Oral solid chlorthalidone compositions
Described herein are solid oral compositions comprising chlorthalidone, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient, wherein the chlorthalidone has a Sauter mean diameter ranging from about 8 μm to about 14 μm. Methods of making and using these compositions are also described herein.
1 . A solid oral composition comprising:
chlorthalidone, or a pharmaceutically acceptable salt thereof, having:
a Sauter's mean diameter (D 3,2 ) of from 8 μm to 14 μm; and
a specific surface area of from 0.25 m 2 /gram to 0.5 m 2 /gram; and
a pharmaceutically acceptable carrier;
wherein the pharmaceutically acceptable carrier comprises:
about 40% w/w of microcrystalline cellulose;
about 7% w/w sodium starch glycolate;
about 15% w/w pregelatinized starch;
about 1% w/w of colloidal silicon dioxide; and
about 0.9% w/w of calcium stearate;
wherein the solid oral composition releases not less than 58% of chlorthalidone within 15 minutes in dissolution media having a pH of 1.2, 4.5, or 6.8; and
wherein the dissolution testing is conducted in a USP Type I basket apparatus at 100 rpm in 500 ml of dissolution media maintained at 37±0.5° C.
2 . The solid oral composition according to claim 1 , wherein the pharmaceutically acceptable carrier comprises:
40.21% w/w of microcrystalline cellulose;
7.14% w/w of sodium starch glycolate;
15% w/w of pregelatinized starch;
1% w/w of colloidal silicon dioxide; and
0.93% w/w of calcium stearate.
3 . The solid oral composition according to claim 1 , wherein the solid oral composition is in the form of a tablet.
4 . The solid oral composition according to claim 3 , wherein the tablet substantially disintegrates in the dissolution media in less than 30 seconds.
5 . The solid oral composition according to claim 3 , wherein the tablet comprises 12.5 mg of chlorthalidone, or a pharmaceutically acceptable salt thereof.
6 . The solid oral composition according to claim 3 , wherein the tablet is unscored and administered to the subject without splitting.
7 . The solid oral composition according to claim 1 , wherein the solid oral composition releases not less than 80% of chlorthalidone, or a pharmaceutically acceptable salt thereof, within 30 minutes.
8 . The solid oral composition according to claim 1 , wherein the solid oral composition releases not less than 84% of chlorthalidone, or a pharmaceutically acceptable salt thereof, within 45 minutes.
9 . The solid oral composition according to claim 1 , wherein the solid oral composition releases not less than 90% of chlorthalidone, or a pharmaceutically acceptable salt thereof, within 60 minutes.
10 . The solid oral composition according to claim 1 , wherein after storage at 25° C. and 60% relative humidity for at least 12 months, or after storage at 40° C. and 75% relative humidity for 6 months, the solid oral composition has:
(a) total impurities in an amount that does not exceed about 1%; and
(b) chlorthalidone ethyl ether impurity in an amount that does not exceed about 0.1%;
wherein the impurity concentrations are calculated based on the weight of chlorthalidone.
11 . The solid oral composition according to claim 1 , wherein after storage at 25° C. and 60% relative humidity for at least 24 months, the solid oral composition has:
(a) total impurities in an amount that does not exceed about 1%; and
(b) chlorthalidone ethyl ether impurity in an amount that does not exceed about 0.1%;
wherein the impurity concentrations are calculated based on the weight of chlorthalidone.
12 . The solid oral composition according to claim 1 , wherein after storage at 25° C. and 60% relative humidity for at least 36 months, the solid oral composition has:
(a) total impurities in an amount that does not exceed about 1%; and
(b) chlorthalidone ethyl ether impurity in an amount that does not exceed about 0.1%;
wherein the impurity concentrations are calculated based on the weight of chlorthalidone.