FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
PATENTS RULES, 2006
COMPLETE SPECIFICATION
(SECTION 10; RULE 13)
"STABLE PHARMACEUTICAL COMPOSITIONS OF EZETIMIBE IN COMBINATION WITH HMG COA REDUCTASE INHIBITORS"
V-ENSURE PHARMA TECHNOLOGIES PRIVATE LIMITED, A COMPANY
INCORPORATED UNDER THE COMPANIES ACT, 1956, HAVING ITS CORPORATE.
OFFICE AT MUMBAI, MAHARASHTRA, INDIA
THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED

FIELD OF THE INVENTION
The present invention relates to a stable pharmaceutical composition of Ezetimibe with the combination of HMG CoA reductase inhibitors with one or more pharmaceutically acceptable excipients and at least one organic acidifier wherein particularly citric acid and ascorbic acid are omitted.
BACK GROUND OF THE INVENTION
Ezetimibe, a selective inhibitor of intestinal cholesterol and related phytosterol absorption. The chemical name of ezetimibe is l-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone.
Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is:

Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick Cl-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. In a 2-week clinical study in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production
HMG-CoA reductase (or 3-hydroxy-3-methyl-glutaryl-CoA reductase or HMGCR) is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels

have been associated with cardiovascular diseases (CVD), and statins are therefore used in the prevention of these diseases
Many statins are approved for human consumption like Fluvastatin, Lovastatin, Simvastatin, Pravastatin, Simvastatin, Atorvastatin, Rosuvastatin and Pitavastatin.
As Ezetimibe and HMG CoA reductase inhibitors work synergistically to lower the cholesterol level, Ezetimibe in combination with Simvastatin is approved with the various brand names worldwide like Vytorin etc.
Simvastatin, an inactive lactone, is hydrolyzed to the corresponding β -hydroxyacid form, which is an inhibitor of HMGCoA reductase. Simvastatin is butanoic acid, 2,2-dimethyl-,l,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-l-naphthalenyl ester, [lS-[lα,3α,7β,8P(2S*,4S*),-8aβ]]. The empirical formula of simvastatin is C25H38O5 and its molecular weight is 418.57.
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water and freely soluble in chloroform, methanol and ethanol. Its structural formula is:

US7229982 ('982 patent) discloses the compositions which are stabilized by 0.01% to 2 % of Butyl hydroxyl Anisol and 0.1% to 1.25 % citric acid. US7718643 ('643 patent) discloses the compositions which are stabilized by 0.005 % to 10 % of ascorbic acid.
EP1901736 ('736 patent) discloses stabilization of Ezetimibe and simvastatin compositions without stabilizer. As per the disclosure, dosage form needs to be preserved in the reduced oxygen atmosphere which is costly and may not be suitable for container pack such as HDPE packs

Accordingly, there is a continuing need in the art for an improved pharmaceutical formulation of HMG CoA reductase inhibitors, one or more pharmaceutically acceptable excipients and anti-oxidants essentially the present invention to provide a pharmaceutical composition comprising simvastatin and ezetimibe and anorganic acidifiers wherein particularly citric acid and ascorbic acid are omitted.
The present invention meets the unfulfilled needs of the pharmaceutical industry by providing an improved pharmaceutical formulation of HMG CoA reductase inhibitors, one or more pharmaceutically acceptable excipients and anti-oxidants essentially the present invention to provide a pharmaceutical composition comprising simvastatin and ezetimibe and an organic acidifiers wherein particularly citric acid and ascorbic acid are omitted.
The invention also provides the stable composition of Ezetimibe with the combination of HMG CoA reductase inhibitors with one or more pharmaceutically acceptable excipients and at least one anti-oxidant and essentially pharmaceutical composition does not contain an organic acidifiers such as citric acid and ascorbic acid that overcomes the problems of the prior art.
The problem to be solved by the present invention was therefore to provide an improved stable pharmaceutically formulation method for the production of a pharmaceutical containing Ezetimibe with the combination of HMG CoA reductase inhibitor, in which the aforementioned dis-advantages and in particular the trace quantities of metals, and exposure to light, cause discoloration and loss of activity are essentially avoided or overcome. Present invention also avoid the expensive preservation of dosage form under the reduced oxygen atmosphere which is costly and may not be suitable for container pack such as HDPE packs
OBJECT OF THE INVENTION
It is an object of the present invention to provide a stable pharmaceutical composition of Ezetimibe with the combination of HMG CoA reductase inhibitors with one or more pharmaceutically acceptable excipients and at least one organic acidifier.
It is another object of the present invention to provide a stable pharmaceutical composition comprising ezetimibe and simvastatin and an organic acidifiers wherein particularly citric acid and ascorbic acid are omitted.

Accordingly, it is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.
SUMMARY OF THE INVENTION
In an embodiment of the present inventon, stable pharmaceutical composition of Ezetimibe with the combination of HMG CoA reductase inhibitors with one or more pharmaceutically acceptable excipients and at least one organic acidifier.
In an another embodiment of the present inventon, a stable pharmaceutical composition comprising simvastatin and ezetimibe and an organic acidifiers wherein particularly citric acid and ascorbic acid are omitted.
In addition to the pharmaceutical formulation, another important physical property is stability. The present invention also provides Pharmaceutical formulations with improved stability over prior pharmaceutical formulations.
The specific dose administered according to the present invention is determined by the particular circumstances surrounding the case including, for example, the route of administration, the dosage form, the condition of the patient, and the pathological condition being treated. A typical daily dose contains a dosage level of about 1 to about 10 mg/day of Ezetimibe, particularly about 10 mg and the daily doses generally are about 1 to about 80 mg/day of Simvastatin, particularly about 5 mg or about 80 mg tablets or capsules, administered once per day. The most preferred dosage form is a tablet.
According to another preferred embodiment, the simvastatin and ezetimibe are used for the preparation of a medicament for the prevention and/or treatment of atherosclerosis and related conditions or for the reduction of plasma cholesterol levels. Atherosclerosis is a disease characterized by a progressive narrowing and hardening of the arteries over time. The occurrence of atherosclerosis is preliminary known to take place to certain degree with aging, but other risk factors that accelerate this process have been identified, such as high plasma cholesterol, high blood pressure, smoking, diabetes and genetic disposition for atherosclerotic disease
The invention may be summarized as given below:

A. A pharmaceutical composition comprising simvastatin and ezetimibe and an organic
acidifiers wherein particularly citric acid and ascorbic acid are omitted.
B. The pharmaceutical composition as in step A above, wherein the acidifier is selected
from the acetic acid, lactic acid, maleic acid, fumaric acid, succinic acid, tartaric acid
pyruvic acid and phosphoric acid and combination thereof.
C. The pharmaceutical composition as in step A above, wherein the diluent is selected
from the group consisting of microcrystalline cellulose, mannitol, dextrates, dextrins,
dextrose, fructose, lactose, lactitol, maltitol, maltodextrins, maltose and the like and
mixtures thereof.
D. The pharmaceutical composition as in step A above, wherein the disintegrants is
selected from the group consisting of carboxymethylcellulose calcium,
carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium,
crospovidone, magnesium aluminum silicate, methylcellulose, microcrystalline
cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium
alginate, sodium starch glycolate, and starch and the like or mixtures thereof.
E. The pharmaceutical composition as in step A above, wherein the lubricant is selected
from the group consisting of talc, magnesium stearate, calcium stearate, stearic acid,
SSF, hydrogenated vegetable oils, polyethylene glycol and the like and mixtures
thereof.
F. The pharmaceutical composition as in step A above, wherein the typical glidants is
selected from the group consisting of colloidal silicon dioxide, talc and the like and
mixtures thereof.
G. The pharmaceutical composition as in step A above, wherein the wicking agent is
selected from the group consisting of colloidal silicon dioxide, kaolin, titanium
dioxide, fumed silicon dioxide, m-pyrol, vinylpyrrolidone polymers such as povidone,

or crosslinked polyvinylpyrrolidone such as crospovidone; cellulose and cellulose derivatives such as microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropyl cellulose, carboxyalicyl celluloses and their alkali salts; sodium starch glycolate, starch and starch derivatives, ion-exchange resins and the like and mixtures thereof.
H. The pharmaceutical composition as in step A above, wherein the solubilizer is selected from the group consisting of polysorbates, polaxomers and and other non-inoic and anionic surfactants and the like and antioxidants known in the art such as butylated hydroxyl anisol and the like mixtures thereof.
I. The pharmaceutical composition as in step A above, wherein the binders is selected from the group consisting of starch, gelatin, dextrin, maltodextrin, natural and synthetic gums like acacia, alginic acid, sodium alginate, guar gum, extract of fish moss, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, veegum, arabogalactan and the like and mixtures thereof.
J. The pharmaceutical composition as in step A above, wherein 1 to about 10 mg/day of Ezetimibe and 1 to about 80 mg/day of Simvastatin is present per tablet.
K. The pharmaceutical composition as in step A above, which is in a solid dosage form selected from the group consisting of tablets, capsules, sachets, lozenges, powders, pills and granules.
L. The pharmaceutical composition as in step A above, additionally containing an excipient selected from the group consisting diluents, binding agents, disintegrants, lubricants, sweeteners, glidants, flavourings and colouring agents.

DESCRIPTION OF THE INVENTION
Before the present formulations and methods are described, it is to be understood that this invention is not limited to particular compounds, formulas or steps described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of . describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the invention.
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 this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described. AH publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.
It must be noted that as used herein and in the appended claims, the singular forms "a", "and", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a compound" includes a plurality of such compounds and reference to "the step" includes reference to one or more step and equivalents thereof known to those skilled in the art, and so forth.
The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
The present invention to provide a stable pharmaceutical composition of Ezetimibe with the combination of HMG CoA reductase inhibitors with one or more pharmaceutically acceptable excipients and at least one organic acidifier.
The present invention to also provide a stable pharmaceutical composition comprising ezetimibe and simvastatin and an organic acidifiers wherein particularly citric acid and ascorbic acid are omitted.
The term " pharmaceutically acceptable anti-oxidants" means excipients listed in hand book of excipeints by Ray C Rowe, Paul J Sheskey and Paul J Weller. The preferred anti-oxidants are propyl gallate, , tocopherols Butyl hydroxyl tolune, citric acid, fumaric aid, malic acid, propionic acid, sodium ascorbate, sodium meta bisulphate and its related compounts, tartaric acid.
The term "pharmaceutically effective amount of anti-oxidant" means the concentration ranging from 0.001 % to 1 %
The term "pharmaceutically acceptable excipients" include those which function in a dosage form, for example, as a disintegrant, lubricant, glidant, fillers or diluents, wicking agents, carrier, colorant or coating material
In preferred embodiments the composition of the present invention is formed into tablets. The fillers or diluents that may be used in the stable oral pharmaceutical composition of the present invention include microcrystalline cellulose, mannitol, dextrates, dextrins, dextrose, fructose, lactose, lactitol, maltitol, maltodextrins, maltose and the like and mixtures thereof. Apreferred filler is microcrystalline cellulose or lactose or a combination thereof. The diluents or fillers may be used in amounts ranging from about 0.1 to about 80% w/w. It is preferred that the fillers are used in amounts ranging from about 1 to about 70% w/w of the composition.
The disintegrants that may be used in pharmaceutical composition of the present invention include carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate,

methylcellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate, and starch and the like or mixtures thereof. The disintegrants may be used in amounts ranging from about 0.1 to about 50% w/w. It is preferred that the fillers are used in amounts ranging from about 1 to about 20% w/w of the composition.
A pharmaceutical composition comprising simvastatin and ezetimibe and an organic acidifiers wherein particularly citric acid and ascorbic acid are omitted. The preferred acidifier compounds are the organic acids such as citric acid, acetic acid, lactic acid, maleic acid, fumaric acid, or succinic acid and combinations of organic acids such as maleic acid, fumaric acid, ascorbic acid tartaric acid and pyruvic acid. The inorganic acid, phosphoric acid, may also be used. Several of these acids also confer antimicrobial potential (e.g., acetic and lactic acids). Some also serve as chelating agents, which may be important to delivery of minerals and antioxidant properties (e.g., citric acid and succinic acid).
The lubricants used in the present invention may be selected from the group consisting of talc, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oils, polyethylene glycol and the like and mixtures thereof. Generally the amount of the lubricants used in the present invention may vary from about 0.001 to about 5 % w/w of the composition.
The typical glidants that may be included in the present invention include colloidal silicon dioxide, talc and the like. The amounts of glidants used in the present invention may vary from about 0.1 to about 5% w/w of the cdmposition.
Examples of wicking agents that may be used in the present invention include colloidal silicon dioxide, kaolin, titanium dioxide, fumed silicon dioxide, m-pyrol, vinylpyrrolidone polymers such as povidone, or crosslinked polyvinylpyrrolidone such as crospovidone; cellulose and cellulose derivatives such as microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropyl cellulose, carboxyalicyl celluloses and their alkali salts; sodium starch glycolate, starch and starch derivatives, ion-exchange resins and the like and mixtures thereof.

The composition of the present invention may also use solubilizers known in the art such as polysorbate 80 and the like and antioxidants known in the art such as butylated hydroxyl anisol and the like.
The binders used in the present invention may be selected from the group comprising of starch, gelatin, dextrin, maltodextrin, natural and synthetic gums like acacia, alginic acid, sodium alginate, guar gum, extract of fish moss, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, veegum, arabogalactan and the like and mixtures thereof.
The term "pharmaceutical composition" as used herein includes solid oral dosage forms such as pellets, beads, granules and the like, which may be encapsulated or compressed into tablets. The pellets, beads, granules in turn may be prepared by conventional methods known to a person skilled in the art. The compressed tablets may optionally be coated with film-coat.
The pharmaceutical compositions of the present invention, maybe prepared by the conventional processes such as wet granulation, dry granulation or direct compression or by various pellatization techniques.
The present invention is illustrated by the following examples without limiting it thereto.

EXAMPLES Example 1
Ezetimibe 10 mg
Simvastatin 5 mg to 80 mg
Microcrystalline cellulose 10 to 200 mg
Lactose 20 to 600 mg
HPMC 1 to 50 mg
Croscarmellose sodium 1 to 50 mg
Citric acid 0.1 to 20 mg
Magnesium stearate 1 to 20 mg
Example 2
Ezetimibe 10 mg
Simvastatin 5 mg to 80 mg
Microcrystalline cellulose 10 to 200 mg
Lactose 20 to 600 mg
HPMC 1 to 50 mg
Croscarmellose sodium 1 to 50 mg
Sodium metabisuphate 0.1 mg to 2 mg
Citric acid 0.1 to 20 mg
Magnesium stearate 1 to 20 mg

Example 3
Ezetimibe 10 mg
Simvastatin 5 mg to 80 mg
Microcrystalline cellulose 10 to 200 mg
Lactose 20 to 600 mg
HPMC 1to 50 mg
Croscarmellose sodium 1 to 50 mg
Sodium sulphate 0.1 mg to 2 mg
Citric acid 0.1 to 20 mg
Magnesium stearate 1 to 20 mg
Example 4
Ezetimibe 10 mg
Simvastatin 5 mg t0 80 mg
Microcrystalline cellulose 10 to 200 mg
Lactose 20 to 600 mg
HPMC 1 to 50 mg
Croscarmellose sodium 1 to 50 mg
Butyl hydroxyl tolune 0-1 mg to 2 mg
Citric acid 0.1 to 20 mg
Magnesium stearate 1 to 20 mg
Examples
Ezetimibe 10mg

Simvastatin 5 mg to 80 mg
Microcrystalline cellulose 10 to 200 mg
Lactose 20 to 600 mg
HPMC 1 to 50 mg
Croscarmellose sodium 1 to 50 mg
Alpha tocopherol 0.1 mg to 5 mg
Citric acid 0.1 to 20 mg
Magnesium stearate 1 to 20 mg

Example 6
Ezetimibe 10 mg
Simvastatin 5 mg to 80 mg
Microcrystalline cellulose 10 to 200 mg
Lactose 20 to 600 mg
HPMC 1 to 50 mg
Croscarmellose sodium 1 to 50 mg
Sodium ascorbate 0.1 mg to 30 mg
Citric acid 0.1 to 20 mg
Magnesium stearate 1 to 20 mg
Example 7
Product: Ezetimibe/Simvastatin Tablets 10/80 mg & 10/10 mg Formula:

Sr. No. Ingredient 10/80 mg 10/10 mg

mg/tab mg/tab
1 Ezetimibe 10.000 10.000
2 Simvastatin 80.000 10.000
3 Lactose Monohydrate 535.960 58.240
4 Microcrystalline Cellulose 120.000 15.000
5 Croscarmellose sodium 24.000 3.000
6 Hypromellose 16.000 2.000
7 Maleic acid 2.000 0.250
8 Propyl gallate 0.040 0.010
9 Magnesium Stearate 12.000 1.500
10 Purified water qs qs
11 Ethanol qs qs
Total weight of tablet 800.000 100.000

STABILITY DATA (Related Substances):
Impurity 40°C/75%RH

Initial 3M
Ezetimibe-A 0.07 ND
Ezetimibe-B 0.01 0.02
Ezetimibe-C 0.01 0.13
Ezetimibe-D 0.04 ND
Simvastatin -A 0.14 0.28
Simvastatin-B 0.04 0.07
Simvastatin-C 0.06 0.14
Simvastatin-D 0.28 0.16
Lovastatin & Epilovastatin 0.25 0.34
Hi-Unknown -Imp 0.09 0.09
Total Imp. (Excluding Lovastatin & Epilovastatin) 0.84 0.98
Although the invention has been described in terms of particular embodiments and applications, one of ordinary skill in the art, in light of this teaching, can generate additional embodiments and modifications without departing from the spirit of or exceeding the scope of the claimed invention. It should be emphasized that the above-described embodiments of the present invention, particularly any "preferred" embodiments, are merely possible examples of the invention of implementations, merely set forth for a clear understanding of the principles of the invention. Accordingly, it is to be understood that the drawings and descriptions herein are proffered by way of example to facilitate comprehension of the invention and should not be construed to limit the scope thereof.

We Claim:
1. A pharmaceutical composition comprising simvastatin and ezetimibe and an organic acidifiers wherein particularly citric acid and ascorbic acid are omitted.
2. The pharmaceutical composition according to claim 1, wherein the acidifier is selected from the acetic acid, lactic acid, maleic acid, fumaric acid, succinic acid, tartaric acid pyruvic acid and phosphoric acid and combination thereof.
3. The pharmaceutical composition according to claim 1, wherein the diluent is selected from the group consisting of microcrystalline cellulose, mannitol, dextrates, dextrins, dextrose, fructose, lactose, lactitol, maltitol, maltodextrins, maltose and the like and
mixtures thereof.
4. The pharmaceutical composition according to claim 1, wherein the disintegrants is selected from the group consisting of carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methylcellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate, and starch and the like or mixtures thereof.
5. The pharmaceutical composition according to claim 2, wherein the lubricant is selected from the group consisting of talc, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oils, polyethylene glycol and the like and mixtures thereof.

6. The pharmaceutical composition according to claim 1, wherein the typical glidants is selected from the group consisting of colloidal silicon dioxide, talc and the like and mixtures thereof.
7. The pharmaceutical composition according to claim 1, wherein the wicking agent is selected from the group consisting of colloidal silicon dioxide, kaolin, titanium dioxide, fumed silicon dioxide, m-pyrol, vinylpyrrolidone polymers such as povidone, or crosslinked polyvinylpyrrolidone such as crospovidone; cellulose and cellulose derivatives such as microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropyl cellulose, carboxyalicyl celluloses and their alkali salts; sodium starch glycolate, starch and starch derivatives, ion-exchange resins and the like and mixtures thereof.
8. The pharmaceutical composition according to claim 1, wherein the solubilizer is selected from the group consisting of polysorbate 80 and the like and antioxidants known in the art such as butylated hydroxyl anisol and the like mixtures thereof.
9. The pharmaceutical composition according to claim 1, wherein the binders is selected from the group consisting of starch, gelatin, dextrin, maltodextrin, natural and synthetic gums like acacia, alginic acid, sodium alginate, guar gum, extract of fish moss, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, veegum, arabogalactan and the like and mixtures thereof.
10. The pharmaceutical composition according to claim 1, wherein 1 to about 10 mg/day of Ezetimibe and 1 to about 80 mg/day of Simvastatin is present per tablet.

11. The pharmaceutical composition according to claim 1, which is in a solid dosage form selected from the group consisting of tablets, capsules, sachets, lozenges, powders, pills and granules.
12, The pharmaceutical composition according to claim 1, additionally containing an excipient selected from the group consisting diluents, binding agents, disintegrants, lubricants, sweeteners, glidants, flavourings and colouring agents.