FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
PATENTS RULES, 2003
(COMPLETE SPECIFICATION)
TITLE - "A SUITABLE ORAL FORMULATION FOR INSTANT AND SUSTAINED RELEASE ACTION."
NAME OF APPLICANT: ZOTA HEALTH CARE LTD
ADDRESS OF APPLICANT- ZOTA HEALTH CARE LTD
ZOTA HOUSE,
2/896, HIRA MODI STREET, SAGRAMPURA, SURAT - 395002 (GUJARAT), INDIA.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION - An orally administrable sustained release dosage form includes granules of an active pharmaceutical formulation and more particularly to oral paracetamol sustained release formulation for providing extended therapeutically relief.
BACKGROUND OF THE INVENTION Many medical conditions are best treated by administration in such a way as to sustain its action over an extended period of time.
Many physiological factors influence both the gastrointestinal transit time and the release of a drug from a controlled release form and thus influence the uptake of the drug in to the systemic circulation.
Certain medical conditions are most desirably treated with a dosage form which provides both immediate therapeutic effects while reducing the number of doses necessary, thereby making therapy more convenient. Known examples of pharmaceutical formulation which provide both immediate and sustained release of an active pharmaceutical ingredient are disclosed in following patent/ patent applications.
According to EP1274402 (Bl) wherein a pharmaceutical composition comprising an immediate release phase and a sustained release phase of paracetamol is described which has a unique in vitro dissolution profile resulting in advantageous pharmacokinetic properties.
According to 7943170 wherein a pharmaceutical composition comprising an immediate release phase and a sustained release phase of paracetamol is described which has a unique in vitro dissolution profile resulting in advantageous pharmacokinetic properties.
According to Publication Number: 20070141144 wherein Gastric retentive dosage forms for extended release of acetaminophen or for both immediate and extended release of acetaminophen are described. The dosage forms allow effective pain relief upon once- or twice-daily dosing. Methods of treatment using the dosage forms and methods of making the dosage forms are also described.
According to Patent application number 20090311327 wherein The present, invention provides an oral delivery system for a therapeutic compound that is an acid, a salt of an acid or an

unionized compound or a proactive form thereof with pharmacological, physiological or biochemical activity. The present invention particularly provides a swallow formulation comprising a therapeutic compound that is an acid, a salt of an acid or an unionized compound or a proactive form thereof which facilitates the rapid delivery of the therapeutic compound to the circulatory system.
SUMMARY OF THE INVENTION
The present invention comprises a sustained or controlled release paracetamol granules and uncoated, quick release paracetamol granules pressed together in a tablet. Preferably the binding is water permeable, water insoluble, pH independent binding. Finally the invention alternatively encompasses paracetamol in sustained release form binding with said water permeable, water insoluble, pH independent binding.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with a first embodiment of the invention, a sustained or controlled release paracetamol formulation is provided. The paracetamol is preferably provided in a finally divided from such small granules. The paracetamol granules preferably have an average particle size which is suitable for medication. The paracetamol granules may contain excipients, adjuvant or other active ingredients in minor amounts if desired.
The sustained release paracetamol formulation in accordance with the first aspects of the invention are provided with a sustained release binding formulation comprising a water insoluble, water permeable and slightly water swellable polymer binding The polymeric binding not soluble in the gastroinstinal fluids and is not sensitive to the pH thereof.
Suitable excipients and adjuvants which can be used in the preparation of the sustained release or controlled release therapeutically composition of the present invention generally include those conventionally used in the pharmaceutical industry.
Bilayer sustained release (SR) tablets of formulation in which one layer release or disintegrate paracetamol 700 mg within 15 to 20 minutes & other layer will release or disintegrate paracetamol 300mg after 6 to 7 hours

For IR G LAYER (Immediate Releases Granules)
This layer comprises of main active ingredient such as Paracetamol and other excipients for example Starch, MCCP , PVP K-30 , Methyl Paraben, Propylparaben, Cross Carmelose sodium, SSG, Magnesium stearate , Talcum.
As per the embodiment polyvinylpyrrolidone (crospovidone) K 30 is used as a Disintegrant expand and dissolve when wet causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, facilitating dissolution.
Examples of disintegrates include Cross linked polymers such as cross linked polyvinylpyrrolidone (crospovidone), cross linked sodium carboxymethyl cellulose (croscarmellose sodium) another disintegrates is modified starch sodium starch glycolate.
As per the embodiment Magnesium stearate is used as a diluent and it has lubricating properties, preventing ingredients from sticking to manufacturing equipment during the compression of chemical powders into solid tablets; magnesium stearate is the most commonly used lubricant for tablets. Studies have shown that magnesium stearate may affect the release time of the active ingredients in tablets, but not that it reduces the over-all bioavailability of those ingredients.
As per the embodiment talc used as a Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall.
Common minerals like talc or silica, and fats, for example vegetable stearin, magnesium stearate are the most frequently used lubricants in tablets or hard gelatin capsules. Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics.
For S R G LAYER (Sustained Release Granules)
This layer comprises of main active ingredient such as Paracetamol and other excipients for example Starch, MCCP, Stearic Acid, Carnauba Wax, Ethyl Cellulose, Magnesium stearate

As per the embodiment Carnauba wax is used as a tablet-binding agent. Adding the carnuaba wax aids in the Complex binding of the paracetamol for the desired release pattern.
As per the embodiment Ethyl cellulose is mainly used as a Complex binding agent for release pattern. Ethylcellulose is an inert, hydrophobic polymer and is essentially tasteless, odorless, colorless, noncaloric, and physiologically inert. It has been extensively used as a pharmaceutical vehicle in a number of dosage forms. It has been used as a binding material for tablets and granules, as a tablet binder, in preparing microcapsules and microspheres and also as film- and matrix-forming material for sustained-release dosage forms.
As per the embodiment stearic acid this is also used for the complex binding, all three together make the complex of sustained release granules.
As per the embodiment Magnesium stearate is used as a diluent and it has lubricating properties, preventing ingredients from sticking to manufacturing equipment during the compression of chemical powders into solid tablets; magnesium stearate is the most commonly used lubricant for tablets. Studies have shown that magnesium stearate may affect the release time of the active ingredients in tablets. But not that it reduces the over-all bioavailability of those ingredients.
As per the embodiment starch is used in granulated formulation processes can be more effective if used both "intragranularly" and "extra granularly" thereby acting to break the tablet up into granules and having the granules further disintegrate to release the drug substance into solution. However, the portion of disintegrant added intragranularly (in wet granulation processes) is usually not as effective as that added extra granularly due to the fact that it is exposed to wetting and drying (as part of the granulation process) which reduces the activity of the disintegrant. Since a compaction process does not involve its exposure to wetting and drying, the disintegrant used intragranularly tends to retain good disintegration activity.
"Pregelatinized starch is a directly compressible form of starch consisting of intact and partially hydrolyzed ruptured starch grains. Pregelatinized starch has multiple uses in formulations as a binder, filler and disintegrant. As a disintegrant, its effective use concentration is between 5-10%. It's major mechanism of action as a disintegrant is thought to be through swelling."

As per the embodiment MCCP (Micro crystalline cellulose powder) is used in all methods of tableting, it is most effectively used for the better formulation like disintegrstion and dissolution of the products.
Manufacturing Process
For the preparation of IRG Layer
1. According to requirement, all raw materials sifted through appropriate sieve.
2. Paracetamol, starch, MCCP (Micro crystalline cellulose powder) are mixed for 15 minutes.
3. PVP K30, Methyl Paraben, propyl Paraben are used for binding procedure.
4. Cross Carmelose sodium, SSG, Magnesium stearate and Talcum are used for lubrication and disntrigation
For the preparation of SRG layer
1. Paracetamol, Starch, MCCP mixed the materials for 15 minutes in mixture and collected in PVC bag.
2. Steric, Carnauba Wax, Ethyl Cellulose are loaded in steam jacketed PLM, melt the material, with continue stirring.
3. Added the step first material to second step dough like mass obtained.
4. Removed the mat in tray make layer, cut in small piece.
5. Milled the small pieces in multimillion for granule.
6. Lubricate the granule for compression.

Sustained release dosage forms can also be used beneficially in the administration of relevant treatment.
Dosage forms should therefore be designed so that such variable factors do not release the active pharmaceutical ingredient at a controlled rate such that the amount of active pharmaceutical ingredient which is available in the body to treat the condition is maintained at a relatively constant level over an extended period of time.
The release of active pharmaceutical ingredients from a controlled release dosage form is generally controlled either by diffusion through a binding, by diffusion of the agent from a monolithic device, or by erosion of a coating by a process which is dependent upon enzymes or pH. because such factors can from time to time for a particular individual, and can from one individual to another sustained release pharmaceutical formulation do not provide a reproducible rate of release of the active pharmaceutical ingredient and thus do not minimize intra subject and inter subject variation in bioavailability of the active ingredient.
A two layer paracetamol tablet is available in which one layer is comprised of quick release paracetamol granules and the other layer is comprised of sustained release paracetamol which is release after some time.
Two compression steps are required to make the tablet, and the sustained release binding is pH dependent.
The Initial dose will be booster dose such as 700 mg and later dose of 300 mg will be maintenance dose and it will be single dose only but tablet will be bilayered, first layer of 700 mg will be disintegrate within 15-20 minutes and second layer will be after 6 to 7 hours.

I R G LAYER

S.NO. INGREDIENTS QT IN
mg. Properties
1 Paracetamol 500 Dry mixing
2 Starch 15 Dry mixing
3 MCCP 14 Dry mixing
4 PVP K-30 4 Binder
5 Methyl Paraben 0.5 Binder
6 Methyl Paraben 0.05 Binder
7 Starch 30 Binder
8 Cross Carmelose sodium 8 Lubricant & disintigrant
9 SSG 4 Lubricant & disintigrant
10 Mag stearate 5 Lubricant & disintigrant
11 Talcum 5 Lubricant & disintigrant

S R G LAYER

S.NO. INGREDIENTS QT IN
mg. Properties
1 Paracetamol 500 Dry mixing
2 Starch 15 Dry mixing
3 MCCP 14 Dry mixing
4 Steric acid 20 Binder
5 Carnauba Wax 10 Binder
6 Ethyl Cellulose 5 Binder
7 Mag stearate 10 Lubricant

CLAIMS,
We Claims,
1. An orally administrable sustained release dosage of paracetamol.
2. An orally administrable sustained release dosage comprises bilayer tablet form, one layer is comprised of quick release paracetamol granules and the other layer is comprised of sustained release paracetamol which is release after some time.
3. An orally administrable sustained release dosage claimed as claim 2 wherein The Initial dose will be booster dose such as 700 mg and later dose of 300 mg will be maintenance dose.
4. An orally administrable sustained release dosage claimed as claim 2 wherein it is single dose only but tablet will be bilayered, first layer of 700 mg will be disintegrate within 15 -20 minutes and second layer will be after 6 to 7 hours.