Chemically stable compositions of a pharmaceutical active agent in a multi-chambered delivery system for mucosal delivery

Abstract

A kit for mucosally administering a metastable supersaturated solution of a pharmaceutical active agent to a human patient includes a first compartment comprising a first composition comprising a pharmaceutical active agent in solution at or below equilibrium solubility, and a second composition comprising an acidic buffer. The first and second compartments maintain separation of the first and second compositions during storage, and allow for mixing of the first and second compositions to form a supersaturated solution above equilibrium solubility of the pharmaceutical active agent for immediate mucosal administration to a human patient. In one embodiment, the second composition comprises an acidic buffer and the supersaturated solution has an acidic pH. Alternatively, the second composition comprises a basic buffer and the supersaturated solution has a basic pH.

What is claimed is: 
     
         1 . A method for administering a mucosally absorbable gel composition to a human patient, comprising:
 providing a first compartment comprising a first composition containing a substantially water-soluble pharmaceutical active agent in a solution together with one or more optional suitable pharmaceutical excipients; and a second compartment comprising a second composition with one or more optional suitable pharmaceutical excipients, at least one of the first and second compositions containing an effective amount of a crystallization inhibitor; wherein the first and second compartments maintain separation of the first and second compositions during storage and allow for mixing of the first and second compositions to form a mucosally absorbable gel composition for immediate mucosal administration to a human patient, wherein the second composition in the second compartment is at a basic pH and contains an alkaline buffer and the mucosally absorbable gel composition has a pH >7;   mixing the first and second compositions to provide a mixed composition containing the pharmaceutical active agent in a state of supersaturation; and then   administering the mixed composition to a buccal, sublingual, intranasal, vaginal or rectal mucosal site of the human patient.   
     
     
         2 . The method according to  claim 1 , wherein, after mixing, the mixed composition contains the pharmaceutical active agent in the state of supersaturation for >10 minutes. 
     
     
         3 . The method according to  claim 1 , wherein the mixed composition is administered to an intranasal site of the human patient. 
     
     
         4 . The method according to  claim 1 , wherein the mixed composition comprises an effective amount of a crystallization inhibitor. 
     
     
         5 . A method for administering a mucosally absorbable gel composition to a human patient, comprising a first compartment comprising a first composition containing a substantially water-soluble pharmaceutical active agent in a solution together with one or more optional suitable pharmaceutical excipients; and a second compartment comprising a second composition with one or more optional suitable pharmaceutical excipients, at least one of the first and second compositions containing an effective amount of a crystallization inhibitor; wherein the first and second compartments maintain separation of the first and second compositions during storage and allow for mixing of the first and second compositions to form a mucosally absorbable gel composition for immediate mucosal administration to a human patient, wherein the second composition in the second compartment is at an acidic pH and contains an acidic buffer and the mucosally absorbable gel composition has a pH <6;
 mixing the first and second compositions to provide a mixed composition containing the pharmaceutical active agent in a state of supersaturation; and then   administering the mixed composition to a buccal, sublingual, intranasal, vaginal or rectal mucosal site of the human patient.   
     
     
         6 . The method according to  claim 5 , wherein, after mixing, the mixed composition contains the pharmaceutical active agent in the state of supersaturation for >10 minutes. 
     
     
         7 . The method according to  claim 5 , wherein the mixed composition is administered to an intranasal site of the human patient. 
     
     
         8 . The method according to  claim 5 , wherein the mixed composition comprises an effective amount of a crystallization inhibitor. 
     
     
         9 . A method of administering a mucosally absorbable gel composition to a human patient, comprising a first compartment comprising a first composition comprising a pharmaceutical active agent that is substantially lipid soluble and substantially water insoluble, in a substantially non-aqueous solution; and a second compartment comprising a second composition comprising a substantially aqueous solution; wherein the first and second compartments maintain separation of the first and second compositions during storage, and allow for mixing of the first and second compositions to form a mixed mucosally absorbable gel composition for immediate mucosal administration to a human patient, and wherein the second composition of the second compartment has an acidic pH and said mixed mucosally absorbable gel composition has an acidic pH or wherein the second composition of the second compartment contains a basic buffer and said mixed mucosally absorbable composition has a basic pH;
 mixing the first and second compositions to provide a mixed composition containing the pharmaceutical active agent in a state of supersaturated microemulsion; and then   administering the mixed composition to a buccal, sublingual, intranasal, vaginal or rectal mucosal site of the human patient.   
     
     
         10 . The method according to  claim 9 , wherein the mixed composition is administered to an intranasal site of the human patient. 
     
     
         11 . The method according to  claim 9 , wherein the mixed composition comprises an effective amount of a crystallization inhibitor.