DESC:“PHARMACEUTICAL COMPOSITIONS OF IPRAGLIFLOZIN”

FIELD OF INVENTION:
The present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, processes for the preparation of the pharmaceutical composition.

BACKGROUND OF INVENTION:
Glucose cotransporters (SLGTs) are a class of membrane proteins capable of transporting glucose into cells. SLGT has two isoforms, SLGT1 and SLGT2, which are distributed in the small intestinal mucosa and renal tubules, respectively. SLGT2 plays a critical role in proximal tubular glucose reabsorption.

Ipragliflozin is a SLGT2 inhibitor of the class of gliflozin, which selectively reduces the glucose concentration in the renal tubules by preventing the glucose in the renal tubules from being reabsorbed into the blood, but excreted in the urine. The chemical name of Ipragliflozin is (1S)-1,5-anhydro-1-{3-[(1-benzothiophen-2-yl) methyl]-4-fluorophenyl}-D-glucitol, the structure of the co-crystal formed by Ipragliflozin and L-proline is shown in formula (I).

The commercially available formulations of Ipragliflozin L-Proline contain the L-Proline solvate of Ipragliflozin as the active ingredient. The drug substance is crystalline in nature. In contrast, Ipragliflozin base is present in amorphous form.
PCT Publication No. WO2004080990A, WO 2007/114475A discloses C-glycoside derivatives and salts thereof.
PCT Publication No WO 2005/012326A discloses novel compounds having inhibitory activity against sodium-dependant transporter.
PCT Publication No. WO 2007/114475A discloses Cocrystal of c-glycoside derivative and 1-proline
US Pat. No. US8202984 discloses Glucopyranoside compound.
EP Pat. No. EP 3256482A1 discloses process for the preparation of SGLT inhibitor compounds.
PCT Publication No. WO2005012326 A1 discloses Novel compounds having inhibitory activity against sodium-dependant transporter.
China Pat. No. CN101443328 B discloses Cocrystal of C-glycoside derivative and L-proline.
Chinese patent CN 104382859 A dissolves or disperses SLGT2 inhibitor, crystal inhibitor and filler in a certain amount of water-containing organic solvent, and adopts the method of spray drying to prepare particles comprising SLGT2 inhibitor, crystal inhibitor and filler, and uses It can be further prepared into tablets, capsules, granules and other preparations; the preparation method solves the problem of low dissolution and bioavailability caused by poor water solubility of the SLGT2 inhibitor.
Chinese patent CN 102596206B discloses a solid pharmaceutical composition, characterized in that it comprises (1S)-1,5-anhydro-1-{3-[(1-benzothiophen-2-yl) methyl]-4 -fluorophenyl}-D-glucitol and L-proline co-crystals and crystalline cellulose.
The Ipragliflozin base is hygroscopic in nature. It absorbs moisture and forms sticky lumps which are difficult to process and handle, and which may ultimately lead to content uniformity issues in the dosage form. The low solubility and stability of Ipragliflozin base as compared to its solvates may lead to poor bioavailability of the drug.
Therefore, there exists a need to provide a stable form of Ipragliflozin base that is readily bioavailable and can be further processed to form stable compositions.
The inventors of the present invention have found that a solid dispersion of Ipragliflozin is more stable, has superior solubility, and has better processing abilities. Further, the solid dispersion can be conveniently formulated into various dosage forms.

SUMMARY OF INVENTION:
The Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients and processes for the preparation of the pharmaceutical composition.
The Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable excipients, where in the composition comprising a solid dispersion of Ipragliflozin and one or more pharmaceutically acceptable excipients.
The Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in the pharmaceutical composition is oral solid dosage form.
The Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients and formulations is prepared into powders, granules and tablets, methods for manufacturing and processing the powders, granules and tablets.
The Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable excipients, wherein the Ipragliflozin having 5-70% w/w of the composition.
The Present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in the particle size of Ipragliflozin is less than 250 microns, preferably less than 100 microns, more preferably less than 50 microns.
The Present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in Ipragliflozin is in the form of crystalline of amorphous form.
OBJECT OF INVENTION:
The primary objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients and processes for the preparation of the pharmaceutical composition.
Another objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. Where in the composition comprising a solid dispersion of Ipragliflozin and one or more pharmaceutically acceptable excipients.
Another objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in the composition comprising a solid dispersion of Ipragliflozin and a carrier, wherein the Ipragliflozin is dispersed or dissolved in the carrier.
Another objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in the pharmaceutical composition is oral solid dosage form.
Another objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients and formulations is prepared into powders, granules and tablets, methods for manufacturing and processing the powders, granules and tablets.
Another objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. wherein the Ipragliflozin having 5-70% w/w of the composition.
Another objective of the present invention relates to a process for the preparation of Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients having comparable dissolution properties, content uniformity, stability and equivalent bioavailability w.r.t commercialized Ipragliflozin dosage form.
Another objective of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients like diluent, binder, glidant, lubricant, solubilizer, antacid, disintegrant and colorant.
Another objective of the present invention is to provide a method for treatment of a diabetes by administering an immediate release pharmaceutical formulation comprising Ipragliflozin and its pharmaceutically acceptable salts.
Another objective of the present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in the particle size of Ipragliflozin is less than 250 microns, preferably less than 100 microns, more preferably less than 50 microns.
Another objective of the present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in Ipragliflozin is in the form of crystalline of amorphous form.
DETAILED DESCRIPTION OF INVENTION:
The Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients and processes for the preparation of the pharmaceutical composition.
Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. Where in the composition comprising a solid dispersion of Ipragliflozin and one or more pharmaceutically acceptable excipients.
Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in the composition comprising a solid dispersion of Ipragliflozin and a carrier, wherein the Ipragliflozin is dispersed or dissolved in the carrier.
Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in the pharmaceutical composition is oral solid dosage form.
Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients. where in formulations is prepared into powders, granules and tablets, methods for manufacturing and processing the powders, granules and tablets.
Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients and one or more pharmaceutically acceptable excipients, wherein the Ipragliflozin having 5-70% w/w of the composition.
Present invention relates to a process for the preparation of Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients having comparable dissolution properties, content uniformity, stability and equivalent bioavailability w.r.t commercialized Ipragliflozin dosage form.
Present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable excipients like diluent, binder, glidant, lubricant, solubilizer, antacid, disintegrant and colorant.
Present invention is to provide a method for treatment of a diabetes by administering an immediate release pharmaceutical formulation comprising Ipragliflozin and its pharmaceutically acceptable salts.
Present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in the particle size of Ipragliflozin is less than 250 microns, preferably less than 100 microns, more preferably less than 50 microns.
Present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in Ipragliflozin is in the form of crystalline of amorphous form.
The term "composition" or "formulation" or "dosage form" has been employed interchangeably for the purpose of the present invention and mean that it is a pharmaceutical composition which is suitable for administration to a patient or subject.
The subject can be an animal, preferably a mammal, more preferably a human. For the purpose of the present invention terms "immediate release" or "sustained release" or "extended release" or "prolonged release" have been used interchangeably and mean broadly that Ipragliflozin.
The term “pharmaceutically acceptable” as used herein means that which is useful in preparing a pharmaceutical composition that is generally safe and non-toxic.
The term “excipients” as used herein means a component of a pharmaceutical product that is not an active ingredient such as, for example, fillers, diluents, carriers and the like. The excipients that are useful in preparing a pharmaceutical composition are generally safe and non-toxic.
By the term “composition” as used herein refers to a solid dosage form suitable for oral administration, such as a tablet, capsule, spheroids, mini-tablets, pellets, granules, pills and the like; preferably, oral tablets.
Diluents according to the present invention include but not limited to lactose monohydrate, lactose anhydrous, fructose, dextrose, dextrates, dextrins, mannitol, lactitol, sorbitol, starch, sucrose, calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, silicified microcrystalline cellulose, or combinations thereof.
Binders according to the present invention include but not limited to hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, gelatin, ethyl cellulose, polyvinyl alcohol, pregelatinized starch, carboxymethyl cellulose, Polysorbate 80, sodium alginate, microcrystalline cellulose, Calcium hydrogen phosphate and the like or combinations thereof.
Disintegrants according to the present invention include but not limited to starches or modified starches such as pregelatinized starch, croscarmellose sodium, crospovidone, sodium starch glycolate, low substituted hydroxypropyl cellulose, hydroxypropyl cellulose, chitosan and the like or combinations thereof.
Surfactants according to the present invention may be selected from anionic, cationic or non- ionic surface-active agents or surfactants. Suitable anionic surfactants include but not limited to carboxylate, sulfonate, and sulfate ions such as sodium lauryl sulfate (SLS), sodium laurate, dialkyl sodium sulfosuccinates particularly bis- (2-ethylhexyl) sodium sulfosuccinate, sodium stearate, potassium stearate, sodium oleate and the like. Suitable cationic surfactants include but not limited to those containing long chain cations, such as benzalkonium chloride, bis-2- hydroxyethyl oleyl amine or the like.
Lubricants and/or glidants according to the present invention include but not limited to colloidal silicon dioxide, stearic acid, magnesium stearate, Syloid XDP, calcium stearate, sodium stearyl fumarate, talc, hydrogenated castor oil, and mixtures thereof.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients and processes for the preparation of the pharmaceutical composition.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. Where in the composition comprising a solid dispersion of Ipragliflozin and one or more pharmaceutically acceptable excipients.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, where in the composition comprising a solid dispersion of Ipragliflozin and a carrier, wherein the Ipragliflozin is dispersed or dissolved in the carrier.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in the pharmaceutical composition is oral solid dosage form.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients. where in formulations is prepared into powders, granules and tablets, methods for manufacturing and processing the powders, granules and tablets.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, one or more pharmaceutically acceptable excipients, wherein the Ipragliflozin having 5-70% w/w of the composition.
In one of the embodiments of the present invention relates to a process for the preparation of Ipragliflozin and one or more pharmaceutically acceptable excipients having comparable dissolution properties, content uniformity, stability and equivalent bioavailability w.r.t commercialized Ipragliflozin dosage form.
In one of the embodiments of the present invention relates to a pharmaceutical compositions comprising Ipragliflozin or its pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable excipients like diluent, binder, glidant, lubricant, solubilizer, antacid, disintegrant and colorant.
In one of the embodiments of the present invention is to provide a method for treatment of a diabetes by administering an immediate release pharmaceutical formulation comprising Ipragliflozin and its pharmaceutically acceptable salts.
In one of the embodiments of the Present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in the particle size of Ipragliflozin is less than 250 microns, preferably less than 100 microns, more preferably less than 50 microns.
In one of the embodiments of the Present invention relates to a pharmaceutical composition comprising Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in Ipragliflozin is in the form of crystalline of amorphous form.
Examples
The following examples are for the purpose of illustration of the invention only and are not intended in any way to limit the scope of the present invention.

Example 1:
S. No Ingredients Qty/ Tablet (mg)
1. Ipragliflozin 50 Mg
2. Chitosan 18 Mg
3. Calcium hydrogen phosphate 16 Mg
4. Microcrystalline Cellulose 50 Mg
5. Povidone K30 10 Mg
6. Micro powder Silica Gel 16 Mg
7. Magnesium Stearate 2 Mg

Manufacturing process:

In the first step, Ipragliflozin is passed through an 80-mesh sieve, and other excipients are passed through a 60-mesh sieve;
The second step is to weigh the sieved glimepiride, microcrystalline cellulose, micro powder silica gel, magnesium stearate, and chitosan of one-half of the recipe and mix them evenly with one-half of the recipe. The povidone k30 aqueous solution is used as a binder and granulated;
The third step is drying the particles obtained in the second step, drying at 60°C, pulverizing, and passing through an 80-mesh sieve;
The granules obtained in the fourth step and the third step are mixed with the prescribed amount of calcium hydrogen phosphate, the remaining one-half of the prescribed amount of chitosan, and the prescribed amount of Ipragliflozin. The povidone k30 aqueous solution of the prescription amount is used as a binder, granulated, dried, granulated, and passed through an 80-mesh sieve.
The granules obtained in the fifth step and the fourth step are mixed with the prescribed amount of magnesium stearate and compressed into tablets.
,CLAIMS:1) A pharmaceutical composition comprising a solid dispersion of Ipragliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, wherein the Ipragliflozin is 5-70% w/w of the total weight of the composition.

2) The pharmaceutical composition as claimed in claim 1, wherein solid dispersion is a mixture of Ipragliflozin and a carrier, wherein the Ipragliflozin is dispersed or dissolved in the carrier.

3) The pharmaceutical composition as claimed in claim 1, wherein the composition comprising of Ipragliflozin solid dispersion and one or more pharmaceutically acceptable excipients like diluent, binder, glidant, lubricant, solubilizer, antacid, disintegrant and colorant.

4) The pharmaceutical composition as claimed in claim 1, wherein the composition is comprising of Ipragliflozin solid dispersion and one or more pharmaceutically acceptable excipients like chitosan, calcium hydrogen phosphate, microcrystalline cellulose, povidone, micro powder silica gel, magnesium stearate.

5) The pharmaceutical composition as claimed in claim 1, where in Ipragliflozin having particle size is less than 250 microns, preferably less than 100 microns, more preferably less than 50 microns.

6) The pharmaceutical composition as claimed in claim 1, wherein Ipragliflozin is in the form of crystalline or amorphous form.

7) The pharmaceutical composition as claimed in claim 1, wherein Ipragliflozin formulations is in the form of powders, granules or tablets.

8) The pharmaceutical composition as claimed in claim 1, wherein Ipragliflozin formulations is prepared by direct compression, wet granulation or dry granulation.

9) The pharmaceutical composition as claimed in claim 1, where in the composition is used for the treatment of type 2 diabetes.