Novel pharmaceutical formulation

Abstract

The present invention is directed to a pharmaceutical composition comprising a pharmaceutically effective amount of guaifenesin, naproxen and at least one further active which is selected to be an antitussive, a decongestant or an antihistamine.

1 . A pharmaceutical composition comprising a pharmaceutically effective amount of guaifenesin, naproxen and at least one further active which is selected to be an antitussive, a decongestant or an antihistamine. 
     
     
         2 . A composition as claimed in  claim 1 , wherein the at least one other drug is selected from an antitussive such as dextromethorphan, codeine, codeine phosphate, codeine sulphate, diphenhydramine citrate, and diphenhydramine hydrochloride, a decongestant such as phenylephrine hydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine or ephedrine, an antihistamine such as chlorpheniramine maleate, brompheniramine maleate, phenindamine tartrate, pyrilamine maleate, doxylamine succinate, phenyltoloxamine citrate, diphenhydramine hydrochloride, promethazine, and clemastine fumerate, or a combination thereof. 
     
     
         3 . A composition as claimed in  claim 2 , wherein the at least one other drug is dextromethorphan or pseudoephedrine. 
     
     
         4 . A composition as claimed in  claim 3 , wherein the expectorant is guaifenesin, the analgesic is naproxen and the antitussive is dextromethorphan. 
     
     
         5 . A composition as claimed in  claim 4 , wherein the ratio of guaifenesin:naproxen:dextromethorphan is from about 40:8:1 to about 10:3:1. 
     
     
         6 . A composition as claimed in  claim 5 , wherein the ratio of guaifenesin:naproxen:dextromethorphan is from 22:4:1 to 17:3:1. 
     
     
         7 . A composition as claimed in  claim 5 , wherein the ratio of guaifenesin:naproxen:dextromethorphan is 20:3.67:1. 
     
     
         8 . A composition as claimed in  claim 1 , wherein the ratio of guaifensin:naproxen is from about 1:1 to about 10:1. 
     
     
         9 . A composition as claimed in  claim 8 , wherein the ratio of guaifensin:naproxen is from about 2:1 to about 7:1. 
     
     
         10 . A composition as claimed in  claim 8 , wherein the ratio of guaifensin:naproxen is from about 4:1 to about 6:1. 
     
     
         11 . A composition as claimed in  claim 2 , wherein the ratio of naproxen:dextromethorphan is from about 1:1 to about 10:1. 
     
     
         12 . A composition as claimed in  claim 11 , wherein the ratio of naproxen:dextromethorphan is from about 2:1 to about 7:1. 
     
     
         13 . A composition as claimed in  claim 11 , wherein the ratio of wherein the ratio of naproxen:dextromethorphan is from about 3:1 to about 5:1. 
     
     
         14 . A composition as claimed in  claim 1 , wherein composition comprises immediate and sustained release portions. 
     
     
         15 . A composition as claimed in  claim 14 , wherein the composition is provided with both sustained-release and immediate-release portions comprising the expectorant. 
     
     
         16 . A composition as claimed in  claim 14 , wherein the naproxen is incorporated into the composition such that it is the sole active in the portion in which it is contained. 
     
     
         17 . A composition as claimed in  claim 14 , wherein the composition is provided with both sustained-release and immediate-release portions comprising guaifenesin. 
     
     
         18 . A composition as claimed in  claim 14 , wherein the composition comprises a first immediate release portion which comprises guaifenesin and a decongestant or an antitussive, a second immediate release portion which comprises naproxen, and a sustained release portion which comprises guaifenesin. 
     
     
         19 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 50-85% Guaifenesin;   (b) up to 5% Dextromethorphan or a pharmaceutically acceptable salt thereof; and   (c) 5-30% Naproxen or a pharmaceutically acceptable salt thereof.   
     
     
         20 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 55-65% Guaifenesin;   (b) 1-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 5-15% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1-10% Controlled release polymers;   (e) 0.1-10% Binders;   (f) 0.1-5% Disintegrants;   (g) 5-25% Diluents; and   (h) up to 1% Lubricants.   
     
     
         21 . A composition as claimed in  claim 20 , wherein the composition comprises:
 (a) 55-65% Guaifenesin;   (b) 1-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 5-15% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1-8% Hypromellose;   (e) 10-25% Microcrystalline cellulose;   (f) 0.1-2.5% Povidone;   (g) 0.1-4.0% Croscarmellose Sodium;   (h) 0.1-2.0% Hydroxyethyl Cellulose; and   (i) up to 1% Magnesium stearate.   
     
     
         22 . A composition as claimed in  claim 21 , wherein the composition comprises:
 (a) 58-63% Guaifenesin;   (b) 2-3.5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 10-12% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1-2% Hypromellose;   (e) 15-25% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 0.5-2.5% Croscarmellose sodium;   (h) 0.5-1% Hydroxyethyl cellulose; and   (i) up to 0.5% Magnesium stearate.   
     
     
         23 . A composition as claimed in  claim 20 , wherein the composition comprises:
 (a) 55-65% Guaifenesin;   (b) 1-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 5-15% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1-8% Hypromellose;   (e) 10-25% Microcrystalline cellulose;   (f) 0.1-2.5% Povidone;   (g) 0.1-2.0% Carbomer;   (h) 0.1-2.0% Sodium Starch Glycolate;   (i) up to 1% Magnesium stearate; and   
     
     
         24 . A composition as claimed in  claim 23 , wherein the composition comprises:
 (a) 59-65% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 10-12% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1-6% Hypromellose;   (e) 10-20% Microcrystalline cellulose;   (f) 0.3-1% Povidone;   (g) 0.5-1% Carbomer;   (h) 0.1-0.5% Sodium Starch Glycolate; and   (i) up to 1% Magnesium stearate.   
     
     
         25 . A composition as claimed in  claim 20 , wherein the composition comprises:
 (a) 59-65% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 10-12% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1-6% Hypromellose;   (e) 10-20% Microcrystalline cellulose;   (f) 0.3-1% Povidone;   (g) 0.5-1% Carbomer;   (h) 1-2% Croscarmellose sodium;   (i) 0.1-0.5% Sodium Starch Glycolate; and   (j) up to 1% Magnesium stearate.   
     
     
         26 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 64-69% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 12-15% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 3-5% Hypromellose;   (e) 9-15% Microcrystalline cellulose;   (f) 0.4-0.65% Povidone;   (g) 0.75-1.3% Carbomer;   (h) 0.5-1% Magnesium stearate; and   (i) 0.25-0.5% Sodium starch glycolate.   
     
     
         27 . A composition as claimed in  claim 26 , wherein the composition further comprises:
 (j) 0.5-1.5% Lactose;   (k) 2.5-3.5% Sodium lauryl sulphate; and   (l) 0.1-1.5% Croscarmellose sodium.   
     
     
         28 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 64-69% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 12-15% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 0.1-0.6% Hypromellose;   (e) 9-15% Microcrystalline cellulose;   (f) 0.4-0.65% Povidone;   (g) 0.75-1.3% Carbomer;   (h) 0.5-1% Magnesium stearate; and   (i) 0.25-0.5% Sodium starch glycolate.   
     
     
         29 . A composition as claimed in  claim 28 , wherein the composition further comprises one or more of:
 (j) 0.5-1.5% Lactose;   (k) 2.5-3.5% Sodium lauryl sulphate; and   (l) 0.1-1.5% Croscarmellose sodium.   
     
     
         30 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 63-66% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 10-12% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1.75-3.0% Hypromellose;   (e) 11-13% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 0.5-0.75% Croscarmellose Sodium;   (h) 1-2% Carbomer;   (i) 0.1-0.5% Magnesium stearate; and   (j) 0.5-1.5% Lactose.   
     
     
         31 . A composition as claimed in  claim 30 , wherein the composition further includes:
 (k) 2-3% Sodium Lauryl Sulphate.   
     
     
         32 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 64-66% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 11-13% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1.75-3.0% Hypromellose;   (e) 6-8.5% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 1-5% Croscarmellose Sodium;   (h) 0.5-1% Carbomer;   (i) 0.5-1% Magnesium stearate; and   (j) 0.5-1% Crospovidone.   
     
     
         33 . A composition as claimed in  claim 32 , wherein the composition further includes one or more of:
 (k) 2-3% Sodium Lauryl Sulphate; and   (l) 6-7% Sodium Bicarbonate.   
     
     
         34 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 64-66% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 11-13% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1.75-3.0% Hypromellose;   (e) 6-8.5% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 1-5% Croscarmellose Sodium;   (h) 0.5-1% Carbomer; and   (i) 0.5-1% Magnesium stearate.   
     
     
         35 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 62-65% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 11-13% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 1.75-3.0% Hypromellose;   (e) 6-8.5% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 1-5% Croscarmellose Sodium;   (h) 0.5-1% Carbomer; and   (i) 0.5-1% Magnesium stearate;   (j) 2-3% Sodium Lauryl Sulphate; and   (k) 5-8% Sodium Bicarbonate.   
     
     
         36 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 58-60% Guaifenesin;   (b) 2-3% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 10-11% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 2-3% Hypromellose;   (e) 7-8% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 2-3% Croscarmellose Sodium;   (h) 0.1-0.2% Magnesium stearate;   (i) 0.5-1% Crospovidone;   (j) 1-3% Hydroxyethyl cellulose;   (k) 2-3% Sodium Lauryl Sulphate; and   (l) 9-10% Sodium bicarbonate.   
     
     
         37 . A composition as claimed in  claim 1 , wherein the composition comprises:
 (a) 64-66% Guaifenesin;   (b) 3-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 11-13% Naproxen or a pharmaceutically acceptable salt thereof;   (d) 2-3% Hypromellose;   (e) 6-7% Microcrystalline cellulose;   (f) 1-2% Povidone;   (g) 0.1-0.5% Magnesium stearate;   (h) 7-10% Crospovidone; and   (i) 1-3% Hydroxyethyl cellulose.   
     
     
         38 . A pharmaceutical dosage form which comprises at least three distinct portions wherein two of the portions have immediate release characteristics and a third portion has modified release characteristics, wherein one of the immediate release portions comprises an expectorant and a second active which is an antitussive or a decongestant and the second immediate release portion comprises an analgesic having a half-life of twelve hours and wherein the modified release portion comprises guaifenesin and a second active which is an antitussive or a decongestant. 
     
     
         39 . A pharmaceutical dosage form as claimed in  claim 38 , wherein the dosage form comprises a first composition which comprises both immediate and modified release portions of the expectorant and the second active which is an antitussive or a decongestant and a second composition which comprises an analgesic having a therapeutic effect of twelve hours. 
     
     
         40 . A pharmaceutical dosage form as claimed in  claim 38 , wherein the analgesic is the sole active in the portion in which it is contained. 
     
     
         41 . A composition as claimed in  claim 1 , wherein an analgesic-containing immediate release portion comprises:
 (a) 50-52% Naproxen or a pharmaceutically acceptable salt thereof;   (b) 35-40% Microcrystalline cellulose;   (c) up to 5% Povidone;   (d) 5-8% Croscarmellose sodium; and   (e) up to 1% Magnesium stearate.   
     
     
         42 . A composition as claimed in  claim 1  wherein an analgesic-containing immediate release portion comprises:
 (a) 70-75% Naproxen or a pharmaceutically acceptable salt thereof; 
 (b) 20-25% Microcrystalline cellulose; 
 (c) up to 5% Povidone; and 
 (d) up to 1% Magnesium stearate. 
 
     
     
         43 . A composition as claimed in  claim 1 , wherein an analgesic-containing immediate release portion comprises:
 (a) 70-75% Naproxen or a pharmaceutically acceptable salt thereof;   (b) 5-10% Microcrystalline cellulose;   (c) up to 5% Povidone;   (d) up to 1% Magnesium stearate;   (e) 5-10% Lactose; and   (f) up to 5% Croscarmellose sodium.   
     
     
         44 . A composition as claimed in  claim 1 , wherein an analgesic-containing immediate release portion comprises:
 (a) 70-75% Naproxen or a pharmaceutically acceptable salt thereof;   (b) 5-10% Microcrystalline cellulose;   (c) up to 5% Povidone;   (d) up to 1% Magnesium stearate;   (e) 5-10% Lactose; and   (f) 5-10% Croscarmellose sodium.   
     
     
         45 . A composition as claimed in  claim 1 , wherein an analgesic-containing immediate release portion comprises:
 (a) 70-75% Naproxen or a pharmaceutically acceptable salt thereof;   (b) 5-10% Microcrystalline cellulose;   (c) up to 5% Povidone;   (d) up to 1% Magnesium stearate;   (e) up to 5% Lactose; and   (f) 15-20% Sodium Lauryl Sulphate.   
     
     
         46 . A composition as claimed in  claim 1 , wherein an analgesic-containing immediate release portion comprises:
 (a) 70-75% Naproxen or a pharmaceutically acceptable salt thereof;   (b) 5-10% Microcrystalline cellulose;   (c) up to 5% Povidone;   (d) up to 1% Magnesium stearate;   (e) up to 2% Croscarmellose sodium; and   (f) 15-20% Sodium Lauryl Sulphate.   
     
     
         47 . A composition as claimed in  claim 1 , wherein a guaifenesin-containing immediate release portion comprises:
 (a) 30-40% Guaifenesin;   (b) up to 5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 50-60% Microcrystalline cellulose;   (d) up to 7% Povidone;   (e) up to 7% Croscarmellose sodium; and   (f) up to 1% Magnesium stearate.   
     
     
         48 . A composition as claimed in  claim 1 , wherein a guaifenesin-containing immediate release portion comprises:
 (a) 40-50% Guaifenesin;   (b) up to 5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 40-50% Microcrystalline cellulose;   (d) up to 5% Hypromellose;   (e) up to 5% Sodium starch glycolate; and   (f) up to 1% Magnesium stearate.   
     
     
         49 . A composition as claimed in  claim 1 , wherein a guaifenesin-containing immediate release portion comprises:
 (a) 50-65% Guaifenesin;   (b) up to 5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 25-40% Microcrystalline cellulose;   (d) up to 5% Povidone;   (e) up to 5% Croscarmellose sodium; and   (f) up to 1% Magnesium stearate.   
     
     
         50 . A composition as claimed in  claim 1 , wherein a modified release portion comprises:
 (a) 80-90% Guaifenesin;   (b) up to 5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) up to 10% Hypromellose;   (d) up to 5% Carbomer; and   (e) up to 1.55% Magnesium stearate.   
     
     
         51 . A composition as claimed in  claim 1 , wherein a modified release portion comprises:
 (a) 80-90% Guaifenesin;   (b) 3-6% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) up to 5% Hypromellose;   (d) up to 2% Hydroxy ethylcellulose;   (e) up to 5% Microcrystalline cellulose; and   (f) up to 1% Magnesium stearate.   
     
     
         52 . A composition as claimed in  claim 1 , wherein a modified release portion comprises:
 (a) 80-90% Guaifenesin;   (b) 3-6% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) up to 5% Hypromellose;   (d) up to 5% Hydroxy ethylcellulose;   (e) up to 5% Microcrystalline cellulose; and   (f) up to 1% Magnesium stearate.   
     
     
         53 . A composition as claimed in  claim 1 , wherein a modified release portion comprises:
 (a) 85-90% Guaifenesin;   (b) 4-5% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 3-6% Hypromellose;   (d) 1-3% Carbomer; and   (e) 0.5-1% Magnesium stearate.   
     
     
         54 . A composition as claimed in  claim 1 , wherein a modified release portion comprises:
 (a) 90-93% Guaifenesin;   (b) 4-6% Dextromethorphan or a pharmaceutically acceptable salt thereof;   (c) 1-3% Carbomer; and   (d) 0.5-1% Magnesium stearate.