FIELD OF THE INVENTION
The present invention relates to an extended release tablet dosage form of Metoprolol succinate and a process for preparation thereof.
BACKGROUND OF THE INVENTION
Metoprolol is a selective betai adrenoceptor blocking agent, used in the treatment of cardiovascular system, especially for the treatment of hypertension and is available in the form of tartrate and succinate salts. Metoprolol tartrate is available in the USA as immediate release tablets for oral administration and in ampuls for intravenous administration. Metoprolol succinate is available in the USA as extended release, tablets for oral administration.
Metoprolol has a very low melting point, tartrate around 120°C. succinate around 136 °C. Because of this, metoprolol is always manufactured in a salt-based solution, as drugs with low meliing points are difficult to work within a manufacturing environment. Metoprolol free base exists as a waxy white solid, and the tartrate salt is liner crystalline material. Metoprolol succinate is a white crystalline powder with a molecular weight of 652.8.
Metoprolol succinate is classified as BCS (Biopharmaceutics Classification System) class 1 drug which is highly soluble and has high permeability and is well absorbed and its absorption rate is higher than excretion. It is freely soluble in water; soluble in methanol; sparingly soluble in ethanol; slightly soluble in dichloromethane and 2-propanol; practically insoluble in ethyl-acetate, acetone, diethylether and heptane.
Metoprolol is metabolized in the liver to inactive metabolite and undergoes a-hydroxylatton and O-demethylation as a substrate of the cytochrome liver enzymes CYP2D6 and a small percentage by CYP3A4.
In the US. Metoprolol succinate is marketed under the brand name Toprol-XL®. TOPROL-XL® is an extended-release tablet and intended for once daily

administration. The tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug deliver}' unit and is designed to deliver metoprolol continuously over the dosage interval. The tablets contain 23.75. 47.5, 95 and 190 mg of metoprolol succinate equivalent to 25, 50, 100 and 200 mg of metoprolol tartrate, USP, respectively. Inactive Ingredients in Toprol XL© include silicon dioxide, sodium stearyl fumarate, polyethylene glycols, titanium dioxide, paraffin, and hypromethylcellulloses.
US patent No. 4.927..640 describes a composition which requires beads that are selected from the group consisting of glass and silicon dioxide and which are insoluble in water, physiological fluids and liquids commonly used for intravenous infusion. These beads are covered with one or more pharmaceutically active compounds and a release controlling polymeric membrane covering the active layer.
US patent No. 4.957,745 describes a controlled release preparation comprising a plurality of beads having a soluble component comprising at least 95% weight/weight of a metoprolol salt. The controlling polymeric membrane is described as consisting essentially of ethylcellulose, or a mixture of ethylcellulose and hydroxypropyl-methylcellulose. This patent exemplifies metoprolol salt applied on silicon dioxide beads, which beads are sized between I50um - 250pm.
US Patent No. 5,081.154 is directed to metoprolol succinate in an oral composition coated with an anionic polymer, soluble at pH over 5.5 and a water insoluble quaternary ammonium substituted acrylic polymer.
US patent No. 5.246.714 describes a composition and method for the preparation of beads containing a pharmaceutically active ingredient compressed into tablets.
US patent No. 8,815.285 describes an extended release dosage forms of metoprolol succinate comprising an inert core, comprising mierocrystalline cellulose spheres, coated with one or more water insoluble pharmaceutically acceptable polymers, the

inert core further comprise one or more coatings with one or more pharmaceutical ly active ingredients and other pharmaceutical!)' acceptable excipients, which is optionally coaled with one or more release controlling polymers.
US Patent No. 9.561,187 describes an extended-release drug composition comprising a monolithic matrix tablet comprising Metoprolol containing granules and extra granular excipients, wherein the granules comprise about: 20-30% of a Metoprolol selected from the group consisting of Metoprolol succinate and Metoprolol tartrate; 5-10% dibasic calcium phosphate; 5-10% lactose monohydrate; 5-10% Pregelatinized starch acetate; and 1-5% hydroxy I ethyl cellulose; and wherein the extra granular excipients comprise about: 5-15% carbomer homopolymer; 5-15% polyethylene oxide: 10-20% hypromellose; and 5-10% methacrylic acid copolymer.
US 2007/0053983A1 describes an oral composition comprising: a therapeutically effective amount of Metoprolol succinate and a hydrophilic polymer matrix comprised of gelling agents which include at least one hydrophilic polymer with one or more gum or gum derivative and pharmaceutically acceptable excipients therefore wherein said composition provides a sustained or modified release of Metoprolol succinate or a pharmaceutically acceptable derivative thereof.
US 2007/0202172 describes a pharmaceutical composition for extended release comprising pellets coated with an active pharmaceutical ingredient wherein each coated pellet comprises a) an inert core comprising at least about 50% (w/w) of soluble substance; b) a drug layer comprising the active pharmaceutical ingredient, which layer covers the inert core: and c) a controlled release layer thereon, without using inherently toxic solvents. Preferably, a sub-coat layer covers an initial core/sphere forming the inert core.
US 2009/0324717 describes an extended release coated granule comprising a granule having a particle size ranging from 0.2 to 2 mm. a friability lower than or equal to 1% and comprising Metoprolol succinate as active ingredient in an amount ranging from

10 to 75% by weight of the granule and at least one binder selected from one or both of niicrocrystalline cellulose and methyicelluiose, said granule being coated with a film-former coating agent.
EP 2255791A1 describes a process for the manufacture of an extended release pharmaceutical composition comprising a granule comprising Metoprolol succinate and at least two pharmaceutical^' acceptable excipients, wherein one pharmaceutical^ acceptable excipient is an extended release agent; the second pharmaceutical^ acceptable excipient is selected from a binder, a diluent and mixtures thereof; and Metoprolol succinate is in a crystalline form having a D50 ranging from 5 to 16 microns and a D90 below 50 microns, wherein the final granule or spheronized granule is further mixed with at least one pharmaceutically acceptable excipient and compressed to form a tablet, and preferably the tablet is coated.
WO 2005/084636A2 describes an oral controlled-release pharmaceutical composition of Metoprolol succinate comprising a plurality of beads comprising a) a water soluble, water sweilable or water-insoluble inerl core; b) one or more drug layers comprising Metoprolol: and c) one or more polymeric coatings surrounding the one or more drug layers.
WO 2012/052834A2 describes an extended release composition comprising Metoprolol or its pharmaceutically acceptable salts thereof wherein the composition comprises extended release pellet comprising: a) a water soluble or water sweilable inert core: b) the drug layer consisting of Metoprolol or its pharmaceutically acceptable salts thereof coated on the said core to obtain drug pellets: c) an extended release polymer layer comprising at least one water insoluble polymer selected from polymethacrylates, cellulose ethers, cellulose esters, or mixtures thereof to form extended release pellets: and a tablet excipient comprising at least two grades of niicrocrystalline cellulose wherein the dissolution profile of the extended release pellets remains substantially unaffected on compression into tablets.

The major problem associated with extended release tablets of Metoprolol succinate is consistency in dissolution profile, breakage of the extended release coat during the compression.
OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide extended release tablets of Metoprolol succinate which are bioequivalent to the commercially available tablets, prepared using simple and commercially feasible method.
SUMMARY OF THE INVENTION
The present invention provides an oral extended tablets of Metoprolol succinate, which comprises:
a) an inert core comprising at least about 10 to 20% (w/w) of dosage form;
b) a drug layer comprising Metoprolol succinate, coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising at least one water insoluble polymer and one binder to form extended release pellets;
d) cushioning layer coated on the extended release pellets applied using high shear mixer and
e) at least one tablet excipient.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides an oral extended release tablet dosage form of Metoprolol succinate, prepared by a process which comprises use of fluid bed process / granulation and high shear mixer granulalor.
Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes., as well as a number that is near to or approximately the number that the term precedes.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the methods belong.
Where a range of values is provided, it is understood that each intervening value between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the methods and compositions of the present invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within by the methods and compositions, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the methods and compositions.
It is appreciated that certain components or features, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the compositions and methods, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.
Jt is noted that, as used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.
It is noted that, as used herein the terms "solid dosage form" or tablet(s) or tablet dosage form is interchangeable.
As used herein, the term "comprises" or "comprising" permits the presence of one or more additional components in the compositions.

"Relative standard deviation" or "RSD," as used herein, refers to a measurement of how precise each measurement of blend uniformity or content uniformity is, i.e., how much each individual unit deviates from the group.
"Blend uniformity," as used herein, refers to the homogeneity of granulate including Metoprolol succinate pellets before tablet formulation, and can represent either one sample or the average of more than one sample.
The content uniformity of the tablets of the present invention is between 95% and 115% and blend uniformity is between 95% and 105% and the relative standard deviation of the blend uniformity is less than 2%.
The present invention provides oral extended tablets of Metoprolol succinate, which comprises preparing extended release drug loaded pellets using fluid bed processor and applying cushioning layer using high shear mixer granulator, followed by compressing the pellets into tablets.
As used herein the term "inert core" refers to a pharmaceutically acceptable core which core is inert and which is commercially available and may be water insoluble such as silicon dioxide, water svvellable such as microcrystalline cellulose spheres or water soluble such as lactose beads. The inert core may have been modified by for example by applying a sub-coat onto the core.
Suitable water insoluble polymer for preparing extended release coated pellets according to the present invention are selected from ethyl cellulose, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, hydroxypropylmethyl acetate succinate, cellulose acetate, poly(methacrylic acid, poly(methacrylic acid, ethyl acrylate) 1:1, poly(ethyl acrylate, methyl methacrylate) 2:1, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1 :2:0.2, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.1, methyl methacrylate)! :1, poly(methacrylic acid,

methyl methacrylate)l:2, and the like or mixtures thereof. The water insoluble polymer is present in the range from about 5 to 15% w/w of the tablets.
The extended release polymeric layer comprises binder selected from hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methylcellulose, povidone and the like or mixture thereof. The extended release polymeric layer may further comprise plasticizers such as triethyl citrate, dibutyl sebacate, propylene glycol and polyethylene glycol and the like.
The drug layer and extended release coat can be applied onto the inert core by spray coating in a conventional coating pan or fluidized bed processor or dip coating. The inert core(s) is coated by spraying drug solution or suspension prepared by dissolving or dispersing Metoprolol succinate and binders such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methylcellulose, povidone and the like or mixture thereof in a solvent such as such as methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, water and the like or mixture thereof.
The extended release coating is applied on the drug loaded pellets by spraying extended release polymer solution or suspension prepared by dissolving or dispersing at least one water insoluble polymer and one binder in a solvent such as methylene, chloride isopropyl alcohol, acetone, methanol, ethanol. water and the like or mixture thereof.
The present invention includes transforming extended release polymer coated pellets of Metoprolol succinate, into a homogenous granulate under shear conditions which do not degrade the pellets. For purposes of the present invention, the shear conditions under cushioning layer is applied on the extended release polymer coated pellets is generally be described as a set of conditions including a combination of temperature and mechanical forces .which permit the formation of the cushioning layer and homogenous granulate but do not break down during the compression process. The cushioning layer is applied using Rapid Mixer Granulator (RMG). This RMG

machine is also known in Industry with various key terms such as High shear granulation machine, Dry Powder granulator, Wet Granulator, Pharma Saizoner, High shear mixer granulator, High Shear Mixer Granulators, Granulator, Granulation Machine, Rapid Mixer Granulator.
In another aspect, the cushioning layer applied on the extended release pellets or extended release polymer coated pellets comprises water soluble polymer selected from polyethylene glycol for example commercially marketed as Macrogol, such as macrogol 3350: macrogol 4000 or macrogol 6000; binder such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, povidone and the like or mixture thereof. The water soluble polymer and binder is present in the range from about 5 to 15% w/w of the tablets.
In another aspect, the extended release pellets or extended release polymer coated pellets are blended with one or more excipients before applying the cushioning layer, such as diluents, disintegrants selected from microcrystalline cellulose (MCC). lactose, crospovidone. sodium starch glycolate,, croscarmellose sodium and the like or mixture thereof. The amount of excipients used for blending with extended release coated pellets may range from 20 to 30% w/w of the tablet dosage form.
In another aspect, the present invention provides determining the blend uniformity of the granulate(s). The compression of pellets coated with cushion layer is carried out only if the blend uniformity of the granulate(s) satisfies a predetermined criteria.
The present invention provides an oral extended release solid dosage form of Metoprolol succinate, which comprises:
a) an inert core comprising at least about 10 to 20% (w/w) of dosage form;
b) a drug layer comprising Metoprolol succinate, coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising at least one water insoluble polymer and one binder to form extended release pellets;

d) cushioning layer comprising 5 to 15% w/w coated on the extended release pellets, applied using high shear mixer granulator and
e) at least one tablet excipient.
In one aspect of the present invention, the inert core is coated with a solution or suspension comprising Metoprolol succinate, Opadry and suitable a solvent, in a fluid bed processor at optimum parameters. The drug layer is coated in a fluid bed processor at optimized parameters with an extended release coat. The cushioning layer is applied using rapid mixer granulator.
In yet another embodiment the present invention provides an oral extended release table dosage form of Metoprolol succinate, prepared by a process which comprises the steps of:
a) applying a drug layer comprising Metoprolol succinate on inert core of least about 10 lo 20% (w/w) of dosage form, to obtain drug loaded pellets using fluid bed process, b") applying an extended release polymer layer comprising at least one water insoluble polymer to form extended release pellets using fluid bed processor;
c) applying a cushioning layer on the extended release pellets using high shear mixer granulator and
d) blending the pellets obtained in step (c) with tablelliug excipients and
e) lubricating and compressing the blend obtained in step (d) to obtain extended release tablets.
Suitable tablet excipient comprises diluents, disintegrates, binders, glidants. lubricants and the like. Suitable diluents selected from lactose, microcrystalline cellulose, mannitol. starch, modified starch, Slarlac® (a spray-dried compound consisting of 85% alpha-lactose monohydrate and 15% maize starch dry matter available from Meggle). or mixtures thereof, disintegrants such as microcrystalline cellulose, crospovidone, sodium starch glycolate and the like; lubricants selected from magnesium stearate, stearic acid, sodium Stearyl fumarate. glyceryl behenate, talc, zinc stearate, silicon dioxide and the like.

In a preferred aspect, the present invention provides an oral extended tablets of Metoprolol succinate, comprising:
a) an inert core of microcrystalline cellulose spheres comprising at least about 10 to
20% (w/w) of dosage form;
b) a drug layer comprising Metoprolol succinate and a binder selected from
hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methylcellulose or
povidone coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising at least one water insoluble polymer
and one binder in an amount from about 5 to 15% w/w of the tablets, to form extended,
release pellets:
d) 20 to 35% w/w of the tablet dosage form a cushioning layer comprising
polyethylene glycol and binder, coated on the extended release pellets applied using
high shear mixer granulator and
e) ai least one tablet excipient.
In yet another preferred aspect, the present invention provides an oral extended tablets of Metoprolol succinate, which comprises:
a) an inert core of microcrystalline cellulose spheres comprising at least about 10 to 20% (w/w) of dosage form;
b) a drug layer comprising Metoprolol succinate and hydroxypropyl methyl cellulose, coated on the said inert core to obtain drug loaded pellets:
c) an extended release polymer layer comprising 5 to 15% w/w of ethylcellulose and hypromellose to form extended release pellets;
d) 20 to 35% w/w of the tablet dosage form a cushioning layer comprising
polyethylene glycol and hypromellose coated, on the extended release pellets blended
with microcrystalline cellulose and crospovidone. using high shear mixer granulator
and
e) tableting excipients comprising microcrystalline cellulose, crospovidone, colloidal
silicon dioxide and sodium Stearyl fumarate.

hi an embodiment, the extended release tablets preferably have a dissolution profile such that after 8 hours between abouf 20% and about 50% of the drug substance is dissolved when a sample equivalent to the desired dose is tested using USP apparatus type 1 :Method: Paddle (50 rpm medium: 500 ml 0.05M, Phosphate Buffer USP pH-6.8 at 37° C,
The present invention also provides an oral extended release solid dosage form of Metoprolol succinate, prepared by a process which comprises the use of combination of fluid bed process / granulation and high shear mixer granulator.
The inert core of each of the pellets in the pharmaceutical composition of the present invention comprises from about 50% to about 100% (per weight) of water swellable or water insoluble substance. A preferred inert core of the present invention comprises a sugar sphere, microcrystalline cellulose sphere or silicon dioxide beads. Sugar spheres used in pharmaceutical compositions generally contain no more than 92% of sucrose, calculated on the dried basis: the remainder consisting of maize starch. Commonly inert with a core size between about 50|im and about 500um, preferably between about 100 and about 400um. more preferably from about 250um to about 350um is used.
In the present invention the inert core may comprises an initial core/sphere that is sub-coated with a layer of a piasticized film coating polymer. This sub-coating provides physical strength to the inert core. The film coating polymer may be a hydrophobic or a hydrophilic polymer, or a combination thereof may be a cellulose polymer or polymethacrylate polymers and contain plasticizers such as triethyl citrate, polyethylene glycol, dibutyl sebacate, and dibutyl phthalate. to plasticize the film coating polymers. The sub coat is mixed with solvents selected from ethanol, isopropyl alcohol, acetone and purified water prior to their application onto the inert core.

The cushioning layer according to the present invention is applied on the extended release layer using high shear rapid mixer granulator (RMG). without affecting the strength of pellets. This is simple, robust and easily reproducible. The extended release coated pellets are blended with diluents and disintegrants such as microcrystalline cellulose and crospovidone in order to have cushioning effect between extended release coat and cushion layer.
The present invention provides an oral extended release solid dosage form of Metoprolol succinate, prepared by a process which comprises the use of fluid bed process / granulation and high shear mixer granulator.
The extended release tablet may be cosmetically coated with commercially available tablet film coating agents such as for example Opadry®.
The present disclosure is further described with reference to the following examples, which are provided to illustrate the invention and are merely for illustrative purpose only and should not be construed to limit the scope of the invention.

Manufacturing Process Drug Loading:
1. hypromellose was added to water under stirring,
2. Mctoprolol Succinate was added to this solution under stirring,
3. Core MCC pellets were loaded in Fluid Bed Equipment (FBE) bowl and coated using above prepared Metoprolol Succinate solution and obtained pellets were dried.
Polymer coating
1. hydroxypropyl cellulose was dissolved in isopropyl alcohol under stirring,
2. methylene chloride and ethyl cellulose was added in above solution, followed by purified water,
3. drug loaded pellets prepared above were loaded into the bowl of Fluid Bed Equipment (FBE) and coated using polymer coating solution.
Cushion coating
1. PEG-6000, and hypromellose was dissolved in Purified water under stirring,

2. polymer coated pellets were loaded to RMG along with MCC, crospovidone,
3. polymer coated pellets were loaded into the bowl of Rapid mixer granulator (RMG) and granulated the pellets using PEG coating solution,
4. after granulation the pellets are wet milled, dried and sifted through ASTM # 12 mesh.
Blending and lubrication
1. colloidal silicon dioxide co-sifted with microcrystalline cellulose,
2. blend the PEG granulated pellets and extra granular colloidal silicon dioxide, crospovidone, microcrystalline cellulose in octagonal blend and
3. lubricated the blenedd granules with sodium stearyl fumarate.
Compression and film coating:
1. Lubricated granules were compressed into tablets and
2. Film coated the compressed tablets with Opadry White.

The tablets were prepared using the process similar to the procedure described for Example 1.
The dissolution profile of Metoprolol succinate extended release tablets prepared above was compared with the Reference standard Toprol XL(R) using USP II Apparatus. 500 mL pH 6.8 medium and 50 rpm.

The tablets prepared according to the present invention when stored at 40°C/75% RH & 25°C/60% RH condition were found to be stable. Given below table shows the stability data of tablets of present invention.

Blend Uniformity And Content Uniformity
Average blend uniformity and content uniformity of the tablets were determined. Average blend uniformity of each batch of the granulate was determined by taking 10 samples that represent the upper, middle and lower layer of each batch of the final blend (before tableting,) performing an HPLC assay to measure the amount of active ingredient in the samples, and comparing the amount of active ingredient in each sample to the labelled amount of active ingredient.
Content uniformity of the tablets was determined using 10 random tablets, by performing an HPLC assay to measure the amount of active ingredient in each tablet, and comparing the amount of active ingredient in each tablet to the labelled amount of active ingredient. Content uniformity of the batches tested ranged from 99.5% to 106.9%. RSD (relative standard deviation, expressed as a percentage of the mean) was lower than 2.0% for all of the batches of tablets, indicating that the uniformity of tablets was high despite the small amount of active ingredient in each tablet. As such, these results would pass the acceptance criteria set by the first stage of the USP content uniformity test.

We claim :
1. An oral extended tablet dosage form of'Metoprolol succinate, comprising :
a) an inert core comprising at least about 10 to 20% (w/w) of dosage form;
b) a drug layer comprising Metoprolol succinate, coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising at least one water insoluble polymer and one binder to form extended release pellets;
d) cushioning layer coated on the extended release pellets applied using high shear mixer and
e) at least one tablet excipient.

2. The extended release tablets of claim 1. wherein the inert core is selected from water insoluble such as silicon dioxide; water swellable such as microcrystalline cellulose spheres or water soluble such as lactose beads.
3. The extended release tablets of claim 1. wherein the water insoluble polymer is selected from ethyl cellulose, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, hydroxypropyl methyl acetate succinate, cellulose acetate, poly(melhacrylic acid, poly(methacrylic acid, ethyl acrylate) 1:1, poly(ethyl acrylate, methyl methacrylate) 2:1, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1 :2:0.2, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.1, methyl methacrylate) i: I, poly(methacrylic acid, methyl methacrylate) 1:2 or mixture thereof.
4. The water insoluble polymer of claim 4, wherein the water insoluble polymer is present in the range from about 5 to 15% w/w of the tablets.
5. The tablets of claim I. wherein the extended release polymeric layer comprises binder selected from hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methylcellulose. povidone or mixture thereof.

6. The extended release tablets of claim i, wherein drug layer and extended release coat are applied onto the inert core by spray coating in a conventional coating pan or fluidized bed processor or dip coating.
7. The extended release tablets of claim 1, wherein the cushioning layer is applied using high shear mixer granulator.
8. The extended release tablets of claim L wherein the cushioning layer comprises water soluble polymer selected from polyethylene glycol for example commercially marketed as Macrogol. such as macrogol 3350. macrogol 4000 or macrogol 6000; binder such as hydroxypropy!methyl cellulose, hydroxypropyl cellulose, povidone or mixture thereof.
9. The tablets of claim 1. wherein the extended release pellets are blended with one or more excipients such as diluents, disintegrants selected from microcrystalline cellulose, lactose, crospovidone, sodium starch glycolate. croscarmellose sodium or mixture thereof, before applying cushioning layer.
10. The Tablets of claim 1, wherein tablet excipient comprises diluents selected from lactose, microcrystalline cellulose, mannitol. starch, modified starch, Starlac®, or mixtures thereof, disintegrants such as microcrystalline cellulose, crospovidone, sodium starch glycolate; lubricants selected from magnesium stearate, stearic acid, sodium stearyl fumarate, glyceryl behenatc, talc, zinc stearate, silicon dioxide.
11. The extended release- tablets of claim 1. wherein the content uniformity of the tablets is between 95% and 115% and blend uniformity is between 95% and 105% and the relative standard deviation of the blend uniformity is less than 2%.
12. An oral extended release solid dosage form of Metoprolol succinate, comprising :
a) an inert core comprising at least about 1.0 to 20% (w/w) of dosage form;

b) a drug layer comprising Metoprolo! succinate, coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising at least one water insoluble polymer and one binder to form extended release pellets:
d) cushioning layer comprising 20 to 35 % w/w coated on the extended release pellets, applied using high shear mixer granulator and
e) at least one tablet excipient.
13. An oral extended tablets of Metoproiol succinate, comprising :
a) an inert core of macrocrystalline cellulose spheres comprising at least about 10 to
20% (\v/w) of dosage form;
b) a drug layer comprising Metoproiol succinate and a binder selected from
hydroxypropyl methyl cellulose; hydroxypropyl cellulose, methylcellulose or
povidone, coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising at least one water insoluble polymer
from about 5 to 15% w/w of the tablets and one binder to form extended release
pellets;
d") 20 to 35% w/w of the tablet dosage form a cushioning layer comprising polyethylene glycol and hypromellose, coated on the extended release pellets applied using high shear mixer granulator and e) at least one tablet excipient.
14. The extended release tablets of Metoproiol succinate: prepared by a process
which comprises the steps of:
a) applying a drug layer comprising Metoproiol succinate on inert core comprising at least about 10 to 20% (w/w) of dosage form to obtain drug loaded pellets using .fluid bed process..
b) applying an extended release polymer layer comprising at least one water insoluble polymer to form extended release pellets using fluid bed processor:
c) applying cushioning layer comprising polyethylene glycol and hypromellose on the extended release pellets using high shear mixer granulator and

d) blending the pellets obtained in step (c) with tableting excipients and
e) compressing the blend obtained .in step (d) to obtain extended release tablets.
1.5. An oral extended tablets of Metoprolol succinate., which comprises :
a) an inert core of microcrystalline cellulose spheres comprising at least about 1.0 to 20% (vv/w) of dosage form;
b) a drug layer comprising Metoprolol succinate and hydroxypropyl methyl cellulose, coated on the said inert core to obtain drug loaded pellets;
c) an extended release polymer layer comprising 5 to 15% w/w of ethylcellulose and hypromellose to form extended release pellets;
d) 20 to 35% w/w of the tablet dosage form a cushioning layer comprising
polyethylene glycol microcrystalline cellulose, crospovidone and hypromellose
coated on the extended release pellets applied using high shear mixer granulator and
e) tableting excipients comprising microcrystalline cellulose, crospovidone. colloidal
silicon dioxide and sodium stearyl fumarate.
16. The extended release tablets of Metoprolol succinate, prepared by a process which comprises the use of combination of fluid bed process / granulation and high shear mixer granulator.