Pharmaceutical composition comprising dapagliflozin
The present invention relates to solid oral pharmaceutical compositions comprising amorphous dapagliflozin. The invention further relates to a process for the preparation of the said pharmaceutical compositions. The said compositions are administered orally for the treatment of diabetes mellitus. The said compositions provide the desired immediate release of dapagliflozin and were found to be stable under accelerated conditions.
1. A pharmaceutical tablet composition comprising:
a) amorphous dapagliflozin having a d(0.5) in the range from 20 μm to 75 μm, and
b) one or more surfactants,
wherein (i) the weight ratio of dapagliflozin to the surfactant is from about 1:0.1 to 1:10, and (ii) the tablet is an immediate release tablet.
2. The composition as claimed in claim 1 , wherein the one or more surfactant is selected from the group consisting of micro-encapsulated polysorbate 80, polysorbate 80, polysorbate 85, polysorbate 65, polysorbate 60, polysorbate 40, polysorbate 20, polyoxyethylene castor oil derivatives polyoxyethylene hydrogenated castor oil, ethoxylated hydrogenated castor oil, phosphatidyl choline, phospholipids, medium chain triglycerides, docusate sodium, lecithin, glyceryl monostearate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, poloxamers, sodium lauryl sulfate, polyoxyethylene alkyl ethers, polyoxyethylene stearates, sorbitan fatty acid esters, sucrose esters of fatty acids, PEG-8 Caprylic-Capric glycerides, saturated polyglycolized glycerides, and tocopherol PEG succinate.
3. The composition as claimed in claim 1 , wherein the one or more surfactant is from about 0.1% to about 25% by weight of the composition.
4. The composition as claimed in claim 1 , wherein dapagliflozin is from about 0.1% to about 25% by weight of the composition.
5. The composition as claimed in claim 1 , wherein the composition further comprises at least one excipient selected from the group consisting of diluent, binder, disintegrating agent, lubricant, and glidant.
6. The composition as claimed in claim 5 , wherein the disintegrating agent is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, croscarmellose calcium, croscarmellose potassium, sodium carbonate, starch, starch 1500, modified starch, pregelatinized starch, crosslinked carboxymethyl starch, sodium hydrogen carbonate, hydroxypropyl cellulose, and mixtures thereof.
7. The composition as claimed in claim 1 , wherein the composition releases at least about 70% of dapagliflozin within 30 minutes.
8. The composition as claimed in claim 1 , wherein the composition is stable at 40° C. and 75% relative humidity for a period of at least six months.
9. The composition as claimed in claim 1 , wherein the composition is prepared by wet granulation, dry granulation, or direct compression.
10. The composition as claimed in claim 1 , wherein the composition is bioequivalent to an immediate release tablet of a crystalline form of dapagliflozin propylene glycol hydrate.
11. An immediate release tablet comprising:
a) amorphous dapagliflozin having a d(0.5) of 20 μm to 75 μm, and
b) a surfactant which is micro-encapsulated polysorbate 80, wherein (i) the weight ratio of dapagliflozin to the surfactant is from about 1:0.1 to 1:10, and (ii) the tablet, after storage at 40° C. and 75% relative humidity in a HDPE container or in an Alu-Alu blister for 6 months, contains no more than 1.0% of total dapagliflozin impurities.
12. The tablet of claim 11 , wherein (i) the tablet comprises 5 or 10 mg of dapagliflozin and (ii) the tablet, after storage at 40° C. and 75% relative humidity in a HDPE container or in an Alu-Alu blister for 6 months, contains more than 90% of the 5 or 10 mg dapagliflozin.