DESCRIPTION
FIELD OF THE INVENTION
The present invention involve formulation and development of novel dosage form of antihistaminic drugs in gels form. The gels form is used for the various skin conditions include honey bees bite, itching of skin, utricaria/Hives and rosacea.
PRIOR ART OF THE INVENTION
A bee sting is a sting from a bee (honey bee,' bumblebee, sweat bee, etc. ) . The stings of most of these species can be quite painful,' and are therefore keenly avoided by many people.
Bee stings differ from insect bites, and the venom or toxin of stinging insects is quite different. Therefore, the body's reaction to a bee sting may differ significantly from one species to another. In particular, bee stings are acidic, whereas wasp stings are alkali. So the body's reaction to a bee sting may be very different than to that of a wasp sting.
The most aggressive stinging insects are vespid wasps (including bald-faced hornets and other yellow jackets) and hornets (especially the Asian giant hornet). All of these insects .aggressively defend their nests.
Although for most people a bee sting is painful but otherwise relatively harmless, in people with insect sting allergy., stings may trigger a dangerous anaphylactic reaction that is potentially deadly. Additionally, honey bee stings release pheromones that prompt other nearby bees to attack.

Hives also known as urticaria, is a kind of skin -rash with red, raised, itchy bumps. They may also burn or sting. Often the patches of rash move around. Typically they last a .few: days and do not leave any long-lasting, skin changes. Fewer than 5% of cases last for more than six weeks. The condition frequently . recurs. Hives frequently . occur following an infection or as a result of an allergic reaction.
Rosacea (rose-AY-sha) is a common skin disease. It often begins with a tendency to blush or flush more easily than other people.
The redness can slowly spread beyond the nose and cheeks to the forehead and chin. Even the ears, chest, and back can be red all the time. Rosacea can cause more than redness. There are so many signs and symptoms that- rosacea has four subtypes:',
Erythematotelangiectatic rosacea: ■ Redness, flushing, visible blood vessels.
Papulopustular rosacea: Redness, swelling, and acne-like breakouts.
Phymatous rosacea: Skin thickens and has a bumpy texture.
Ocular rosacea: Eyes ' red and irritated, eyelids can be swollen, and person may have what looks like a sty.
With time, people who have rosacea often see permanent redness in the center of their face.
Antihistamines are drugs which treat allergic rhinitis and
i other allergies. Antihistamines can give relief when a person
has nasal congestion, sneezing, or hives because of pollen,
dust mites, or animal allergy. Typically people take
antihistamines as an inexpensive, generic, over-the-counter
drug with few side effects. As an alternative to taking an
antihistamine, people who suffer from allergies can instead

avoid the substance which irritates them. Antihistamines are usually ■ for short-term treatment. [Chronic allergies increase the risk of health problems which antihistamines' might not treat, including asthma-, sinusitis, and lower respiratory tract infection.Doctors recommend that people talk to them before any longer term use of antihistamines.
Although typical people use the word "antihistamine" to describe drugs for treating allergies, doctors and scientists use the term to describe a class of drug that opposes the activity of histamine receptors in the body. In this sense of the word, antihistamines are sub classified according to the histamine, receptor that they act upon. The two largest classes of antihistamines are Hi-antihistamines and H2-antihistamines. Antihistamines that target the histamine Hl-receptor are used to treat allergic reactions in the nose (e.g., itching, runny nose, and sneezing) as well as for insomnia. They are sometimes also used to treat motion sickness or vertigo caused by problems with the inner ear. Antihistamines that target the histamine H2-receptor are used to treat gastric acid conditions (e.g., peptic ulcers and acid '" reflux). Hi-ant ihist amines work by binding to histamine Hi receptors in mast cells, smooth muscle, and endothelium in the body as well as in the tuberomammillary nucleus in the brain; H2-antihistamines bind to histamine H2 receptors in the upper gastrointestinal tract, primarily in the stomach.
Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at Histamine receptor.. Only a few currently marketed Hl-antihistamines are known to function as inverse agonists.

Histamine is a biogenic amine formed by decarboxylation of the amino acid histidine and is present as a tissue hormone in human', and..animal organisms, especially in the skin and in the lung. However, it is also contained in bee poison,' in the salivary secretion-of biting insects, in stinging nettles, and such like. In the human body, histamine is stored in the basophilic granulocytes and the mastocytes. When allergic skin reactions occur, excess histamine is released and is then one of the factors responsible for itching and the formation of skin weals and flares. This release takes place whenever human and (animal cells are damaged and causes reactions of the surrounding tissue. Even though histamine is rapidly metabolised in the human body, the effects caused by the release may last .for a considerable period of time which severely affects the . well-being of the person concerned. At present, antihistamines are primarily administered orally to treat these effects of histamine releases.
For example, HI antihistamines are typically administered orally and sometimes nasally in the form of a spray to treat hay fever.
OBJECTIVE OF THE INVENTION
The objective of present invention is to prepare topical gel of antihi.staminic drugs. It will provide the -drugs at the site of action and reduce systemic side .effects of the antihistaminic drugs.
SUMMARY OF THE INVENTION
The present invention relates to a pharmaceutical composition for topical application in the form of a gel, of a antihistamic pharmaceutically acceptable salts thereof as ^well as at least one pharmaceutical carrier or excipient which is a

solvent for the antihistamic drug. Other advantageous embodiment's of the invention.
DETAILED DESCRIPTION
The objective .-of present invention is to prepare topical gel of antihistaminic drugs. It' will provide the drugs at the site of action and reduce systemic side effects of the antihistaminic drugs.
It is one advantage of the topical application of the antihistamic in the form of a gel of the invention that the active ingredient counteracts the locally released histamine by binding . competitively to the relevant receptor so that symptoms may largely be avoid ed or reduced.
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1
The gels of the invention are preferably intended for the therapy -. of a disease or disorder selected from the group consisting of urticaria, allergy-based dermatoses (allergic skin reactions), atopical eczema, itching, redness, sunburn .and insect bites'.
The gels of the invention permit easy spreading on the skin, especially since these disorders tend to affect large areas, and may have a cooling effect perceived as pleasant by the patient. According to the invention, resorption may be accelerated by formulating the active' ingredient in a gel which is easily broken down and therefore releases said active ingredient on the skin more rapidly.
the pharmaceutical compositions of the antihistamic pharmaceutically acceptable
As described above, invention contain a salts.

In addition, the gels of the invention contain one or more pharmaceutical excipients or carriers. Such pharmaceutical excipients or carriers are preferably selected from pharmaceutical excipients and carriers, which are known and suitable for the formulation of the. above mentioned composition form. At least one of the excipients and carriers is a solvent for the active ingredient used. As possible pharmaceutical excipients and • carriers, mention may be made of solvents such as water, alcohols, especially C1-C5. alcohols such as ethanol, n-propanol, 2-propanol, isopropanol, t-butyl alcohol; ethers such as MTBE; ketones such as acetone, methyl ethyl ketone; humectants such as glycerol; glycols such as ethylene glycol, propylene glycol; emulsifiers such as lower, optionally polyhydric CI-5 alcohols partially esterified with long-chain (C12-C24) fatty acids such as glycerol •monostearate, isopropyl myristate, fatty acid ester of sugar alcohols .such as sorbitan mono-fatty acid ester, polyethoxylated derivatives of such compounds, polyethoxyethylene fatty acid ester and fatty alcohol' ether, cholesterol, cetyl stearyl alcohol, wool wax alcohols and synthetic surfactants with a low HLB value; solubilisers such as carbopol; low-viscosity paraffins, triglycerides; lipophilic substances such as isopropyl myristate; pH regulators such as TEA, carbonates and phosphates; chelating agents such as EDTA and salts thereof; as well as preservatives.
In .addition to these pharmaceutical excipients and carriers, the pharmaceutical compositions of the invention may contain one or more cosmetic excipients. Such cosmetic excipients are well known to pharmaceutical formulators. In particular, they may be selected from the group consisting, of humectants,

smoothing agents, UV filters, pigments, dyes, perfumes, vitamins and bleaching agents. Humectants, smoothing agents and perfumes are especially preferred.
As far as the gels to be used according to the invention are concerned, we must distinguish between hydrophilic gels and hydrophobic gels. In the invention, both may be used, optionally depending on the indication to be treated. As is well known, hydrophilic gels are gels having a high water content(80 to 90%).
The hydrophobic or so-called "oleogels" are greasing gels which are formed with liquid paraffins, polyethylene glycols, triglycerides etc. as the. base together with gelatinising agents such as highly dispersed silica or aluminum or zinc soaps. In the invention, hydrophilic gels are particularly well suited for the indications insect bites and sunburn, whereas oleogels are .specifically used for atopical eczema.
Example
Gel Preparation
A gel preparation was prepared from the following components by a conventional method:
Bepotastine Besilate 1.000 g
Carbopol 940 0.800 g
Diethanolamine 0 . 500 g
Potassium Sorbate 0.100 g *
Sodium Methyl Paraben 0.300 g
Sodium Propyl Paraben 0.030 g
EDTA Sodium . 0.020 g
Cremophor RH 40 3.000 g-

Propylene Glycol

10.000 g

Purified Water

Q.S. to lOOg

We claim,
1. A drug composition for topical application in the form of a
gel, comprising
0.05 to 5.0 wt.-% of a non-sedating antihistamine selected from the group consisting of Bepotastine thereof;
1.0- to 2.0 wt.-% of crosslinked polyacrylic acid polymers;
0 to 0.4 wt.-% of aminopolycarboxylic acid;
20 to 40 wt.-% of Primary alchol;
0.5 to 5.0 wt.-% of Potassium Sorbate;
0.2 to 10.0 wt.-% of Sodium Methyl Paraben;
0.01 to 5.0 wt.-% of Sodium Propyl Paraben;
0.01 to 5.0 wt.-% of Cremophor RH 40;and
water Qs 100%.
2. The composition' mentioned in claim 1 used for the disease or disorder of skin like urticaria, allergy-based dermatoses (allergic skin reactions) , atopical eczema, itching, redness, sunburn 'and insect bites.
3. A drug composition according to claim 1 also comprising one or more cosmetic adjuvants.