LIQUID GUAIFENESIN COMPOSITIONS WITH STABLE EXTENDED RELEASE PROFILES
The present disclosure provides drug-containing sustained-release particles that have minimal loss of the drug from the particle when the particle is formulated as a suspension in a liquid phase that is saturated by the drug.
1 . A sustained-release particle comprising a core, a first coating, and a second coating, wherein:
the core comprises guaifenesin;
the first coating comprises about 90 wt % or more of one or more hydrophilic polymers and covers the core to form an intermediate particle, wherein the coating ratio of the first coating is about 5 wt % to about 15 wt % of the intermediate particle;
the second coating comprises about 80 wt % or more of one or more hydrophobic, sustained-release polymers, less than about 15 wt % of a plasticizer, and the second coating covers the first coating.
2 .- 32 . (canceled)
33 . A pharmaceutical composition comprising a plurality of sustained release particles dispersed in a liquid phase wherein:
the plurality of sustained release particles consists of particles according to claim 1 ;
the composition comprises at least about 10% of the guaifenesin in the form of an immediate-release (IR) fraction; and
the amount of guaifenesin in 1 ml of the composition is about 60 mg to about 240 mg.
34 . The pharmaceutical composition of claim 33 , wherein the amount of guaifenesin in 1 ml of the composition is about 120 mg.
35 . The pharmaceutical composition of claim 33 , wherein the guaifenesin in the IR fraction is about 5% to 50% of the total amount of guaifenesin.
36 . The pharmaceutical composition of claim 35 , wherein the guaifenesin in the IR fraction is about 15% to 25% of the total amount of guaifenesin.
37 . The pharmaceutical composition of claim 33 , wherein the liquid phase further comprises one or more osmotic agent and/or crystallization inhibitor.
38 . The pharmaceutical composition of claim 37 , wherein an osmotic agent is a salt, a sugar alcohol, citrate, polydextrose, fructose, glucose, maltose, or sucrose.
39 . The pharmaceutical composition of claim 38 , wherein the sugar alcohol is maltitol, sorbitol, erythritol, xylitol, or combinations thereof.
40 . The pharmaceutical composition of claim 37 , wherein the amount of the osmotic agent is about 30 wt % to about 80 wt % of the composition.
41 . The pharmaceutical composition of claim 37 , wherein the crystallization inhibitor is polyvinylpyrrolidone, optionally in an amount that is about 0.1 wt % to about 5 wt % of the composition.
42 . The pharmaceutical composition of claim 33 , wherein the liquid phase further comprises one or more of a suspending agent, a preservative, a pH modifier, an antimicrobial agent, and a flavor modifying agent.
43 . The pharmaceutical composition of claim 42 , wherein the amount of the suspending agent is about 0.1 wt % to about 5 wt % of the composition, preferably about 0.1 wt % to about 2 wt % of the composition, more preferably about 0.5 wt % to about 2 wt % of the composition.
44 . The pharmaceutical composition of claim 42 , wherein the suspending agent is microcrystalline cellulose and carboxymethylcellulose sodium, xanthan gum, or a combination thereof.
45 . The pharmaceutical composition of claim 42 , wherein the preservative is benzoic acid or a salt thereof, sorbic acid or a salt thereof, benzyl alcohol, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, or a quaternary ammonium salt, alcohol or phenol.
46 . The pharmaceutical composition of claim 36 , wherein after storage for at least three months at about 30° C. and 65% relative humidity, the composition has a stable in vitro dissolution profile.
47 . The pharmaceutical composition of claim 46 , wherein the composition has a stable in vitro dissolution profile for at least 6 months.
48 . The pharmaceutical composition of claim 46 , wherein the composition has a stable in vitro dissolution profile for at least 12 months.
49 . The pharmaceutical composition of claim 46 , wherein the composition has a stable in vitro dissolution profile for at least 2 years.
50 . The pharmaceutical composition of claim 46 , wherein the stable in vitro dissolution profile is evaluated by comparing a fraction of guaifenesin released at 30 min to an initial suspension.
51 . The pharmaceutical composition of claim 50 , wherein the fraction of the guaifenesin released at 30 min does not differ by more than ±10% from the fraction released for the same time in the initial suspension.
52 . The pharmaceutical composition of claim 46 , wherein the stable in vitro dissolution profile is evaluated by calculating an f 2 value.
53 . The pharmaceutical composition of claim 52 , wherein the f 2 value is greater than 50.
54 . A method of treating coughing, symptoms of coughing, nasal discharge, congestion or sneezing associated with a cold, flu or an allergy comprising administering to a human subject in need thereof a single dose of a pharmaceutical composition of claim 33 .