Delivery of Drugs to Mucosal Surfaces

Abstract

Liquid pharmaceutical compositions for administration to a mucosal surface, including a therapeutic agent and a pectin with a low degree of esterification are described. Such compositions gel, or can be adapted to gel, at the site of application in the absence of an extraneous source of divalent metal ions.

1 . A sprayable liquid pharmaceutical composition for administration to the mucosa of the nasal cavity consisting essentially of:
 a drug,   a pectin that has a degree of esterification that is about 10% to less than 50%, and   an aqueous carrier, wherein the composition gels only upon administration to a mucosal surface of the nasal cavity and in the absence of divalent metal ions in the composition or delivered simultaneously or sequentially with the composition.   
     
     
         2 . The composition of  claim 1 , wherein the drug acts locally at the mucosa of the nasal cavity. 
     
     
         3 . The composition of  claim 2 , wherein the drug is selected from the group consisting of a steroid, an antiviral agent, a decongestant, an anti-allergic agent, an antihistamine, an antifungal agent and an anti-bacterial agent. 
     
     
         4 . The composition of  claim 2 , wherein the drug is a gene. 
     
     
         5 . The composition of  claim 2 , wherein the drug is selected from the group consisting of a vaccine, an antibody, and a prophylactic agent against HIV. 
     
     
         6 . The composition of  claim 2 , wherein the drug is selected from fluticasone, pirovadir ICAM-1, acyclovir, bromovinyldeoxyuridine, α-interferon, β-interferon, γ-interferon, zidovudine, oxymetazoline, sodium cromoglycate, budesonide, diphenhydramine hydrochloride, amphotericin, nystatin, a vaccine against influenza, a vaccine against pertussis, a vaccine against measles, a vaccine against diphtheria, a deoxyribonucleic acid vaccine, an antibody against respiratory syncytial virus and fexofenadine. 
     
     
         7 . The composition of  claim 1 , wherein the drug acts systemically. 
     
     
         8 . The composition of  claim 7 , wherein the drug is selected from the group consisting of nicotine, hyoscine hydrobromide, lignocaine, naratriptan, a pheromone and propranolol. 
     
     
         9 . The composition of  claim 7 , wherein the drug is apomorphine. 
     
     
         10 . The composition of  claim 7 , wherein the drug is fentanyl. 
     
     
         11 . The composition of  claim 1 , wherein the pectin has a degree of esterification that is about 10% to less than 35%. 
     
     
         12 . The composition of  claim 1 , wherein the composition is in a form selected from the group consisting of a free flowing system and a spray. 
     
     
         13 . The composition of  claim 1 , wherein the composition has a pH of 2 to 9. 
     
     
         14 . The composition of  claim 1 , wherein the pectin is present in a concentration of 1 g/L to 100 g/L. 
     
     
         15 . The composition of  claim 1 , wherein the pectin is present in a concentration of 1 g/L to 50 g/L. 
     
     
         16 . A pharmaceutical gel composition prepared and that exists only in gel form by applying the sprayable liquid composition according to  claim 1  to the mucosal surface of the mucosa of the nasal cavity of a mammal in the absence of divalent metal ions in the composition or delivered with the composition. 
     
     
         17 . The pharmaceutical gel composition of  claim 16 , wherein the pectin has a degree of esterification of about 10% to less than 35%. 
     
     
         18 . A kit comprising a composition for administration to the mucosa of the nasal cavity of a mammal, the composition consisting essentially of a drug, a pectin that has a degree of esterification of about 10% to less than 50%, and an aqueous carrier which gels at the mucosa of the nasal cavity of the mammal in the absence of divalent metal ions in the composition or delivered with the composition, but the kit does not include a solution of divalent metal ions. 
     
     
         19 . The kit of  claim 18 , wherein the drug is a drug that acts locally at the mucosa of the nasal cavity and is selected from the group consisting of a steroid, an anti-viral agent, a decongestant, an anti-allergic agent, an antihistamine, an anti-fungal agent, an antibacterial agent, a gene, a vaccine, an antibody, a prophylactic agent against HIV, fluticasone, ICAM-1, pirovadir, acyclovir, bromovinyldeoxyuridine, α-interferon, β-interferon, γ-interferon, zidovudine, oxymetazoline, sodium cromoglycate, budesonide, diphenhydramine hydrochloride, amphotericin, nystatic, a vaccine against influenza, a vaccine against pertussis, a vaccine against measles, and a vaccine against diphtheria, a deoxyribonucleic acid vaccine, an antibody against respiratory synctial virus and fexofenadine. 
     
     
         20 . The kit of  claim 18 , wherein the pectin has a degree of esterification that is about 10% to less than 35%. 
     
     
         21 . The kit of  claim 18 , wherein the composition is in a form selected from the group consisting of a free flowing system and a spray. 
     
     
         22 . The kit of  claim 18 , wherein the composition has a pH of 2 to 9. 
     
     
         23 . The kit of  claim 18 , wherein the pectin is present in the composition in a concentration of 1 g/L to 100 g/L. 
     
     
         24 . The kit of  claim 18 , wherein the pectin is present in the composition in a concentration of 1 g/L to 50 g/L. 
     
     
         25 . The kit of  claim 18 , wherein the drug is a drug that acts systemically and is selected from the group consisting of nicotine, hyoscine hydrobromide, lignocaine, naratriptan, a pheromone, and propranolol. 
     
     
         26 . The kit of  claim 18 , wherein the drug is a drug that acts systemically and is apomorphine. 
     
     
         27 . The kit of  claim 18 , wherein the drug is a drug that acts systemically and is fentanyl. 
     
     
         28 . A method of delivering a drug to a mucosal surface in a mammal comprising administering a sprayable liquid pharmaceutical composition to the mucosal surface, wherein the composition consists essentially of a drug, a pectin consisting essentially of a pectin that has a degree of esterification of about 10% to less than 50%, and an aqueous carrier, and the drug is a drug that acts systemically, and wherein the composition gels only upon administration to the mucosal surface in the absence of divalent metal ions in or delivered with the composition.