Spironolactone Aqueous Compositions
Disclosed herein is a stable, ready-to-use liquid formulation comprising spironolactone and its method of use.
1 . A process for preparing a pharmaceutical composition, which comprises:
(a) mixing in a first container a first composition comprising a hydrocolloid, an anti-foaming agent, a preservative, and water;
(b) mixing in a second container a second composition comprising micronized spironolactone glycerin, and water;
(c) transferring the second composition from the second container to the first container followed by mixing to obtain a third composition; and
(d) adding a flavoring agent and water to the first container from step (c) to obtain a fourth composition;
wherein the pharmaceutical composition comprises 5 mg/mL micronized spironolactone; and
wherein the pharmaceutical composition comprises from 18 mg/mL to 24 mg/mL glycerin.
2 . The process of claim 1 , wherein the micronized spironolactone has a median volume particle size of not more than about 9.6 μm.
3 . The process of claim 1 , wherein the micronized spironolactone has a median volume particle size of about 3.6 μm to about 9.6 μm.
4 . The process of claim 1 , wherein the hydrocolloid comprises xanthan gum, methylcellulose, magnesium aluminum silicate, or a combination thereof.
5 . The process of claim 1 , wherein the hydrocolloid is present in an amount to provide a pharmaceutical composition viscosity of from 100 cP to 300 cP.
6 . The process of claim 1 , wherein the hydrocolloid is present in an amount to provide a pharmaceutical composition viscosity of from 130 cP to 170 cP.
7 . The process of claim 1 , wherein the hydrocolloid comprises xanthan gum in an amount to provide a xanthan gum content of the pharmaceutical composition of from 1.3 mg/mL to 3.6 mg/mL.
8 . The process of claim 1 , wherein the hydrocolloid comprises xanthan gum in an amount to provide a xanthan gum content of the pharmaceutical composition of from 1.3 mg/mL to 3.0 mg/mL.
9 . The process of claim 1 , wherein the anti-foaming agent comprises a simethicone emulsion.
10 . The process of claim 1 , wherein the preservative comprises sorbic acid or a pharmaceutically acceptable salt thereof.
11 . The process of claim 1 , wherein the preservative comprises sorbic acid, potassium sorbate, or a combination thereof.
12 . The process of claim 1 , wherein the pharmaceutical composition comprises from 18 mg/mL to 22 mg/mL glycerin.
13 . The process of claim 1 , which further comprises adding a sweetening agent to the first composition, the second composition, or a combination thereof.
14 . The process of claim 12 , wherein the sweetening agent saccharin sodium, ammonium glycyrrhizinate, or a combination thereof.
15 . The process of claim 1 , which further comprises adding a buffer to the first composition, the fourth composition, or a combination thereof.
16 . The process of claim 15 , wherein the pharmaceutical composition has a pH of from 4.5 to 5.5.
17 . The process of claim 15 , wherein the pharmaceutical composition has a pH of from 4.8 to 5.2.
18 . The process of claim 15 , wherein the pharmaceutical composition has a pH of from 4.8 to 5.0.
19 . The process of claim 15 , wherein the pharmaceutical composition has a buffer concentration of from about 10 mM to about 100 mM.
20 . The process of claim 15 , wherein the pharmaceutical composition has a buffer concentration of from about 10 mM to about 100 mM and wherein the buffer is selected from acetate, aconitate, glutarate, glutamate, malate, succinate, tartrate, citrate, and phosphate.
21 . The process of claim 1 , which further comprises dispensing the fourth composition into an amber polyethylene terephthalate bottle.
22 . The process of claim 21 , wherein the volume of the bottle is about 118 mL.
23 . The process of claim 21 , wherein the volume of the bottle is about 473 mL.