DESC:FIELD OF THE INVENTION

The present invention related to a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition is prepared by direct compression method.

BACKGROUND OF THE INVENTION

Palbociclib is a selective inhibitor of CDK4 and CDK6 and is chemically described as 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2­
yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one.

Formula I

Palbociclib in the form of free base is approved in the form of capsules and tablets and marketed by Pfizer under the brand name IBRANCE®. The capsules and tablets are approved in the strengths of 75 mg, 100 mg and 125 mg and is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with:
• an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men; or
• fulvestrant in patients with disease progression following endocrine therapy.

WO2003062236 patent discloses palbociclib or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof. WO03062236 patent relates to substituted 2-amino pyridines that are potent inhibitors of cyclin-dependent kinase 4. The compounds of the invention are useful for the treatment of inflammation, and cell proliferative diseases such as cancer and restenosis.

WO2016193860 patent discloses a solid dosage form comprising palbociclib, a water-soluble acid and a pharmaceutically acceptable carrier. WO2016193860 patent discloses a solid dosage form comprises from about 10 wt% to about 35 wt% of palbociclib, from about 5 wt% to about 25 wt% of a water-soluble acid selected from the group consisting of succinic acid, malic acid and tartaric acid, and a pharmaceutically acceptable carrier and further disclose the granulation method where dry granulation method is preferred method of granulation.

WO2016070834 discloses a composition comprising palbociclib or a salt thereof and a pharmaceutically acceptable excipient as a carrier, wherein the salt is selected from the group consisting of hydrochloride and isethionate. Further WO2016070834 patent discloses composition comprising different percentages of palbociclib, diluent, disintegrant, lubricant, binder and surfactant.

WO2016030439 discloses a composition comprising different percentages of Palbociclib, filler, disintegrant, lubricant, glidant, and surfactant.

WO2016070833 discloses a composition comprising a solid dispersion prepared by palbociclib, a disintegrant, a diluent, a binder, a lubricant, a glidant.

WO2016156070 discloses a crystalline free base of palbociclib having specific surface area and its preparation method. Further WO2016156070 also discloses a pharmaceutical composition comprising an effective amount of palbociclib and a pH modifier which is a weak acid, preferably an organic acid.

WO2017036390 discloses a pharmaceutical composition containing a Palbociclib solid dispersion, comprising a solid dispersion formed by Palbociclib and an organic carrier and at least one pharmaceutical excipient, wherein Palbociclib is amorphous. The pharmaceutical composition of the present invention increases the dissolution rate of Palbociclib, and helps improve the bioavailability of medicine.

WO2017115315 discloses an amorphous solid dispersion of palbociclib with a pharmaceutically acceptable excipient.

WO2017130219 discloses composition comprising a stable amorphous solid dispersion of Palbociclib with one or more pharmaceutically acceptable carrier, optionally with one or more pharmaceutically acceptable excipients and process for the preparation of the composition.

WO2018191950 discloses a Palbociclib composition comprising Palbociclib co-milled with at least one hydrophilic excipient.

WO2021220295 patent discloses an immediate release tablet composition comprising palbociclib, water soluble acid and one or more pharmaceutically acceptable excipients where palbociclib and water soluble acid present in separate layers, which showed comparable/better dissolution with respect to the marketed tablet dosage forms of Palbociclib.

The above prior art references disclose different compositions comprising Palbociclib. However, there still exists a need for the development of formulations comprising Palbociclib. The present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients, wherein the said composition is prepared by direct compression method; and has comparable dissolution properties and stability equivalent to commercialized palbociclib tablet dosage form.

OBJECT OF THE INVENTION

The primary object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition is prepared by direct compression method.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose, wherein the weight ratio of palbociclib to microcrystalline cellulose from ranging about 1:2.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose; wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof; and wherein the said composition is prepared by direct compression method.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose; wherein the weight ratio of palbociclib to microcrystalline cellulose from ranging about 1:2; wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof; and wherein the said composition is prepared by direct compression method.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the water soluble acid is not selected from the group consisting of succinic acid, malic acid and tartaric acid.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the one or more pharmaceutical acceptable excipients is selected from one or more diluents, one or more disintegrants, one or more binders, one or more glidants, one or more lubricants or the mixtures thereof.

Another object of the present invention is to provide a process for preparation of stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said process for preparation is direct compression method.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein palbociclib is released more than 50% at 60 minutes when the said composition is subjected to the dissolution test using paddle method at a rotation of 50 rpm in 50 mM pH 6.5 phosphate buffer, 0.1 M NaCl and 500 ml of purified water.

Another object of the present invention is to provide a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition does not have more than 2% (w/w) of total impurity of palbociclib, after being stored at specific storage conditions.

SUMMARY OF THE INVENTION

The present invention related to a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition is prepared by direct compression method.

DETAILED DESCRIPTION

Unless otherwise indicated, terms in this specification are intended to have their ordinary meaning in the relevant art.

The present invention related to a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition is prepared by direct compression method.

The term “Palbociclib” used throughout the specification refers to not only their base per se, but also their other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof.

The term “pharmaceutically acceptable” means salt, carriers, excipients, and other formulation ingredients that are compatible with all other pharmaceutical ingredients of a composition and are not deleterious to an individual treated with composition.

The term “stable” as used throughout the specification, refers to a pharmaceutical composition in which the active pharmaceutical ingredients palbociclib is present in an amount of at least 90% of the original label specified amount for each such ingredient during specific storage conditions.

The term “specific storage conditions” as used throughout the specification, refers to the pharmaceutical composition of present invention stored for at least 1 month at 40°C/75% RH.

The term "premix" means a composition formed by the admixture of palbociclib or its pharmaceutically acceptable salt thereof and microcrystalline cellulose where the weight ratio of palbociclib to microcrystalline cellulose can be typically from ranging about 1:2 or any other suitable ratio.

In accordance with the present invention, the term “about” shall mean a variation up to 10% (plus or minus 10%) of the particular term.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose and wherein the weight ratio of palbociclib to microcrystalline cellulose from ranging about 1:2.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose; wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof; and wherein the said composition is prepared by direct compression method.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said palbociclib is present in a premix with microcrystalline cellulose, wherein the weight ratio of palbociclib to microcrystalline cellulose from ranging about 1:2; wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof; and wherein the said composition is prepared by direct compression method.

The water soluble acids can be selected from the group comprising of but not limited to fumaric acid, ascorbic acid, benzoic acid, tosylic acid, formic acid, lactic acid, acetic acid, citric acid, propionic acid, butyric acid, oxalic acid, uric acid, benzenesulfonic acid and the like or combinations thereof, more preferably ascorbic acid and citric acid. The water soluble acids can be present in a concentration of from about 8 % to about 25% by weight of the total weight of the composition.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the water soluble acid is not selected from the group consisting of succinic acid, malic acid and tartaric acid.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein one or more pharmaceutical acceptable excipients are selected from one or more diluents, one or more disintegrants, one or more binders, one or more glidants, one or more lubricants or the mixtures thereof.

The diluents can be selected from the group comprising of but not limited to mannitol, dibasic calcium phosphate anhydrous, microcrystalline cellulose, corn starch, sucrose or other sugar or sugar derivatives, low substituted HPC, pregelatinized starch or mixture thereof, more preferably microcrystalline cellulose. The diluents can be present in a concentration of from about 5% to about 30% by weight of the total weight of the composition.

The disintegrant can be selected from the group comprising of but not limited to croscarmellose sodium, crospovidone, sodium starch glycolate, starch, corn starch, pregelatinized starch or mixture thereof, more preferably crospovidone. The disintegrant can be present in a concentration of from about 1% to about 10% by weight of the total weight of the composition.

The binder can be selected from the group comprising of but not limited to pregelatinized starch, polyvinylpyrrolidone, povidone, copovidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, maize starch, microcrystalline cellulose or mixture thereof. The binder can be present in a concentration of from about 0.5% to about 10% by weight of the total weight of the composition.

The lubricant can be selected form the group comprising of agar, calcium stearate, ethyl oleate, ethyl laureate, glycerin, glyceryl palmitostearate, hydrogenated vegetable oil, magnesium oxide, magnesium stearate, sodium stearyl, sorbitol, stearic acid, talc, and zinc stearate or mixture thereof, more preferably magnesium stearate. The lubricant can be present in a concentration of from about 0.5% to about 4% by weight of the total weight of the composition.

The glidant can be selected from the group comprising of colloidal silicon dioxide, magnesium silicate, starch, talc, tribasic calcium phosphate, stearic acid, palmitic acid, polyethylene glycol, carnauba wax or mixtures thereof, more preferably colloidal silicon dioxide. The glidant can be present in a concentration of from about 0% to about 2% by weight of the total weight of the composition.

In one of the embodiments, the present invention provides a process for preparation of stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition is prepared by direct compression method.

The use of direct compression method may be preferred to granulation methods because it requires fewer unit operations, eliminates wetting and drying steps, and changes in dissolution profile are less likely to occur in tablets made by direct compression method.

In one of the embodiments, the present invention provides a process for preparation of stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients, comprising following steps:
1) Co-sift palbociclib premix with diluent, water soluble acid and disintegrant and mix in blender.
2) Co-sift glidant and lubricant, add to step-1 materials in a blender and mix.
3) Compress the step 2 blend using compression machine.
4) As an optional step, coating can be performed as follows: disperse coating material in purified water under mechanical stirrer. Load the compressed tablets in auto-coater and start coating using aqueous dispersion of coating material, until desired weight gain achieved.

In one of the embodiment, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the palbociclib is released more than 50% at 60 minutes when the said composition is subjected to the dissolution test using paddle method at a rotation of 50 rpm in 50 mM pH 6.5 phosphate buffer, 0.1 M NaCl and 500 ml of purified water.

In one of the embodiments, the present invention provides a stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition does not have more than 2% (w/w) of total impurity of palbociclib, after being stored at specific storage conditions.

The present invention has been described by way of example only. It is to be recognized that modifications falling within the scope and spirit of the claims, which would be obvious to a person skilled in the art based upon the disclosure herein, are also considered to be included within the scope of this invention. The scope of the invention is in no manner limited by the disclosed example.

Example 1

Sr. No Ingredients % w/w
1 Palbociclib premix 45-75
2 Diluent 5-30
3 Water soluble acid 8-25
4 Disintegrant 1-10
5 Glidant 0-2
6 Lubricant 0.5-4
9 Film Coating material Qs
Weight of coated tablet 100

Manufacturing process:
1. Co-sift palbociclib premix with diluent, water soluble acid and disintegrant and mix in blender.
2. Co-sift glidant and lubricant, add to step-1 materials in a blender and mix.
3. Compress the step 2 blend using compression machine.
4. Disperse coating material in purified water under mechanical stirrer. Load the compressed tablets in auto-coater and start coating using aqueous dispersion of coating material, until desired weight gain achieved.

Example 2

Sr. No Ingredients 75 mg 100 mg 125 mg
1 Palbociclib premix 225.02 300.03 375.03
2 Microcrystalline Cellulose 18.75-112.50 25.00-150.00 31.25-187.50
3 Ascorbic acid 30.00-93.75 40.00-125.00 50.00-156.25
4 Crospovidone 11.25-30.00 15.00-40.00 18.75-50.00
5 Colloidal Silicon Dioxide 0.00- 7.50 0.00-10.00 0.00-12.50
6 Magnesium Stearate 1.88-15.00 2.50-20.00 3.13-25.00
Total weight of tablet 375.00 500.00 625.00
Film Coating material
7 Opadry Purple 12.00 - 20.00
8 Opadry Green - 16.00 -
Weight of coated tablet 387.00 516.00 645.00

Manufacturing process:
1. Co-Sift Palbociclib Premix, Microcrystalline Cellulose, Ascorbic acid and crospovidone through #40 ASTM sieve and mix for 10 minutes in blender.
2. Co-sift Colloidal Silicon Dioxide and Magnesium stearate through #40 ASTM sieve, add to step-1 materials in a blender and mix for 5 minutes.
3. Compress the step 2 blend using compression machine.
4. Disperse coating material in purified water for 45 minutes under mechanical stirrer. Load the compressed tablets in Auto-coater and start coating using aqueous dispersion of coating material, until desired weight gain achieved.

Example 3

Sr. No Ingredients 75 mg 100 mg 125 mg
1 Palbociclib premix 225.02 300.03 375.03
2 Microcrystalline Cellulose 18.75-112.50 25.00-150.00 31.25-187.50
3 Citric acid 30.00-93.75 40.00-125.00 50.00-156.25
4 Crospovidone 11.25-30.00 15.00-40.00 18.75-50.00
5 Colloidal Silicon Dioxide 0.00- 7.50 0.00-10.00 0.00-12.50
6 Magnesium Stearate 1.88-15.00 2.50-20.00 3.13-25.00
Total weight of tablet 375.00 500.00 625.00
Film Coating material
7 Opadry Purple 12.00 - 20.00
8 Opadry Green - 16.00 -
Weight of coated tablet 387.00 516.00 645.00

Manufacturing process:
1. Co-sift palbociclib Premix, microcrystalline cellulose, citric acid and crospovidone through #40 ASTM sieve and mix for 10 minutes in blender.
2. Co-sift colloidal silicon dioxide and magnesium stearate through #40 ASTM sieve, add to step-1 materials in a blender and mix for 5 minutes.
3. Compress the step 2 blend using compression machine.
4. Disperse coating material in purified water for 45 minutes under mechanical stirrer. Load the compressed tablets in Auto-coater and start coating using aqueous dispersion of coating material, until desired weight gain achieved.

DISSOLUTION STUDY
The composition of examples 2 and 3 were tested for dissolution study as per USP dissolution apparatus 2 (paddle) at 50 rpm using 50 mM pH 6.5 phosphate buffer, 0.1 M NaCl and 500 ml of purified water, and gave the following results as Table 1.

Table 1:

Sr. No. Time point Innovator-125 mg strength) Without Acid 125 mg With Ascorbic Acid 125 mg With Citric Acid 125 mg
1 15 34(23-40) 10(9-11) 45(42-46) 52(51-53)
2 30 50(49-51) 12(11-13) 50(48-51) 54(54-55)
3 45 51(51-52) 13(12-13) 50(48-51) 54(54-55)
4 60 51(51-52) 14(13-14) 52(50-52) 56(55-57)

The above dissolution study shows the release of palbociclib is more than 50% at 60 minutes and is similar to the commercially available product.

STABILITY STUDY
Table 2: Stability data of palbociclib tablet 125 mg under 1 month time interval at condition of 40°C / 75 % RH in open exposure.

Related substances Without Acid - 125 mg With Succinic Acid -125 mg With Ascorbic Acid -125 mg With Citric Acid -125 mg
Single max unknown impurity 0.072
(RRT 3.47) 0.320 (RRT 3.47) 0.447 (RRT 3.45) 0.139 (RRT 2.32)
Total Impurities 0.203 1.358 0.815 0.495

Table 3: Stability data of palbociclib tablet 125 mg under 1 month time interval at condition of 40°C / 75 % RH in Alu- Alu Blister.

Related substances With Succinic acid -125 mg With Ascorbic Acid -125 mg With Citric acid -125 mg
Single max unknown impurity 0.067
(RRT 0.84) 0.077
(RRT 0.77) 0.041
(RRT 0.84)
Total Impurities 0.232 0.310 0.125

The above data shows a total impurity not more than 2% in the formulation, indicative of stability of palbociclib in the drug product. ,CLAIMS:We Claims:

1. A stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients; wherein the said composition is prepared by direct compression method.

2. The stable pharmaceutical composition of palbociclib according to claims 1, wherein the said palbociclib is present in a premix with microcrystalline cellulose.

3. The stable pharmaceutical composition of palbociclib according to claims 1, wherein the said palbociclib is present in a premix with microcrystalline cellulose, wherein the weight ratio of palbociclib to microcrystalline cellulose from ranging about 1:2.

4. The stable pharmaceutical composition of palbociclib according to claims 1, wherein the water soluble acid is selected from ascorbic acid, fumaric acid, adipic acid, sorbic acid, tosylic acid, citric acid and combinations thereof.

5. The stable pharmaceutical composition of palbociclib according to claims 1, wherein the water soluble acid is not selected from the group consisting of succinic acid, malic acid and tartaric acid.

6. The stable pharmaceutical composition of palbociclib according to claims 1, wherein the one or more pharmaceutical acceptable excipients is selected from one or more diluents, one or more disintegrants, one or more binders, one or more glidants, one or more lubricants or the mixtures thereof.

7. A process for preparation of stable pharmaceutical composition of palbociclib comprising palbociclib or its pharmaceutically acceptable salt thereof, a water soluble acid and one or more pharmaceutical acceptable excipients, comprising following steps:
1. Co-sift palbociclib premix with diluent, water soluble acid and disintegrant and mix in blender.
2. Co-sift glidant and lubricant, add to step-1 materials in a blender and mix.
3. Compress the step 2 blend using compression machine.
4. Optionally, coat the compressed tablets using coating solution.

8. The stable pharmaceutical composition of palbociclib according to claims 1, wherein palbociclib is released more than 50% at 60 minutes when the said composition is subjected to the dissolution test using paddle method at a rotation of 50 rpm in 50 mM pH 6.5 phosphate buffer, 0.1 M NaCl and 500 ml of purified water.

9. The stable pharmaceutical composition of palbociclib according to claims 1, wherein the said composition does not have more than 2% (w/w) of total impurity of palbociclib, after being stored at 40°C/75% RH for at least 1 month.