Immediate release oral guaifenesin solution
View Patent ↗Disclosed is an immediate release solution for oral administration of guaifenesin and at least one additional drug. In addition to water the solution comprises as solvents propylene glycol and glycerol in a concentration which significantly increases the bioavailability of guaifenesin in the human body.
1. An immediate release solution for oral administration of guaifenesin and one or more additional drugs, wherein the one or more additional drugs comprise at least one of an antitussive, a decongestant, an antihistamine or an analgesic and the solution comprises as solvents water and a total of from 48% to 72% by weight, relative to a total weight of the solution, of propylene glycol and glycerol, and wherein the solution, when orally administered to an adult human subject as a single dose in an amount which affords 200 mg of guaifenesin, provides (i) a C max of at least 3600 ng/mL of guaifenesin and/or an AUC (0-inf) of guaifenesin of at least 3700 ng·hr/mL and (ii) a therapeutically effective plasma concentration of guaifenesin for at least 4 hours.
2. The solution of claim 1 , wherein the solution comprises a total of from 54% to 66% by weight of propylene glycol and glycerol.
3. The solution of claim 1 , wherein a weight ratio of glycerol to propylene glycol is from 1.7:1 to 2.5:1.
4. The solution of claim 1 , wherein the solution comprises from 15% to 23% by of propylene glycol.
5. The solution of claim 1 , wherein the solution comprises from 33% to 49% by weight of glycerol.
6. The solution of claim 1 , wherein the solution provides a C max of at least 3800 ng/mL of guaifenesin.
7. The solution of claim 1 , wherein the solution provides a C max of at least 4000 ng/mL of guaifenesin.
8. The solution of claim 6 , wherein the solution provides an AUC (0-inf) of guaifenesin of at least 3900 ng·hr/mL.
9. The solution of claim 7 , wherein the solution further provides an AUC (0-inf) of guaifenesin of at least 4100 ng·hr/mL.
10. The solution of claim 1 , wherein the one or more additional drugs comprise a decongestant.
11. The solution of claim 10 , wherein the decongestant comprises at least one of pseudoephedrine and a pharmaceutically acceptable salt thereof.
12. The solution of claim 10 , wherein the decongestant comprises at least one of phenylephrine and a pharmaceutically acceptable salt thereof.
13. The solution of claim 1 , wherein the one or ore additional drugs comprise an antihistamine.
14. The solution of claim 13 , wherein the antihistamine comprises at least one of brompheniramine, chlorcyclizine, chlorpheniramine, dexbrompheniramine, dexchlorpheniramine, diphenhydramine, doxylamine, phenindamine, pheniramine, pyrilamine, thonzylamine, triprolidine, and/or a pharmaceutically acceptable salt of any of these drugs.
15. The solution of claim 1 , wherein the one or more additional drugs comprise an analgesic.
16. An immediate release solution for oral administration of guaifenesin and one or more additional drugs, wherein the one or more additional drugs comprise at least one of an antitussive, a decongestant, an antihistamine or an analgesic and the solution comprises as solvents water and additionally propylene glycol and glycerol in a concentration which, when orally administered to an adult human subject as a single dose in an amount which affords 200 mg of guaifenesin, provides in (i) a C max of guaifenesin which is higher than the C max of guaifenesin provided by an aqueous solution without propylene glycol and glycerol that comprises the same concentrations of guaifenesin and the at least one additional drug by a factor of at least 1.5 and/or an AUC (0-inf) of guaifenesin which is higher than the AUC (0-inf) of guaifenesin provided by the aqueous solution by a factor of at least 1.4 and (ii) a therapeutically effective plasma concentration of guaifenesin for at least 4 hours.
17. The solution of claim 16 , wherein the solution provides a C max of guaifenesin which is higher than the C max of guaifenesin provided by an aqueous solution by a factor of at least 1.6 and an AUC (0-inf) of guaifenesin which is higher than the AUC (0-inf) of guaifenesin provided by the aqueous solution by a factor of at least 1.5.
18. The solution of claim 17 , wherein the solution comprises a total of from 48% to 72% by weight of propylene glycol and glycerol, based on a total weight of the solution.
19. The solution of claim 16 , wherein the one or more additional drugs comprise a decongestant.
20. The solution of claim 16 , wherein the one or more additional drugs comprise an antihistamine.