FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION (See section 10 and rule 13)
1. TITLE OF THE INVENTION
MANUFACTURING PROCESS OF PARACETAMOL EFFERVESCENT TABLETS
2. APPLICANT(S)
(a) NAME: RAJAT PHARMACHEM LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Rajat Pharmachem Ltd
B/202, Gayatri Darshan, Thakur Complex, Kandivali (E), Mumbai-400 101, India
3. PREAMBLE TO THE DESCRIPTION
COMPLETE
The following specification particularly describes the invention and the manner in which is to be performed.
4. DESCRIPTION (Description shall start from next stage.)
Attached
5. CLAIMS (Not applicable for provisional specification. Claims should start with the
preamble - "I/We claim" on separate page)
. Attached
6. DATE AND SIGNATURE (to be given at the end of last page of specification)
7. ABSTRACT OF THE INVENTION (to be given along with complete specification
on separate page)
Attached
Note:-
* Repeat boxes in case of more than one entry.
*To be signed by the applicant(s) or by authorized registered patent agent.
*Name of the applicant should be given in full, family name in the beginning.
*Complete address of the applicant should be given stating the postal index no./code,
state and country.
*Strike out the column(s) which is/are not applicable.

DESCRIPTIONS 1. TITLE OF INVENTION
(MANUFACTURING PROCESS OF PARACETAMOL EFFERVESCENT TABLETS)
The effervescent products gained much importance with the technology of Alka Seltzer. These mixtures have been moderately popular over the years since along with medicinal activity they are attractive dosage form for the patients. Effervescent reactions have been used alternatively preparation of other dosage forms, such as suppositories (for laxative effect), vaginal suppositories (for contraceptive effect) and drug delivery system.
Effervescence has also proved its utility as an oral drug delivery system in the pharmaceutical and dietary industries for decades.
A wide range of effervescent tablets have been formulated over the years. These include dental compositions containing enzymes, contact lens cleaners, washing powder compositions, beverage sweetening tablets, chewable dentifrice, dental cleansers, surgical instrument sterilizers, analgesics and effervescent candies as well as many preparations of prescription pharmaceuticals such as antibiotics, ergotamines, digoxin, methadone and L-dopa. Preparations for veterinary use have also been develop.
Fust onset of action
Soluble effervescent tablets are prepared by compression. In adition to active ingredients, they contain mixtures of acids (like citric, tartaric, malic and fumaric acid) and carbonates like sodium, potassium bicarbonate that release carbon dioxide when dissolved in water.
Storage:
Effervescent products should be stored in tightly closed containers or moisture proof packs. They should be preserved in air tight containers and protected from excessive moisture. Dessicants are usually added to the containers.
Labeling:
It should be labeled that these products are not to be swallowed directly. The label should state that when the tablets are packaged in individual pouches, the label instructs the not to open until time of use. The label also states that the tabletsare to be dissolved in water before being taken.

EFFERVESCENT REACTION
Effervescence is the evolution of gas bubbles from a liquid, as the result of a chemical reaction. The most common reaction for pharmaceutical purpose is the acid base reaction between sodium bicarbonate and citric acid. Acid-base reaction between alkali metal bicarbonate and citric or tartaric acid has been used for many years to produce pharmaceutical preparations that effervescence as soon as water is added.
3NaHC03(aq) + H3C6H507(aq) 3H20 + C02 + 3Na3C6H507(aq)
This reaction starts in presence of water, even with small amount as catalyzing agent, and because water is one of the reaction products, it will accelerate the rate of reaction, leading to difficulty in stopping the reaction. For this reason, the whole manufacturing and storage of effervescent products is planned by minimizing the contact with water. The physical and chemical basis of the formulation depends on essentially the total dissolution of bicarbonate salts and the acids prior to formation of free acids.
2. FIELD OF INVENTION
The present invention relates to a novel pharmaceutical preparation of Effervescent of soluble Paracetamol Tablets B.P. 1000 mg in the form of effervescent dosage form which comprises Paracetamol as pharmaceutically active substances, i.e. the drug.
More specifically, the invention relates to a new effervescent dosage form comprising individual unit, which dissolves when they are liberated in aqueous effervescent solution. This new effervescent dosage form comprises for instance unit of an acid susceptible substance furthermore, the present invention refers to a method for the manufacture of such dosage form and, to the use dosage form in medicine.
3. BACKGROUND OF INVENTION
Effervescent dosage forms are one possible medium for administration of drugs. Effervescence may be used to provide some degree of taste-masking. Prior to administration to a patient, an effervescent composition is dissolved and / or / dispersed in e.g. an aqueous medium, such as drinking water. Dissolution and / or dispersion take place directly or rapidly, with effervescence to give an agreeable presentation of the drug in the form of a solution which is suitable to drink. Effervescent dosage forms are particularly suitable for patients finding difficulty in swallowing tablets or disliking tablets.

Some examples of different effervescent tablets and systems described in the prior art are discussed below.
Effervescent tablets containing acid-sensitive agents have previously been lmade by coating the acid particles in the acid-base couple with base to separate the acid-sensitive agent from the acid, effervescent tablets containing the active substance without any coating layer.
The expandable controlled release dosage from using gas development in a dosage form. The tablet swells to such a size that it says for a prolonged time in the stomach by utilizing the gas generated after ingestion of the tablet.
Advantages of Effervescent Tablets
1, Fast onset of action
a. Effervescent tablets have major advantage that the drug product is already in
solution at the time it is consumed. Thus, the absorption is faster and more
complete than with conventional tablet.
b. Faster absorption means faster onset of action, critical in treating acute symptoms
such as pain.
c. Buffered preparation with adjustable stomach pH optimizes formula performance
characteristics. Effervescent products allow for very fast absorption into the blood
stream due to the effect of the buffered drink on the stomach. In short, the
stomach empties much more quickly into the small intestine, where the majority
of ingredients are absorbed.
d. Effervescent dietary supplements and drugs are delivered to the stomach at a pH
that is just right for absorption.
e. Many dietary supplements and medications travel slowly through the
gastrointestinal tract or have absorption that is hampered by food or other
chemicals. To achieve desired absorption levels, such dietary supplements or
drugs are often administered as injections or with increased dosages.
2. No need to swallow tablets
Effervescent medications are administered in liquid form so they are easy to take as compared to tablets. The number of people who cannot swallow tablets or who dislike swallowing tablets is growing. Many diseased conditions require the patient or customer to swallow several tablets at a time. The elderly, in particular, have difficulty in swallowing tablets. With an effervescent dosage form, one dose can usually be delivered in just 3 or 4 ounces of water. The amount used when someone swallows a conventional tablet.

3. Good stomach and intestinal tolerance
Effervescent tablets dissolve full in a buffered solution. Reduced localized contact in the upper gastrointestinal tract leads to less irritation and greater tolerability. Buffering also prevents gastric acids from interacting with the drug themselves, which can be a major cause of stomach and esophageal upsets. Dietary supplements taken in "liquid effervescent form" are easily digested as opposed to traditional pill or tablet due to breakdown of molecular structure. Consequently, effervescent technology offers 100 % absorption due to breakdown of large molecules into small more easily digestible ones.
4. More portability
Effervescent tablets are more easily transported than liquid medication because no water is added until it's ready to use.
5. Improved palatability
Drugs delivered with the effervescent base, taste better than most liquids, mixtures and suspensions. Superior taste masking is achieved by limiting objectionable characteristics and complementing formulations with flavors and fragrances. Effervescent pharmaceuticals retain their flavor after lengthy storage. The effervescent tablets essentially include flavorings so they taste much better than a mixture of a non-effervescent powder in water. Moreover, they produce fizzy tablets, which may have better consumer appeal than the traditional dosage forms.
6. Superior stability
Excellent stability is inherent with effervescent formulations, particularly surpassing liquid forms.
7. More consistent response
Drugs delivered using effervescent technology have predictable and reproducible pharmacokinetic profiles that are much more consistent than tablets or capsules.
8. Incorporation of large amounts of active ingredients
In many cases, one effervescent tablet will equal to three conventional tablets in active dose amounts.
9. Acute dosing
Researchers have shown that effervescent tablets enhance the absorption of a number of active ingredients (e.g. disulfiram and caffeine), compared to conventional formulations. This is because the carbon dioxide created by the effervescent reaction can induce enhanced active ingredient permeability due to an alteration of the paracellular pathway. The paracellular pathway is the primary route of absorption for hydrophilic active ingredients in which the solutes diffuse into intercellular space between epithelial cells. It is postulated that the carbon dioxide widens the intercellular space between cells, which leads to greater absorption of active ingredients (both hydrophobic and hydrophilic). The

increased absorption of hydrophobic active ingredients could be due to the non-polar carbon dioxide gas molecules partition into the cell membrane, thus creating an increased hydrophobic environment, which would allow, the hydrophobic active ingredients to be absorbed. 10. Improved therapeutic effect
The effervescent components aid in improving the therapeutic profiles of the active ingredients. They also help in solubilization of poorly soluble drugs. Conventional tablets are often associate with slower onset of action and also undergoes first pass metabolism. Effervescent tablets avoid the first pass metabolism and also produce rapid onset of action.
Other Effervescent Considerations
1. Easier and more convenient than other liquid products to administer.
2. Less chance of misuse.
3. Ability to combine multiple active ingredients, if therapeutically appropriate.
4. The incorporation of large amounts of ingredients. A properly prepared effervescent tablet or powder can allow a large dose of ingredients to be taken in a single serving. The organic food acid combines with the carbonate source to form potassium, Na, Ca or Mg salts and buffers the solution to a normal pH, and so it is easy on the stomach.
5. No need to swallow tablets.
6. The product is typically self-mixing and flavorful.
7. The inefficient and difficult absorption of the traditional pill or tablet also leads to stomach discomfort and distress.
8. Effervescent technology is excellent for a sensitive digestive track system.
The elderly, many supplement's dosages require several tablets to be swallowed at one time. The elderly, in particular, have more difficulty swallowing tablets as they age. With an effervescent system, one dose can usually be delivered in just three to four ounces of water, which is about what someone would need to swallow to take a conventional tablet. Additionally, after the age of 40, our digestive system becomes less efficient as years passes by.

CLAIMS
We claim:
1. A process for the manufacture of Paracetamol effervescent tablets in which the powdered raw materials are mixed and the mixture is carefully granulated and dried, wherein the steps of mixing said raw materials and granulation are conducted inside the same apparatus, wherein the drying step is performed in Tray Dryer. The dried granules are lubricated in the blender and directly subjected to compression.
2. The process of claim 1, wherein the components of the mixture are:
a. Paracetamol
b. Sodium bicarbonate
c. Citric acid
d. Povidone (PVP K 30)
e. Sodium Saccharin
f. Sodium Carbonate
g. Methylene Dichloride
h. Simethicone
i. Polysorbate 80 A process for the manufacture of effervescent tablets from a plurality of powdered raw materials, with the avoidance of external contamination, said process comprising the steps of:
a. Transferring said raw materials into rapid mixer granulator after sifting the
material.
b. Add binder (prepared by adding of sodium saccharin into purified water) into the
granulator and allowed to mixed and prepare granules.
c. Transfer granules in the tray dryer and allow to dry and to stabilize it till 12 hrs.
d. Dried granules blended with lubricant materials.
i. Aspartame which is also used as sweetening agent. ii. Flavoring agent
e. Lubricated material is directly subjected to compression.
3. The flavoring agent used in claim 2 is any one of the following agents.
a. Lemon flavor
b. Orange flavor
c. Pineapple flavor
d. Strawberry flavor
e. Raspberry flavor
f. Lime flavor
4. The effervescent composition manufactured according to claim 2.
5. The compressed effervescent tablet according to claim 2 containing,
a. Paracetamol 500 mg
6. The compressed effervescent tablet according to claim 2 containing,
a. Paracetamol 1000 mg