DESC:The present invention relates to an oral pharmaceutical composition comprising Dapagliflozin or its pharmaceutically acceptable salt thereof and one or more pharmaceutical acceptable excipients.
The present invention relates to a pharmaceutical tablet dosage form composition comprising an intra-granular portion and an extra-granular portion, the intra-granular portion comprising Dapagliflozin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients and the extra-granular portion comprising one or more pharmaceutically acceptable excipients, wherein the granulation fluid is prepared by adding the pharmaceutical acceptable excipients with Dapagliflozin or its pharmaceutically acceptable salts, blend and compress the above blend by using suitable punches, Prepare the film coating dispersion by dispersing in purified water under stirring and coat the compressed tablets
According to the embodiments of the present invention intra-granular portion comprising Dapagliflozin or its pharmaceutically acceptable salts dissolved in a solvent or mixture of solvents and pharmaceutically acceptable excipients are selected from diluent, binder and disintegrant.
According to the embodiments of the present invention extra-granular portion comprising pharmaceutically acceptable excipients are selected from diluent, disintegrant and lubricant.
The term "pharmaceutical acceptable excipient" as used herein refers to additives useful for converting pharmacologically active compounds into pharmaceutical dosage forms which are suitable for administration to patients. Suitable excipients include diluents, binders, disintegrant, surfactants, lubricants, glidants and coloring agents. Other pharmaceutically acceptable excipients can also be included.
The term “composition” or “pharmaceutical composition” or “solid dosage forms” such as granules, multiunit particulate systems (MUPS), pellets, spheres, tablets, capsules, mini-tablets, beads, particles and the like; and liquid dosage forms such as solutions, suspensions, emulsions, colloids and the like, meant for oral administration.
The term “Dapagliflozin” as used herein means Dapagliflozin or its pharmaceutically acceptable salts. Dapagliflozin may be in amorphous form, crystalline form, a mixture thereof or co-crystals with suitable co-formers. Preferably, Dapagliflozin base is in amorphous form.
The articles "a" and "an" are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "a diluent" means one diluent or more than one diluent.
Throughout this specification and the appended claims, it is to be understood that the words "comprise", “have”, “contain” and "include" and variations such a "comprises", "comprising", “having”, “containing” "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.
In the embodiments of the present invention provides process for the preparation of oral pharmaceutical compositions, wherein the method of manufacturing comprises Co-sift Microcrystalline cellulose, hydroxypropyl methyl cellulose E5 (HPMC) and anhydrous lactose through mesh ,add Isopropyl alcohol and Dichloromethane in the ratio of (80:20) in a SS vessel and add weighed quantity of Dapagliflozin and kept under continuous stirring till clear solution appears, Granulate the above process to attain desired granules and dried the wet granules to attain desired granules and mill with 1.00 mm screen until all the dried granules passes through mesh, Sift Microcrystalline cellulose, Crospovidone and Colloidal silicon dioxide through mesh and blend with above process in a suitable blender up to 10 minutes, Sift Magnesium stearate through mesh, blend the above process for 5 minutes, Finally Compressed into tablets and Film coated.
According to the embodiments of the present invention diluent are selected from the group comprising of, Micro crystalline cellulose, starch, pregelatinized starch, calcium carbonate, dibasic, tribasic calcium phosphate, calcium phosphate, lactose, dextrose, calcium phosphate, fructose, lactitol, lactose, magnesium carbonate, magnesium oxide, maltitol, maltose, simethicone, sodium chloride, talc, xylitol, sorbitol, mannitol, maltodextrin and mixtures thereof.
According to the embodiments of the present invention suitable binders used according to the present invention are selected from the group comprising of hydroxypropylmethylcellulose, maize starch, povidone, hydroxypropylcellulose, pregelatinized starch and the like or combination thereof.
According to the embodiments of the present invention disintegrant are selected from the group comprising of starches, croscarmellose sodium, carmellose, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, sodium alginate, low-substituted hydroxypropylcellulose, crospovidone and mixtures thereof.
According to the embodiments of the present invention suitable surfactants are selected from Tyloxapol®, Triton X-100®, polysorbates, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 40 stearates, sorbitan monolaureates, sodium lauryl sulphate, polyethylene-propylene glycol copolymer (poloxamer), cremophor-40, propylene glycol and mixtures thereof.
According to the embodiments of the present invention lubricant selected for the group anti-tacking agent, sodium lauryl sulphate, metallic stearates such as magnesium stearate, calcium stearate, zinc stearate; stearic acid, hydrogenated vegetable oil, hydrogenated castor oil, glycerylpalmitostearate, glyceryl behenate, polyethylene glycols, corn starch, sodium stearylfumarate, sodium benzoate, mineral oil, glycerine fumarate and mixtures thereof.
According to the embodiments of the present invention suitable film coating polymers used according to the present invention are selected from polyvinyl alcohol (part hydrolyzed), titanium dioxide, macrogol (polyethylene glycol 3350), Hypromellose, Lactose, Triacetin, Talc, Titanium oxide and iron oxide and the like or mixtures thereof.
In embodiments of the present invention provides process for the preparation of oral pharmaceutical compositions, wherein the method of manufacturing comprises Co-sift Microcrystalline cellulose, hydroxypropyl methyl cellulose E5 (HPMC) and anhydrous lactose through mesh ,add Isopropyl alcohol and Dichloromethane in the ratio of (80:20) in a SS vessel and add weighed quantity of Dapagliflozin and kept under continuous stirring till clear solution appears, Granulate the above process to attain desired granules and dried the wet granules to attain desired granules and mill with 1.00 mm screen until all the dried granules passes through mesh, Sift Microcrystalline cellulose, Crospovidone and Colloidal silicon dioxide through mesh and blend with above process in a suitable blender up to 10 minutes, Sift Magnesium stearate through mesh, blend the above process for 5 minutes, Finally Compressed into tablets and Film coated.
According to embodiment of the present invention composition will provide stable product, as well as improved dissolution profile and bioavailability.
According to embodiment of the present invention the granulation fluid contains a solvent or carrier material which must be volatile so that it can be removed by drying.
According to the embodiments of the present invention, a pharmaceutical stable dosage form composition comprising immediate release tablet.
The process details of the invention are provided in the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.
,CLAIMS:1. A solid oral pharmaceutical composition comprising
a) An Intra-granular portion containing Dapagliflozin or its pharmaceutically acceptable salts thereof and one or more pharmaceutical acceptable excipients; and
b) An extra-granular portion containing one or more pharmaceutically acceptable excipients thereof. Where in Dapagliflozin is incorporated in the formulation by dissolving in granulation fluid.

2. A solid oral pharmaceutical composition as claimed in claim 1, wherein the granulation fluid is prepared by adding the pharmaceutical acceptable excipients with Dapagliflozin or its pharmaceutically acceptable salts optionally along with binder.

3. A solid oral pharmaceutical composition as claimed in claim 1, wherein the Intra-granular portion comprising pharmaceutical acceptable excipients in an amount of 50%- 90% based on the total weight of the composition.

4. A solid oral pharmaceutical composition as claimed in claim 1, wherein the Extra-granular portion comprising pharmaceutical acceptable excipients in an amount of 10%- 25% based on the total weight of the composition.

5. A solid oral pharmaceutical composition as claimed in claim 1, wherein the pharmaceutically acceptable excipients are selected from diluents, binders, disintegrants, surfactants, lubricants, glidants and colouring agents and the like or mixture thereof and optionally a pharmaceutical acceptable excipient.

6. A process for preparation of solid oral pharmaceutical composition comprising of Dapagliflozin or its pharmaceutically acceptable salts where in the Dapagliflozin is dissolved in the granulation fluid and granulated with other pharmaceutical acceptable excipients.

7. A process for preparation of solid oral pharmaceutical composition as claimed in claim 6, the granulation fluid is selected from the group consisting of organic solvents such as isopropyl alcohol (IPA), acetone, ethanol, dichloromethane or mixtures thereof.

8. A solid oral pharmaceutical composition as claimed in claim 1, wherein composition comprising Dapagliflozin or its pharmaceutically acceptable salts is prepared by granulation technique; preferably wet granulation.

9. A solid oral pharmaceutical composition as claimed in claim 1, where the oral dosage form is more preferably immediate release tablet dosage form.

10. A solid oral pharmaceutical composition as claimed in claim 1, wherein preferably excipients are selected from Microcrystalline cellulose, Anhydrous lactose, Hydroxy propyl methyl cellulose, Isopropyl alcohol, Dichloromethane, Crospovidone, Colloidal silicon dioxide, Magnesium stearate.