Composite formulation comprising sitagliptin and dapagliflozin and preparation method therefor
Provided are a composite formulation including sitagliptin and dapagliflozin and a method of preparing the same.
1 . A composite formulation comprising:
(A) dry granules prepared by dry-granulation using a roller compactor, said dry granules comprising:
a) sitagliptin or a pharmaceutically acceptable salt thereof, or a hydrate thereof;
b) dapagliflozin or a pharmaceutically acceptable salt thereof, or a hydrate thereof; and
c) 1 wt % to 5 wt % of sodium stearyl fumarate as a lubricant, based on a total weight of the composite formulation, and
(B) additional sodium stearyl fumarate as a lubricant present outside of the dry granules,
wherein a total amount of sodium stearyl fumarate present in the composite formulation is 3 wt % to 8 wt %, based on the total weight of the composite formulation.
2 . The composite formulation of claim 1 , wherein the sitagliptin or a pharmaceutically acceptable salt thereof, or a hydrate thereof, is sitagliptin phosphate hydrate.
3 . The composite formulation of claim 1 , wherein the dapagliflozin or a pharmaceutically acceptable salt thereof, or a hydrate thereof, is dapagliflozin L-proline or dapagliflozin propanediol.
4 . The composite formulation of claim 1 , further comprising an excipient selected from microcrystalline cellulose (MCC), mannitol, pregelatinized starch, low-substituted hydroxypropyl cellulose (L-HPC), crospovidone, cross-linked carboxymethyl cellulose sodium (cross-linked CMC Na), and any mixtures thereof.
5 . The composite formulation of claim 1 , wherein the dry granules further comprise 5 wt % to 20 wt % of low-substituted hydroxypropyl cellulose (L-HPC) as a disintegrant, based on the total weight of the composite formulation.
6 . The composite formulation of claim 1 , wherein the dry granules further comprise water in an amount of 5 wt % or less, based on the total weight of the composite formulation.
7 . The composite formulation of claim 1 , wherein the composite formulation is in a form of a tablet, a capsule, or granules.
8 . The composite formulation of claim 1 , wherein the sitagliptin or a pharmaceutically acceptable salt thereof, or a hydrate thereof, is comprised in an amount of 10 wt % to 40 wt %, based on the total weight of the composite formulation.
9 . The composite formulation of claim 1 , wherein the dapagliflozin or a pharmaceutically acceptable salt thereof, or a hydrate thereof is comprised in an amount of 2 wt % to 10 wt %, based on the total weight of the composite formulation.
10 . The composite formulation of claim 1 , further comprising metformin or a pharmaceutically acceptable salt thereof, or a hydrate thereof.
11 . A method of preparing the composite formulation of claim 1 , the method comprising:
(a) preparing a mixture portion comprising sitagliptin or a pharmaceutically acceptable salt thereof, or a hydrate thereof, and dapagliflozin or a pharmaceutically acceptable salt thereof, or a hydrate thereof, and 1 wt % to 5 wt % of a first portion of sodium stearyl fumarate as a lubricant, based on the total weight of the composite formulation;
(b) dry-granulating the mixture portion using a roller compactor; and
(c) further adding a second portion of sodium stearyl fumarate as a lubricant to the granulated material and mixing together,
wherein a total amount of sodium stearyl fumarate present in the composite formulation is 3 wt % to 8 wt %, based on the total weight of the composite formulation.
12 . The method of claim 11 , further comprising tableting the granulated material mixed with sodium stearyl fumarate of step (c).
13 . The method of claim 11 , wherein the mixture portion further comprises an excipient selected from microcrystalline cellulose (MCC), mannitol, pregelatinized starch, low-substituted hydroxypropyl cellulose (L-HPC), crospovidone, cross-linked carboxymethyl cellulose sodium (cross-linked CMC Na), and any mixtures thereof.