Pharmaceutical Formulation
A pharmaceutical composition in the form of a tablet including a first portion and a second portion, wherein the first portion includes guaifenesin having an immediate release profile and a second drug having a sustained release profile, and wherein the second portion includes guaifenesin having a sustained release profile. The second drug can be in the form of a drug-resin complex. The second drug can be either an anti-tussive or a decongestant. The drug-resin complex includes a drug complexed to an ion exchange resin. The ion exchange resin can be a polystyrene sulfonate resin, polacrilex resin, polacrilin potassium, cholestyramine resin, or a colestyramine resin. The drug-resin complex can be provided with a coating, the coating thickness being selected to obtain the desired release profile. The drug-resin complex can be provided with a coating level of from 5% to 50%. The coating level can be from 10% to 35%.
1 . A pharmaceutical composition comprising:
a first portion; and
a second portion;
wherein the first portion comprises guaifenesin having an immediate release profile and a second drug having a sustained release profile; and
wherein the second portion comprises guaifenesin having a sustained release profile.
2 . The pharmaceutical composition as claimed in claim 1 , wherein the second portion comprises a release-delaying matrix comprising a hydrophilic polymer and a water-insoluble polymer.
3 . The pharmaceutical composition as claimed in claim 1 , wherein the second drug comprises codeine.
4 . The pharmaceutical composition as claimed in claim 2 , wherein the hydrophilic polymer comprises hydroxypropyl methylcellulose.
5 . The pharmaceutical composition as claimed in claim 2 , wherein the water-insoluble polymer comprises a carbomer.
6 . The pharmaceutical composition as claimed in claim 1 , wherein the second drug is in the form of a coated drug-resin complex.
7 . The pharmaceutical composition as claimed in claim 1 , wherein the second drug is selected from the group consisting of an anti-tussive and a decongestant.
8 . The pharmaceutical composition as claimed in claim 1 , wherein the second drug is selected from the group consisting of codeine, pseudoephedrine, phenylephrine, dextromethorphan and hydrocodone.
9 . The pharmaceutical composition as claimed in claim 6 , wherein the coated drug-resin complex comprises an ion exchange resin.
10 . The pharmaceutical composition as claimed in claim 9 , wherein the ion exchange resin is selected from the group consisting of a polystyrene sulfonate resin, polacrilex resin, polacrilin potassium, cholestyramine resin, a colestyramine resin, and a sodium polystyrene sulfonate resin.
11 . The pharmaceutical composition as claimed in claim 6 , wherein the coating level of the coated drug-resin complex is from 5% to 50%.
12 . The pharmaceutical composition as claimed in claim 11 , wherein the coating level is from 10% to 35%.
13 . A pharmaceutical composition comprising:
a first portion; and
a second portion;
wherein the first portion comprises guaifenesin having an immediate release profile and a second drug in the form of a coated drug-resin complex having a sustained release profile; and
wherein the second portion comprises guaifenesin having a sustained release profile.
14 . The pharmaceutical composition as claimed in claim 13 , wherein the coated drug-resin complex comprises a coated codeine polistirex complex.
15 . The pharmaceutical composition as claimed in claim 13 , wherein the coated drug resin complex has a coating level of 30% and has the following dissolution profile in USP apparatus 1 (baskets) at 50 rpm in 0.1N HCl at 37° C.:
Time (hours)
Average % Codeine released
1
18-48
2
27-57
6
42-72
12
51-81
16 . The pharmaceutical composition as claimed in claim 13 , wherein the coated drug resin complex has a coating level of 30% and has the following dissolution profile in USP apparatus 1 (baskets) at 50 rpm in 0.1N HCl at 37° C.:
Time (hours)
Average % Codeine released
1
33
2
42
6
57
12
66
17 . The pharmaceutical composition as claimed in claim 13 , wherein the coated drug resin complex has a coating level of 15% and has the following dissolution profile in USP apparatus 1 (baskets) at 50 rpm in 0.1N HCl at 37° C.:
Time (hours)
Average % Codeine released
1
30-60
2
43-73
6
64-94
12
at least 73
18 . The pharmaceutical composition as claimed in claim 13 , wherein the coated drug resin complex has a coating level of 15% and has the following dissolution profile in USP apparatus 1 (baskets) at 50 rpm in 0.1N HCl at 37° C.:
Time (hours)
Average % Codeine released
1
45
2
58
6
79
12
88
19 . A pharmaceutical composition comprising:
a first portion; and
a second portion;
wherein the first portion comprises guaifenesin having an immediate release profile and a second drug having a sustained release profile;
wherein the second portion comprises guaifenesin having a sustained release profile;
wherein the total amount of guaifenesin is between 500 mg and 1300 mg;
wherein the total amount of the second drug is up to 100 mg; and
wherein the ratio of the total quantity of guaifenesin to the second drug in the same portion is from 1:1 to 30:1 (by weight).
20 . The pharmaceutical composition as claimed in claim 19 , wherein the second portion comprises a release-delaying matrix comprising a hydrophilic polymer and a water-insoluble polymer.
21 . The pharmaceutical composition as claimed in claim 19 , wherein the second drug comprises codeine.
22 . The pharmaceutical composition as claimed in claim 20 , wherein the hydrophilic polymer comprises hydroxypropyl methylcellulose.
23 . The pharmaceutical composition as claimed in claim 20 , wherein the water-insoluble polymer comprises a carbomer.
24 . The pharmaceutical composition as claimed in claim 19 , wherein the second drug is in the form of a coated drug-resin complex.
25 . The pharmaceutical composition as claimed in claim 19 , wherein the second drug is selected from the group consisting of an anti-tussive and a decongestant.
26 . The pharmaceutical composition as claimed in claim 19 , wherein the second drug is selected from the group consisting of codeine, pseudoephedrine, phenylephrine, dextromethorphan and hydrocodone.
27 . The pharmaceutical composition as claimed in claim 24 , wherein the coated drug-resin complex comprises an ion exchange resin.
28 . The pharmaceutical composition as claimed in claim 27 , wherein the ion exchange resin is selected from the group consisting of a polystyrene sulfonate resin, polacrilex resin, polacrilin potassium, cholestyramine resin, a colestyramine resin, and a sodium polystyrene sulfonate resin.
29 . The pharmaceutical composition as claimed in claim 25 , wherein the coating level of the coated drug-resin complex is from 5% to 50%.
30 . The pharmaceutical composition as claimed in claim 29 , wherein the coating level is from 10% to 35%.
31 . The pharmaceutical composition as claimed in claim 19 , wherein the second drug is also the sustained release portion.
32 . The pharmaceutical composition as claimed in claim 20 , wherein the weight ratio of hydrophilic polymer to water-insoluble polymer is from 1:1 to 9:1.
33 . The pharmaceutical composition as claimed in claim 20 , wherein the weight ratio of hydrophilic polymer to water-insoluble polymer is from 3:2 to 6:1.
34 . The pharmaceutical composition as claimed in claim 20 , wherein the weight ratio of hydrophilic polymer to water-insoluble polymer is from 2:1 to 4:1.
35 . The pharmaceutical composition as claimed in claim 19 , wherein the total amount of guaifenesin is between 600 mg to 1200 mg.
36 . The pharmaceutical composition as claimed in claim 19 , wherein the formulation contains 1200 mg of guaifenesin.
37 . The pharmaceutical composition as claimed in claim 19 , wherein the formulation contains 600 mg of guaifenesin.
38 . The pharmaceutical composition as claimed in claim 19 , wherein the total amount of the second drug is between 20-80 mg.
39 . The pharmaceutical composition as claimed in claim 21 , wherein the composition contains an amount of codeine that is therapeutically equivalent to 60 mg of codeine phosphate.
40 . The pharmaceutical composition as claimed in claim 21 , wherein the composition contains an amount of codeine that is therapeutically equivalent to 30 mg of codeine phosphate.
41 . The pharmaceutical composition as claimed in claim 21 , wherein the composition comprises 600 mg of guaifenesin and an amount of codeine that is therapeutically equivalent to 30 mg of codeine phosphate.
42 . The pharmaceutical composition as claimed in claim 21 , wherein the composition comprises 600 mg of guaifenesin and an amount of codeine that is therapeutically equivalent to 30 mg of codeine phosphate.
43 . The pharmaceutical composition as claimed in claim 21 , wherein the immediate release portion comprises microcrystalline cellulose, crospovidone and magnesium stearate.
44 . The pharmaceutical composition as claimed in claim 21 , wherein ratio of the total quantity of guaifenesin to codeine in the same portion is from 1:1 to 25:1 (by weight).
45 . The pharmaceutical composition as claimed in claim 19 , wherein the ratio of the immediate release quantity of guaifenesin to the sustained release quantity of guaifenesin is from 1:1 to 1:15 (by weight).
46 . The pharmaceutical composition as claimed in claim 19 , wherein the ratio of the immediate release quantity of guaifenesin to the sustained release quantity of guaifenesin is from 2:3 to 1:11 (by weight).
47 . The pharmaceutical composition as claimed in claim 19 , wherein the at least 60% of guaifenesin particles used to make the pharmaceutical composition has a particle size in the range of from 25 μm to 2.0 mm.
48 . The pharmaceutical composition as claimed in claim 19 , wherein the formulation comprises immediate release and sustained release portions each comprising abutting planar layers which form a bi-layer tablet.
49 . The pharmaceutical composition as claimed in claim 19 , wherein the formulation comprises a capsule that contains discrete or associated immediate release and sustained release portions.
50 . The pharmaceutical composition as claimed in claim 19 , wherein the sustained release portion is coated by a layer of the immediate release portion.
51 . The pharmaceutical composition as claimed in claim 19 , wherein each drug in the formulation exhibits a therapeutic effect for a period of 12 hours.