 disclose peppermint oil as an essential oil along with 1-menthol and used for alleviating migraine by dermal administration.

US 8,105,624 disclose topical patch preparation comprising cross-linked adhesive gel composition comprising cross-linked polymer gel, water, water retaining agent, crosslinking agent, inorganic substance, preservative, oil, chelating agent, pH regulator. It also discloses active ingredients of the topical patch preparations are menthol, camphor and mint oil as a cooling effect counterirritant.

US 8,758,312 disclose patch preparation that has extremely low moisture permeability, has a sufficient ODT effect, excellent in drug releasability and in anchoring property of its drug-containing pressure-sensitive adhesive layer, and has a preferred patch feeling. It also discloses peppermint oil as a cooling agent.

US 2015/0110903 disclose peppermint oil as herbal therapeutic agent and it is used for treating headaches.

Journal of Anesthesiology and Pain, 2016, 7(2), 1-12 discloses peppermint long history of use in some disorders, including headache. It also discloses that peppermint extract (menthol) could significantly reduce the intensity, duration and frequency of migraine attacks in combination with prophylactic pharmacologic therapy.

WO 2016/141756 discloses headache relieving patch comprising peppermint essential oil with other ingredients. It also discloses peppermint essential oil has the effect of refreshing, relieving headaches and relieving tension.

Of late various formulations are available to treat migraine headache using peppermint oil, including soft gels, chewables (sublingual tablets that dissolve under the tongue), liquid oil, flavored syrups, candy, gum, tea, soap, shampoo, skin cream, foot spray, inhalation beads and air freshener.

All the prior art references shows the use of peppermint oil for treating migraine and there are various dosage forms of peppermint oil available in market for treating migraine. However, the inventors of present invention provide composition of topical hydrogel patch comprising peppermint oil, orange flavour as active ingredients and pharmaceutically acceptable carriers. The inventors of present invention also provide an efficient process for the preparation of hydrogel topical patch comprising steps of dissolving, mixing, coating, drying, laminating, cutting, pouching and labelling.

OBJECTIVE OF INVENTION
The main objective of the present invention is to provide a composition of hydrogel topical patch comprising an essential oil, one or more flavouring agents as active ingredients and pharmaceutically acceptable carriers.

Another objective of the present invention is to provide hydrogel topical patch composition comprising peppermint oil, orange flavour as active ingredients as orange flavour provides additive effect in combination with peppermint oil in relieving migraine headache.

Another objective of the present invention is to provide a composition of hydrogel topical patch comprising peppermint oil as essential oil, orange flavour as flavouring agent, gel forming material, cross-linking materials, moisturizers, gelation rate modifying materials, surfactants, extender materials, preservatives, flavouring agent and solvent as pharmaceutically acceptable carriers.

Still another objective of the present invention is to provide process for the preparation of hydrogel topical patch comprising steps of dissolving, mixing, coating, drying, laminating, cutting, pouching and labelling.

Still another objective of the present invention is to provide process for the preparation of hydrogel topical patch comprising steps of dissolving gel forming material in water, adding active ingredient and other pharmaceutically acceptable carriers by stirring to form hydrous base gel, coating, drying, laminating and cutting into desired size.

Still another objective of the present invention is to provide an improved manufacturing process for preparation of hydrogel topical patch by chemical cross-linking technique at room temperature, which reduces the loss of water and essential oil during manufacturing process.
In yet another objective of the present invention is to provide relief from migraine headache by topical application of peppermint oil hydrogel patch.

SUMMARY OF INVENTION
Accordingly, the present invention provides a composition of hydrogel topical patch useful in facilitating and relieving migraine headache.

In one embodiment, the present invention provides hydrogel topical patch composition comprising essential oil, one or more flavouring agents as active ingredients and pharmaceutically acceptable carriers.

In another embodiment, the present invention provides hydrogel topical patch composition comprising one or more active ingredients, gel forming material, cross-linking materials, moisturizers, gelation rate modifying materials, surfactants, extender materials, preservatives and solvent as pharmaceutically acceptable carriers.

In another embodiment, the present invention provides hydrogel topical patch composition comprising peppermint oil, orange flavour as active ingredients and pharmaceutically acceptable carriers.

In another embodiment, the present invention provides hydrogel topical patch composition comprising peppermint oil, orange flavour as active ingredients, polyacrylic acid, sodium polyacrylic acid (synthetic acrylate derivatives) and gelatin ( natural collagen derivative) as gel forming material, glycerin and propylene glycol as moisturizers, dihydroxyaluminum aminoacetate as cross-linking agent, sorbitan monooleate as surfactant, methylparaben and propylparaben as preservatives, tartaric acid and disodium EDTA as gelation rate modifiers, aluminium silicate and titanium dioxide as extenders, water as solvent.

In another embodiment, the present invention provides composition of hydrogel topical patch comprising:
(a) 1% to 5% (w/w) of one or more active ingredients,
(b) 10% to 25% (w/w) of gel forming materials,
(c) 2% to 16% (w/w) of the cross-linking materials,
(d) 25 to 60 % (w/w) of moisturizers,
(e) 0.1 to 0.7 % (w/w) of gelation rate modifying materials,
(f) 0.25 to 1 % (w/w) of surfactant,
(g) 0.25 to 1.5 % (w/w) of extender materials,
(h) 0.002 to 0.2 % (w/w) of preservative materials, and
(i) 25% to 50% of water.

In another embodiment, the present invention provides composition of hydrogel topical patch comprising:
(a) 2% to 6% (w/w) of peppermint oil,
(b) 0.5% to 2% (w/w) of orange flavour,
(c) 10% to 25% (w/w) of the combination of synthetic acrylate derivatives and natural collagen derivative gel forming material,
(d) 2% to 16% (w/w) of the cross-linking materials,
(e) 25 to 60 % (w/w) of moisturizers,
(f) 0.1 to 0.7 % (w/w) of gelation rate modifying materials,
(g) 0.25 to 1 % (w/w) of surfactant,
(h) 0.25 to 1.5 % (w/w) of extender materials,
(i) 0.002 to 0.2 % (w/w) of preservative materials, and
(j) 25% to 50% of water.

In another embodiment, the present invention also provides an improved process for the preparation of hydrogel topical patch involving chemical cross-linking technique to reduce the loss of peppermint oil and water during manufacturing process.
In yet another embodiment, the present invention provides process for preparing hydrogel topical patch, wherein the process comprising steps of:
(a) dissolving synthetic acrylate derivatives gel forming material, gelation rate modifiers, moisturizers in purified water under stirring at 60ºC to get Phase A,
(b) dissolving natural collagen derivative gel forming material in purified water under stirring at 60ºC to get Phase B,
(c) mixing Phase A and Phase B under stirring,
(d) mixing separately one or more active ingredients, surfactant, preservatives under stirring to get Phase C,
(e) adding Phase C to the mixture of Phase A and Phase B under stirring,
(f) mixing extender materials, cross-linking agent to get Phase D,
(g) adding Phase D to the mixture of Phase (A+B+C) under stirring and homogenization,
(h) coating on to the polyester or silicone coated polyethylene release liner and allowing for cross-linking,
(i) laminating the obtained cross-linked hydrogel matrix, and
(j) cutting into desired size to get hydrogel patch, pouching and labelling.

DETAILED DESCRIPTION OF THE INVENTION
The term "comprising", which is synonymous with "including", "containing", or "characterized by" here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.

The present invention provides composition of hydrogel topical gel comprising one or more active ingredients, pharmaceutically acceptable carrier and its process of preparation.

The present invention provides hydrogel topical patch composition comprising peppermint oil, orange flavour as active ingredients and gel forming agents, cross-linking agents, moisturizer or water retaining agents, gelation rate modifier, medicinal dispersant, extender, preservative, solvent as pharmaceutically acceptable carriers.

The term “active ingredients” of the present invention is used to relieve migraine headache. Preferably used active ingredients are peppermint oil and orange flavour.

Peppermint has been used as a natural remedy and herbal treatment for headaches, nausea, gas, irritable bowel syndrome (IBS), and other conditions. Some people use peppermint leaf or peppermint oil as a dietary supplement, and others use peppermint essential oil applied directly to the skin.

Peppermint oil has a tingling or cooling effect on the skin that can cause a slight numbing effect. It is believed that these properties may make peppermint oil helpful for people who suffer from migraine. For some people, applying peppermint oil to the forehead and/or temples can provide some relief from migraine pain.

Sixty-five percent of patients reacted to oranges in a 1979 study that reduced migraines in 100 percent of patients and completely eliminated migraines in 85 percent of patients.

The effective peppermint oil penetrate the skin and relax blood vessels (vasodilation) to stimulate blood flow along with long lasting cooling effect when applied topically. In addition, orange flavor can provide additive effect in combination with peppermint oil in relieving migraine headache.

The concentration of essential oil used in the hydrogel topical patch is in the range of 2% to 6% (w/w).
The concentration of flavouring agent used in the hydrogel topical patch is in the range of 0.5% to 2% (w/w).

The concentration of the essential oil and flavouring agent used in the hydrogel topical patch is in the range of 1% to 5% (w/w), most preferably in the range of 1% to 4%.

The term “gel forming agents” of the present invention includes combination of synthetic and natural gel forming material and includes at least two polymers selected group polyacrylic acid, sodium polyacrylate and partially neutralized polyacrylate, cellulose derivatives [carboxymethyl cellulose (CMC), carboxymethyl cellulose sodium (CMCNa), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and gelatin. Preferably, gel forming agents are polyacrylic acid, sodium polyacrylate and gelatin.

The concentration of gel forming materials used in hydrogel topical patch is in the range of 10% to 25% (w/w), most preferably in the range of 10% to 20% (w/w).

Cross-linking agents used alone or in combination in the compositions of the present invention include, but are not limited to dried aluminum hydroxy gel, dihydroxyaluminum acetate, dihydroxyaluminium aminoacetate, magnesium aluminometasilicate, aluminum hydroxide, magnesium metasilicate aluminate, synthetic aluminum silicate, calcium hydroxide, aluminum ammonium sulfate, and calcium chloride and aluminium glycinate. Preferably, the cross-linking agent is dihydroxyaluminium aminoacetate.

The concentration of cross-linking agents or materials used in hydrogel topical patch is in the range of 2% to 16% (w/w), most preferably in the range of 2% to 14% (w/w).

Moisturizers includes but not limited to aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, aluminum hydroxide gel, cocoa butter, propylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, hard fat, kaolin, mineral oil, petrolatum, topical starch, white petroleum, cod liver oil, shark liver oil, zinc oxide, polyethylene glycol, sorbitol, maltitol, 1,3-butylene glycol or any combination thereof. Preferably, the moisturizers are glycerin and propylene glycol.

The concentration moisturizers used in the is in the hydrogel topical patch range of 25% to 60% (w/w), most preferably in the range of 30% to 50% (w/w).

The term “gelation rate modifiers” of the present invention includes chelating agent and/or organic acids.

Chelating agent includes but not limited to sodium edetate (EDTA), glucono delta lactone and sodium polyphosphates such as sodium metaphosphate. Preferably, the chelating agent is disodium EDTA.

Organic acids includes but not limited to aliphatic (mono, di, tri) carboxylic acids (e.g., acetic acid, propionic acid, iso-butyric acid, caproic acid, lactic acid, maleic acid, pyruvic acid, oxalic acid, succinic acid, tartaric acid and the like), aromatic carboxylic acids (e.g., phthalic acid, salicylic acid, benzoic acid, acetyl salicylic acid and the like), alkyl sulfonic acids (e.g., ethane sulfonic acid, propyl sulfonic acid, butane sulfonic acid, polyoxyethylene alkyl ether sulfonic acid and the like), alkyl sulfonic acid derivatives (e.g., N-2-hydroxyethyl piperidine-N'-2-ethane sulfonic acid (it is abbreviated as `HEPES` hereinafter), cholic acid derivatives (e.g., dehydrocholic acid and the like), citric acid, malic acid. Preferably, the organic acid is tartaric acid.

The concentration of gelation rate modifying materials used in the hydrogel topical patch in the range of 0.1% to 0.7% (w/w), most preferably in the range of 0.1% to 0.5% (w/w).
Surfactants for emulsifying the oils in aqueous phases include but not limited to polyoxyethylene sorbitan monooleate, poly oxyethylene sorbitan monostearate, sorbitan monooleate, sorbitan monopalmitate. Preferably, the surfactant is sorbitan monooleate.

The concentration of surfactants used in the hydrogel topical patch is in the range of 0.25% to 1 % (w/w), most preferably in the range of 0.5% to 1% (w/w).

Extender materials include but not limited to kaolin, bentonite, aluminium silicate, titanium dioxide. Preferably, the extender materials are aluminium silicate and titanium dioxide.

The concentration of extender materials used in the hydrogel topical patch is in the range of 0.25% to 1% (w/w), most preferably in the range of 0.25% to 1% (w/w).

Preservatives include but not limited to methyl paraben, propyl paraben, benzoyl alcohol, phenoxy ethanol. Preferably, the preservatives are methyl paraben and propyl paraben.

The concentration of preservatives used in the hydrogel topical patch is in the range of 0.002% to 0.2% (w/w), most preferably in the range of 0.001% to 0.105% (w/w).

Solvent include but not limited to water, ethanol, isopropyl alcohol, heptane, ethyl acetate. Preferably, the solvent is water.

The hydrogel topical patch preparation of present invention has been prepared by chemical cross-linking technique. The advantage of this technique is simple and easy to manufacture at room temperature and reduces the loss of peppermint oil, orange flavour and water evaporation during manufacture.
The hydrogel patch preparation of present invention has been prepared by coating the hydrous gel preparation on polyester or silicone coated polyethylene release liner and cross-linked hydrogel matrix layer is laminated using nonwoven or woven fabric backing material.

The hydrous gel preparation comprising the Polyacrylic acid and sodium polyacrylate but hardness and cohesive property of gel matrix is not achieved alone with polyacrylic acids. These physical & mechanical properties of gel matrix are achieved only with the combination of polyacrylic acids and gelatin to get the desired tackiness & flexibility to gel matrix.

The content of polyacrylic acid, sodium polyacrylate and gelatin should contain 10% to 20% by mass with respect to total mass of adhesive layer. If the content falls within this range, the cohesive property and tack of adhesive layer can be maintained. Accordingly, favorable application properties can be obtained.

For the hydrous gel matrix preparation of present invention, it is preferred that the moisturizers and water used alone or in combination to provide cooling and soothing effect. The concentration of moisturizer should be in the range of 25-50% and water concentration should be in the range of 25-50% by mass with respect to total mass of gel matrix.

For the hydrous gel matrix preparation of present invention, it is preferred that the cross-linker dihydroxyaluminum aminoacetate play a key role in cross-linking and to maintain gel matrix integrity after coating at room temperature. The physical and mechanical properties of gel matrix are achieved only with the optimized concentration of cross-linker to get the desired tackiness & flexibility to gel matrix. The concentration of cross-linker should be in the range of 4-14% by mass with respect to total mass of gel matrix.

For the hydrous gel matrix preparation of present invention, it is preferred that the remaining excipients including surfactants, preservatives, extender and dispersant should be in the range of 1-5%. All these excipients should be used in minor quantity to provide its respective action.

Various properties associated with each component of the hydrogel patch compositions may affect the properties of the final product. Properties associated with the selection of raw materials, molecular weight, concentration, bloom strength and viscosity may influence the intact hydrogel formation, adhesion, cooling effect and therapeutic effect.

The invention disclosed herein is process for the preparation of hydrogel topical patch useful in facilitating to relieve migraine.

Manufacturing process for hydrogel topical patch.

1. Preparation of polyacrylic acid solution phase (Phase A)
The polyacrylic acid solution phase is prepared by addition of polyacrylic acid, polyacrylic acid sodium, tartaric acid, disodium EDTA, glycerine, propylene glycol to water under stirring preferably at 60oC temperature. Later, mixture is homogenized to obtain homogenous solution. Preferably, the concentration of polyacrylic acid should be in the range of 1-5% (w/w), preferably, polyacrylic acid sodium should be in the range of 4-8% (w/w), preferably, tartaric acid should be in the range of 0.1-0.5% (w/w), preferably, disodium EDTA should be in the range of 0.1-0.5% (w/w), preferably, glycerine should be in the range of 25-40% (w/w), preferably, propylene glycol should be in the range of 1-3% (w/w), preferably, the purified water should be around 70% (w/w) of batch size.

2. Preparation of gelatine solution (Phase B)
The gelatin is used to prepare is gelatin solution and is prepared by addition of gelatin to hot water under stirring, preferably at 60ºC temperature. Preferably, the concentration of gelatin should be in the range of 4-8% (w/w). Preferably, the purified water should be around 30% (w/w) of batch size.

3. Preparation of peppermint oil phase (Phase C)
Mix peppermint oil, orange flavour, sorbitan monooleate, methyl paraben and propyl paraben under stirring at room temperature. Preferably, the concentration of peppermint oil should be in the range of 2-6% (w/w), preferably, the concentration of orange flavour should be in the range of 0.5-2% (w/w), preferably, the concentration of sorbitan monooleate should be in the range of 0.25-1% (w/w), preferably, the concentration of methyl paraben should be in the range of 0.005-0.2% (w/w), preferably, the concentration of propyl paraben should be in the range of 0.002-0.1% (w/w).

4. Preparation of cross-linker phase (Phase D)
Mix all the powders including dihydroxyaluminium aminoacetate (DHAAA), aluminium silicate and titanium dioxide. Preferably, the concentration of DHAAA should be in the range of 4-8% (w/w), preferably, the concentration of aluminium silicate should be in the range of 0.25-1% (w/w), preferably, the concentration of titanium dioxide should be in the range of 0.25-1% (w/w).

5. Preparation of hydrous gel base
Mix phase A and phase B under stirring to obtain homogenous mixture. To the A+B mixture add phase C under stirring and finally add phase D to the A+B+C mixture under stirring and homogenization to obtain homogenous mixture blend for coating.

6. Coating
The hydrous gel matrix was uniformly coated with desired thickness on to the polyester or silicone coated polyethylene release liner and was allowed to cross-link at room temperature.
7. Lamination and cutting and packaging
Then this cross-linked hydrogel matrix was laminated using Nonwoven fabric.

8. Cutting and packaging
Then the resulting product cut into a desired size to produce hydrogel patch and finally packed in triple laminated aluminum pouch.

Formulations were developed using different concentrations of polyacrylic acid, gelatin and DHAAA. The formulations prepared with different variations were evaluated for their description, adhesion (tack), peel test, assay.

The following examples describes the nature of the invention and are given only for the purpose of illustrating the present invention in more detail and are not limitative and relate to solutions, which have been particularly effective on bench scale and prepared by the process of the present invention.

Example 1
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 6
3. Gelatin 5
4. Glycerine 30
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 3
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 2
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 7.5
3. Gelatin 5
4. Glycerine 30
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 8
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 3
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 5
2. Sodium polyacrylic acid 10
3. Gelatin 5
4. Glycerine 30
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 5
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 4
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 7.5
3. Gelatin 5
4. Glycerine 35
5. Propylene glycol 5
6. Dihydroxyaluminum aminoacetate 8
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 5
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 7.5
3. Gelatin 5
4. Glycerine 45
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 6
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 6
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 7.5
3. Gelatin 5
4. Glycerine 45
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 8
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 7
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 7.5
3. Gelatin 5
4. Glycerine 30
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 10
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Example 8
S.No. Ingredient Concentration (% w/w)
1. Polyacrylic acid 2.5
2. Sodium polyacrylic acid 7.5
3. Gelatin 5
4. Glycerine 30
5. Propylene glycol 2
6. Dihydroxyaluminum aminoacetate 12
7. Peppermint oil 3
8. Orange flavour 1
9. Sorbitan monooleate 0.5
10. Methylparaben 0.1
11. Propylparaben 0.005
12. Tartaric acid 0.25
13. Di sodium EDTA 0.25
14. Aluminium silicate 0.5
15. Titanium dioxide 0.5
16. Purified water q.s to 100

Manufacturing process:
Required quantity of poly acrylic acid and poly acrylic acid sodium salt , tartaric acid, disodium EDTA, glycerin and propylene glycol were added to 60 % of batch quantity of purified water at 60ºC under stirring and homogenization to obtain homogenous solution (Phase A).

Required quantity of gelatin was added to remaining batch quantity of purified water under stirring at 60ºC temperature to obtain solution (Phase B).
Required quantity of peppermint oil, orange flavor, sorbitan monooleate, methylparaben and propylparaben mix under stirring (Phase C).

Required quantity of all powders aluminum Silicate, titanium dioxide and dihydroxyaluminum aminoacetate mix together (Phase D).

Mix phase A and phase B under stirring to obtain homogenous mixture. To the A+B mixture add phase C under stirring and finally add phase D to the A+B+C mixture under stirring and homogenization to obtain homogenous mixture blend for coating.

Table 1. Specifications for migraine pain relieving hydrogel patch:

S.No. Test Specification
1 Description Clear transparent circular patch laminated with white color non-woven fabric packed in zip-lock triple laminated aluminum pouch
2 Size 9 cm2
3 Avg. weight 0.575±5% (0.546 g -0.604g)
4 Uniformity of dosage units (by content uniformity) The acceptance value is L1= 15
5 Preservative content Between 80-110% of label claim
6 Assay (Menthol content) Between 80-110% of label claim

The migraine pain relieving hydrogel patch prepared as per Example 1 of the present invention is evaluated for the above characters at 25°C/60% RH stability conditions and the data is given below table;

Table 2
Stability Condition: 25°C/60% RH
Tests Specification Initial 3 Month
Description White coloured circular patch laminated with white color non-woven fabric packed in zip-lock triple laminated aluminum pouch White coloured circular patch laminated with white color non-woven fabric packed in zip-lock triple laminated aluminum pouch White coloured circular patch laminated with white color non-woven fabric packed in zip-lock triple laminated aluminum pouch
Size 9 cm2 9 cm2 9 cm2
Avg. weight 0.575±5% (0.546 g -0.604g) 0.578 g 0.562 g
Preservative content Between 80-110% of label claim 100.5 % 100.1%
Assay (Menthol content)
Between 80-110% of label claim 100.8% 100.2%

,CLAIMS:We Claim:
1. Hydrogel topical patch composition comprising essential oil, one or more flavouring agents as active ingredients and pharmaceutically acceptable carriers.
2. Hydrogel topical patch composition as claimed in claim 1, wherein the essential oil is peppermint oil.
3. Hydrogel topical patch composition as claimed in claim 1, the essential oil is in the range of 2% to 6% (w/w).
4. Hydrogel topical patch composition as claimed in claim 1, wherein the flavouring agent is orange flavour.
5. Hydrogel topical patch composition as claimed in claim 1, the flavouring agent is in the range of 0.5% to 2% (w/w).
6. Hydrogel topical patch composition as claimed in claim 1, wherein pharmaceutically acceptable carriers are selected from gel forming material, cross-linking materials, moisturizers, gelation rate modifying materials, surfactants, extender materials, preservatives, flavouring agent and solvent.
7. Hydrogel topical patch composition comprising:
(a) peppermint oil,
(b) orange flavour,
(c) gel forming materials,
(d) cross-linking material,
(e) moisturizers,
(f) gelation rate modifying materials,
(g) surfactant,
(h) extender materials,
(i) preservative materials, and
(j) water.
8. Hydrogel topical patch composition as claimed in claim 7, wherein gel forming materials is a combination of synthetic acrylate derivatives and natural collagen derivative.
9. Hydrogel topical patch composition as claimed in claim 7, wherein gel forming materials includes at least two polymers selected from group polyacrylic acid, sodium polyacrylic acid and partially neutralized polyacrylate, cellulose derivatives [carboxymethyl cellulose (CMC), carboxymethyl cellulose sodium (CMCNa), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and gelatin.
10. Hydrogel topical patch composition as claimed in claim 7, wherein the gel forming materials is in the range of 10% to 25% (w/w), specifically in the range of 10% to 20% (w/w).
11. Hydrogel topical patch composition as claimed in claim 7, wherein cross-linking material is selected from dried aluminum hydroxy gel, dihydroxyaluminum acetate, dihydroxyaluminium aminoacetate, magnesium aluminometasilicate, aluminum hydroxide, magnesium metasilicate aluminate, synthetic aluminum silicate, calcium hydroxide, aluminum ammonium sulfate, and calcium chloride and aluminium glycinate.
12. Hydrogel topical patch composition as claimed in claim 7, wherein cross-linking material is in the range of 2% to 16% (w/w), specifically in the range of 2% to 14% (w/w).
13. Hydrogel topical patch composition as claimed in claim 7, wherein moisturizers are selected from aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, aluminum hydroxide gel, cocoa butter, propylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, hard fat, kaolin, mineral oil, petrolatum, topical starch, white petroleum, cod liver oil, shark liver oil, zinc oxide, polyethylene glycol, sorbitol, maltitol, 1,3-butylene glycol or any combination thereof.
14. Hydrogel topical patch composition as claimed in claim 7, wherein moisturizers is in the range of 25% to 60% (w/w), specifically in the range of 30% to 50% (w/w).
15. Hydrogel topical patch composition as claimed in claim 7, wherein gelation rate modifying materials includes chelating agent selected from sodium edetate (EDTA), glucono delta lactone and sodium polyphosphates such as sodium metaphosphate and/or organic acids selected from aliphatic (mono, di, tri) carboxylic acids (e.g., acetic acid, propionic acid, iso-butyric acid, caproic acid, lactic acid, maleic acid, pyruvic acid, oxalic acid, succinic acid, tartaric acid and the like), aromatic carboxylic acids (e.g., phthalic acid, salicylic acid, benzoic acid, acetyl salicylic acid and the like), alkyl sulfonic acids (e.g., ethane sulfonic acid, propyl sulfonic acid, butane sulfonic acid, polyoxyethylene alkyl ether sulfonic acid and the like), alkyl sulfonic acid derivatives (e.g., N-2-hydroxyethyl piperidine-N'-2-ethane sulfonic acid (it is abbreviated as `HEPES` hereinafter), cholic acid derivatives (e.g., dehydrocholic acid and the like), citric acid, malic acid.
16. Hydrogel topical patch composition as claimed in claim 7, wherein gelation rate modifying materials are in the range of 0.1% to 0.7% (w/w), specifically in the range of 0.1% to 0.5% (w/w).
17. Hydrogel topical patch composition as claimed in claim 7, wherein surfactant is selected from polyoxyethylene sorbitan monooleate, poly oxyethylene sorbitan monostearate, sorbitan monooleate and sorbitan monopalmitate.
18. Hydrogel topical patch composition as claimed in claim 7, wherein surfactant is in the range of 0.25% to 1 % (w/w), specifically in the range of 0.5% to 1% (w/w).
19. Hydrogel topical patch composition as claimed in claim 7, wherein extender materials are selected from kaolin, bentonite, aluminium silicate and titanium dioxide.
20. Hydrogel topical patch composition as claimed in claim 7, wherein extender materials are in the range of 0.25% to 1% (w/w), specifically in the range of 0.25% to 1% (w/w).
21. Hydrogel topical patch composition as claimed in claim 7, wherein preservative materials are selected from methyl paraben, propyl paraben, benzoyl alcohol and phenoxy ethanol.
22. Hydrogel topical patch composition as claimed in claim 7, wherein preservative materials are in the range of 0.002% to 0.2% (w/w), specifically in the range of 0.001% to 0.105% (w/w).
23. Process for preparing hydrogel topical patch as claimed in claim 1, wherein the process comprising steps of:
(a) dissolving synthetic acrylate derivatives gel forming material, gelation rate modifiers, moisturizers in purified water under stirring at 60ºC to get Phase A,
(b) dissolving natural collagen derivative gel forming material in purified water under stirring at 60ºC to get Phase B,
(c) mixing Phase A and Phase B under stirring,
(d) mixing separately one or more active ingredients, surfactant, preservatives under stirring to get Phase C,
(e) adding Phase C to the mixture of Phase A and Phase B under stirring,
(f) mixing extender materials, cross-linking agent to get Phase D,
(g) adding Phase D to the mixture of Phase (A+B+C) under stirring and homogenization,
(h) coating on to the polyester or silicone coated polyethylene release liner and allowing for cross-linking,
(i) laminating the obtained cross-linked hydrogel matrix, and
(j) cutting into desired size to get hydrogel patch, pouching and labelling.

Dated this Thirteenth (13th) day of August, 2019.

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Dr. S. Padmaja
Agent for the Applicant
IN/PA/883