FIELD OF THE INVENTION
The present invention relates to a pharmaceutical formulation for the
management of symptoms of Osteoarthritis. More preferably, the
formulation is used in the management of pain and stiffness due to joint
degeneration. The present formulation can be formulated in various
dosage forms such as tablets, capsules, sachets etc for oral
administration and^ cream, gels, lotion, ointment, liniment etc for topical
administration.
PRIOR ART OF THE INVENTION
US 20050232980 disclose method and composition for a formulation applied to the skin in a transdermal delivery system to address discomfort from various musculoskeletal conditions. The formulation comprises 0.01% to 20% by weight of glucosamine, 0.01% to 20% by weight of chondroitin sulfate, 0.01% to 10% by weight of camphor, 0.01% to 10% by weight of menthol, 0.01% to 20% by weight of an anti¬inflammatory agent, and a transdermal component.

US 20160317480 disclose a Composition and Method of Pain Relief, Reduction of Inflammation, Maintenance of Joints, and Soothing Muscle Soreness which alleviates pain and inflammation from muscle strain, spasms, arthritis, and bursitis. The composition and method for alleviation of pain and inflammation generally includes a combination of Lidocaine HCL, camphor, menthol, Bisabolol, glucosamine hydrochloride (glucosamine HCI), chondroitin, and MSM, along with a number of other ingredients.
US 20140163105 relate to a composition for pain relief including synergistically effective amounts of an amino benzoate local anesthetic, methylsulfonylmethane (MSM), and ethoxydiglycol. A method of treating pain, by applying the composition to skin in an area of pain, and blocking nerve signals. A method of improving range of motion in an individual, by applying the composition to skin, relieving pain, and allowing the individual to have an improved range of motion at an area of pain.

US 20070264370 relates to composition comprising dry powder of decursjnol, decursin, and their related derivates isolated from the roots of Angelica gigas Nakai (Korean Angelica) plant and at least one of joint improvement agents such as glucosamine, chondroitin, or methylsulfonylmethane (MSM).
US 5719197 relates to the compositions for topical application comprising a therapeutically effective amount of a pharmaceutical agent(s), a pharmaceutical^ acceptable bioadhesive carrier, a solvent for the pharmaceutical agent(s) in the carrier and a clay, and methods of administering the pharmaceutical agents to a mammal are disclosed.
Thus there is a need of the formulation which comprises important active ingredients used in the treatment of joint disorders. The present invention comprises of Glucosamine, Camphor, Chondritin, Diacerein, Menthol and Capsaicin along with pharmaceutical excipients. The pharmaceutical excipients used will depend upon the type of dosage form formulated according to the present invention. The dosage form,

may be, but not limited to, tablets, capsules, gels, lotions, creams, and ointments.
OBJECTIVES OF THE INVENTION
The object of the present invention is to provide a formulation used to treat the joint related disorder.
Yet another object of the present invention is to provide a stable formulation to treat joint pain and inflammation.
Yet another object of the present invention is to provide a method of the formulation for a stable formulation comprising various ingredients used to manage the symptoms of joint disorders such as osteoarthritis.
Yet another object of the present invention is to provide various dosage forms comprising Glucosamine, camphor, chondroitin, diacerein, menthol and capsaicin.
Another object of the present invention is to formulate various dosage forms such as tablets, capsules, gels, lotions, creams, and ointments.

DETAILED DESCRIPTION OF THE INVENTION
Osteoarthritis (also known as OA) is a common joint disease that most
often affects middle-age to elderly people. It is commonly referred to as
"wear and tear" of the joints. OA is a disease of the entire joint,
involving the cartilage, joint lining, ligaments, and bone. It is
characterized by breakdown of the cartilage (the tissue that cushions
the ends of the bones between joints), bony changes of the joints,
, deterioration of tendons and ligaments, and various degrees of
inflammation of the joint lining (called the synovium.
The present invention discloses the formulation used in the
management of the joint related disorder symptoms. The present
invention comprises Glucosamine, camphor, chondroitin, diacerein,
menthol and capsaicin.
The present invention also discloses the dosage form comprising the active ingredients such as tablets, capsules, gels, lotions, creams, and ointments.

The present invention also discloses in detail, the method of manufacture of the preferred embodiments.
Other elements may be added to the composition, such as fragrance, anti-pruritic (anti-itch) agents, skin emollients (such as Vitamin E, Vitamin D, or aloe barbadensis gel), citric acid to adjust the pH of the compound, propylene glycol with methyl and propyl parabens as preservatives, chelating agent such as edentate disodium to keep the product from separating, triethanolamine hydrochloride to act as a reagent, and other preservatives.
Glucosamine is a naturally occurring chemical found in the human body. It is in the fluid that is around joints. Glucosamine produced in the body provides natural building blocks for growth, repair and maintenance of cartilage. Like chondroitin, glucosamine may lubricate joints, help cartilage retain water and prevent its breakdown.
Glucosamine in the present invention means Glucosamine as well as its pharmaceutically acceptable salts.

Historically, camphor is derived from aromatic wood that was sold in Indonesia since ancient times. In the 9th century, the first formula for the production of camphor was recorded by Alkindus, a well-known chemist. In the 19th century, camphor became quite popular as an ingredient in pain relieving ointments and salves. Camphor exhibits anti-arthritic, anti-rheumatic and antiphlogistic properties. Its topical application not only reduces swelling in certain body parts but also helps in boosting the blood circulation, thereby relieving strain in the joints.
Chondroitin sulfate is a glycosaminoglycan that functions as a component of proteoglycans. Proteoglycans are found throughout the human body, forming the intricate extracellular matrix. Glycosaminoglycans have also interactive-roles in cell-cell recognition and cell growth.. Used with glucosamine, chondroitin sulfate alleviates pain and inflammation from osteoarthritis and reportedly has a beneficial effect on degenerated joints.
Diacerein is newly introduced one of the symptomatic slow acting drug for OA. It is a semi-synthetic anthraquinone derivative extracted from

certain plants. It directly inhibits IL-1 synthesis and release in vitro and down modulates IL-1 induced activities and have been shown to posses disease modifying effect in experimental models of osteoarthritis and in human subjects with finger joint and knee osteoarthritis. IL-1 plays a fundamental role in osteoarthritis pathophysiology and cartilage destruction. IL-1 also promotes expression of inducible nitric oxide synthase, increase release of prostaglandin E2, IL-6, IL-8 in human osteoarthritis chondrocytes, which promote joint degradation. Hence; by inhibiting IL-1 diacerein retards all pathological prepossess initiated in OA. Diacerein also inhibits IL-1 induced expression of cartilage degrading enzymes. It also enhances expression of TGF BETA-1 and TGF BETA 2 thus favoring matrix synthesis and turnover in articular chondrocytes, thereby accounting for disease modifying property of diacerein. It also inhibits superoxide production, chemotaxis and phagocytic activity of neutrophils in addition to effect on macrophage migration and phagocytosis. In contrast to NSAIDS diacerein does not inhibit synthesis of prostaglandins; hence no gastric toxicity has been observed with

diacerein. It is also demonstrated to be involved in prevention of loss of hydroxyproline and proteoglycans in the joint cartilage, an effect not observed with conventional NSAIDS or COX-2 inhibitors. In nature, menthol is an organic compound obtained from peppermint oil with local anesthetic and counter-irritant qualities. The main form occurring in nature is (-) menthol, which has low toxicity.
Menthol is readily absorbed by the skin and is contained in products used for relief of muscle aches, sprains, and similar conditions. When applied to the skin, menthol stimulates the nerves for the perception of cold, while depressing those which perceive pain. The preliminary feeling of coolness is soon followed by a sensation of warmth.
Capsaicin cream is considered an analgesic and has properties that help to ease arthritis pain by desensitizing the surrounding tissue. Topical capsaicin works by warming the area while also depleting or interfering with substance P, a chemical involved in transmitting pain impulses to the brain. This in turn minimizes the amount of pain felt by the user

N,
while at the same time giving the skin and the underlying layers of tissue a feeling that is pleasant and warm.
The present invention relates to the active ingredients comprising Glucosamine or its pharmaceutical^ acceptable salts, Camphor or its pharmaceutical^ acceptable salts, chondroitin or its pharmaceutical^ acceptable salts, Diacerein or its pharmaceutical^ acceptable salts, menthol or its pharmaceutical^ acceptable salts and capsaicin or its pharmaceutical^ acceptable salts.
Glucosamine sulphate concentration used in the present invention ranges from 5% w/w to 15% w/w, preferably 8% w/w to 13% w/w, and more preferably 10% w/w.
The concentration of camphor in the present invention, ranges from 0.5% w/w to 2% w/w, preferably 1% w/w. Chondroitin Sulphate used in the present invention ranges from 0.5% w/w to 2% w/w, preferably 1% w/w. Diacerein used in the present formulation ranges from 0.5% w/w to 2% w/w, preferably 1% w/w. Menthol used in the present invention ranges from 2% w/w to 10% w/w, preferably 5% w/w.

The concentration of capsaicin used in the present invention ranges from 0.025% w/w to 0.075% w/w, preferably 0.05% w/w.
The formulation may also optionally comprise of other ingredients such as comfrey root extract, Cissus quadrangularis, oil of wintergreen, Linseed oil, Vitamin E, Vitamin D and aloe barbadensis.
The present invention can be manufactured, but not limited to, in the following manner:

PROCEDURE:-
A) AQUEOUS PHASE:
• Take 40 Kg of Purified water and add Sodium Meta-bisulphite stir to get dissolve.
• Add Glucosamine sulphate potassium chloride to above solution and stir to get clear solution.
• Now add xanthum Gum to above solution with stirring to obtained gel like mass.
• Now heat the above mass at 40°C-50°C to about 30 minutes to get uniform mass.
B) NONAQUEOUS PHASE:
• Take Glyceryl Monostearate, Stearic acid, and Emulsifying wax in to SS container and heat to about 60°C-70°C to get uniform liquid phase.
• Add methyl paraben stir to get dissolve then add propyl paraben stir to get dissolve.
• Add capsaicin to above oil phase and stir to get dissolve.

• Now cool the above solution at 40°G with constant stirring.
• Now add camphor and menthol with continuous stirring to get uniform.
• Transfer the non aqueous phase in to the aqueous phase with constant stirring at 40°C.
C) DIACEREIN SOLUTION PREPERATION:
• Take Propylene Glycol and add Diacerein with constant stirring to get slurry (yellow color slurry) for 30 minutes.
• Now transfer above in above bulk.
• Make up the final weight with purified water up to 100 Kg.

We Claim:
1) A topical pharmaceutical formulation comprising Glucosamine,
camphor, menthol, diacerein and capsaicin along with the
pharniaceutically acceptable excipients for the management of
osteoarthritis.
2) The topical formulation as claimed in claim 1 further comprises the chondroitin, comfrey root extract, Cissus quadrangularis, oil of wintergreen, Linseed oil, Vitamin E, Vitamin D and aloe barbadensis.
3) The pharmaceutical^ acceptable excipients as claimed in claim 1 can be thickening agents, emulsifying agents, humectants, solvent, preservatives, antioxidants, and ointment base.
4) Glucosamine as claimed in claim 1 is in the range 5% to 15%,
preferably 10%.
5) Camphor as claimed in claim 1 is in the range 0.5% to 2%, preferably 1%.
6) Menthol as claimed in claim 1 is in the range 2% to 10%, preferably 5%.
7) Capsaicin as claimed in claim 1 is in the range 0.025% to 0.075%, preferably 0.05%.

8) Chondroitin as claimed in claim 1 is in the range 0.5% to 2%,
preferably 1%.
9) Diacerein as claimed in claim 1 is in the range 0.5% to 2%, preferably
1%.
10) Process of manufacture a formulation as claimed in claim in the
following manner:

PROCEDURE:-
A) AQUEOUS PHASE:
• Take 40 Kg of Purified water and add Sodium Meta-bisulphite stir to get dissolve.
• Add Glucosamine sulphate potassium chloride to above solution and stir to get clear solution.
• Now add xanthum Gum to above solution with stirring to obtained gel like mass.
• Now heat the above.mass at 40°C-50°C to about 30 minutes to get uniform mass.
B) NONAQUEOUS PHASE:
• Take Glyceryl Monostearate, Stearic acid, and Emulsifying wax in to SS container and heat to about 60°C-70°C to get uniform liquid phase.
• Add methyl paraben stir to get dissolve then add propyl paraben stir to get dissolve.
• Add capsaicin to above oil phase and stir to get dissolve.
• Now cool the above solution at 40°C. with constant stirring.
• Now add camphor and menthol with continuous stirring to get uniform.

• Transfer the non aqueous phase in to the aqueous phase with
constant stirring at 40°C.
C) DIACEREIN SOLUTION PREPERATION:
• Take Propylene Glycol and add Diacerein with constant stirring to get slurry (yellow color slurry) for 30 minutes.
• Now transfer above in above bulk.
• Make up the final weight with purified water up to 100 Kg.