Absorption enhancers for drug administration

Abstract

A composition including a surfactant and at least one alkyl glycoside and/or saccharide alkyl ester and a drug. The surfactant composition(s) when admixed with a drug is non-toxic and non-irritating, while stabilizing and increasing the bioavailability of the drug. The invention also provides compositions that enhance absorption of drugs via the oral, ocular, nasal, nasolacrimal, inhalation or pulmonary, oral cavity (sublingual or Buccal cell) or CSF delivery route of a patient, including but not limited to insulin, glucagon and exendin-4.

1 . A surfactant composition comprising of at least one alkyl glycoside and/or at least one saccharide alkyl ester, and when admixed with a drug, the surfactant stabilizes the biological activity and increases the bioavailability, of the drug.  
   
   
       2 . The composition of  claim 1 , wherein the drug is a peptide or a protein.  
   
   
       3 . The composition of  claim 1 , wherein the surfactant has a high no observable adverse effect level.  
   
   
       4 . The composition of  claim 1 , wherein the surfactant has a high no observable adverse effect level at least 10 times higher than the daily intake amount of the surfactant.  
   
   
       5 . The composition of  claim 1 , wherein the surfactant has a high no observable adverse effect level at least 100 times higher than the daily intake amount of the surfactant.  
   
   
       6 . The composition of  claim 1 , wherein the surfactant has a high no observable adverse effect level at least 1000 times higher than the daily intake amount of the surfactant.  
   
   
       7 . The composition of  claim 1 , wherein the surfactant is a physiological non-irritant.  
   
   
       8 . The composition of  claim 1 , wherein the surfactant has from about 10 to 16 carbon atoms.  
   
   
       9 . The composition of  claim 1 , wherein the surfactant and the drug are administered to subjects.  
   
   
       10 . The composition of  claim 1 , wherein the surfactant and the drug are administered to humans.  
   
   
       11 . The composition of  claim 1 , wherein the surfactant has anti-bacterial activity.  
   
   
       12 . The composition of  claim 1 , wherein the surfactant and the drug do not enter the hepatic portal blood system.  
   
   
       13 . The composition of  claim 1 , wherein the surfactant is stable for at least six months from about 4° C. to 25° C.  
   
   
       14 . The composition of  claim 1 , wherein the surfactant concentration is from about 0.01% to 20%.  
   
   
       15 . The composition of  claim 1 , wherein the surfactant concentration is from about 0.01% to 5%.  
   
   
       16 . The composition of  claim 1 , wherein the surfactant concentration is from about 0.01% to 2%.  
   
   
       17 . A therapeutic composition comprising of at least one biologically active compound(s) and at least one surfactant, wherein the surfactant is further comprised of at least one alkyl glycoside and/or saccharide alkyl ester and wherein said composition stabilizes the biological activity of the drug, for at least about 6 months from about 4° C. to 25° C.  
   
   
       18 . The composition of  claim 17 , wherein the pH of the composition is less than 8.0.  
   
   
       19 . The composition of  claim 17 , wherein the composition is stable for at least six months from about 4° C. to 25° C.  
   
   
       20 . The composition of  claim 17 , wherein the composition concentration is from about 0.01% to 20%.  
   
   
       21 . The composition of  claim 17 , wherein the composition concentration is from about 0.01% to 5%.  
   
   
       22 . The composition of  claim 17 , wherein the composition concentration is from about 0.01% to 2%.  
   
   
       23 . A stable therapeutic composition according to  claim 17 , wherein the composition is formulated for mucosal administration to a subject.  
   
   
       24 . A stable therapeutic composition according to  claim 17 , wherein the administration to the subject yields enhanced mucosal delivery of said biologically active compound(s) comprising: 
 a) a peak concentration (C max ) of said biologically active compound(s) in a CNS tissue or fluid or in a blood plasma of said subject that is about 15% or greater as compared to a peak concentration of the biologically active compounds in CNS or blood plasma following intramuscular injection of an equivalent concentration of the biologically active compound(s) to the subject;    b) an area under concentration curve (AUC) of the biologically active compound(s) in the central nervous system (CNS) tissue or fluid or in the blood plasma of the subject that is 20% or greater compared to an AUC of biologically active compound(s) in CNS or blood plasma following intramuscular injection of an equivalent concentration of the biologically active compound(s) to said subject; or c) a time to maximal concentration (t max ) of the biologically active compound(s) in a central nervous system (CNS) tissue or fluid or in the blood plasma of the subject between about 0.1 to 1.0 hours.    
   
   
       25 . The therapeutic composition of  claim 17 , wherein the composition following mucosal administration to the subject yields a peak concentration (C max ) of the biologically active compound(s) in the CNS tissue or fluid or in a blood plasma of the subject that is 20% or greater as compared to a peak concentration of the biologically active compound(s) in the CNS tissue or fluid or blood plasma following intramuscular injection of an equivalent concentration of the biologically active compound(s) to the subject.  
   
   
       26 . The therapeutic composition of  claim 17 , wherein the composition following mucosal administration to the subject yields a peak concentration (C max ) of the biologically active compound(s) in the CNS tissue or fluid or in the blood plasma of the subject that is 50% or greater as compared to a peak concentration of the biologically active compound(s) in the CNS or blood plasma following intramuscular injection of an equivalent concentration or dose of said biologically active compound(s) to the subject.  
   
   
       27 . The therapeutic composition of  claim 17 , wherein said composition following mucosal administration to said subject yields an area under concentration curve (AUC) of said biologically active compound(s) in said CNS tissue or fluid or in a blood plasma of the subject that is 20% or greater compared to an AUC of said biologically active compound(s) in said CNS or blood plasma following intramuscular injection of an equivalent concentration or dose of said biologically active compound(s) to said subject.  
   
   
       28 . The therapeutic composition of  claim 17 , wherein the composition following mucosal administration to the subject yields an area under concentration curve (AUC) of said biologically active compound(s) in the CNS tissue or fluid or in the blood plasma of the subject that is 50% or greater compared to an AUC of the biologically active compound(s) in said CNS or blood plasma following intramuscular injection of an equivalent concentration of the biologically active compound(s) to the subject.  
   
   
       29 . The pharmaceutical composition of  claim 17 , wherein the composition following mucosal administration to the subject yields a time to maximal plasma concentration (t max ) of the biologically active compound(s) in the CNS tissue or fluid or in the blood plasma of the subject between about 0.1 to 1.0 hours.  
   
   
       30 . The pharmaceutical composition of  claim 17 , wherein the composition following mucosal administration to the subject yields a time to maximal plasma concentration (t max ) of the biologically active compound(s) in the CNS tissue or fluid or in the blood plasma of the subject between about 0.2 to 0.5 hours.  
   
   
       31 . A method of administering a drug composition comprising of a surfactant having at least one alkyl glycoside and/or saccharide alkyl ester mixed with at least one drug and delivered to a subject, wherein the alkyl has from about 10 to 24 carbon atoms, and the surfactant increases the stability and bioavailability of the drug.  
   
   
       32 . The method of  claim 31 , wherein the surfactant has a high no observable adverse effect level.  
   
   
       33 . The method of  claim 31 , wherein the surfactant has a high no observable adverse effect level 10 times higher than the daily intake amount of the surfactant.  
   
   
       34 . The method of  claim 31 , wherein the surfactant has a high no observable adverse effect level 100 times higher than the daily intake amount of the surfactant.  
   
   
       35 . The method of  claim 31 , wherein the surfactant has a high no observable adverse effect level 1000 times higher than the daily intake amount of the surfactant.  
   
   
       36 . The method of  claim 31 , wherein the surfactant reduces the bioavailability variance from patient to patient.  
   
   
       37 . The method of  claim 31 , wherein the composition does not enter the hepatic portal blood system.  
   
   
       38 . The method of  claim 31 , wherein the pH of the composition is less than 8.0.  
   
   
       39 . The method of  claim 31 , wherein the composition is stable for at least six months from about 4° C. to 25° C.  
   
   
       40 . The method of  claim 31 , wherein the composition concentration is from about 0.01% to 20%.  
   
   
       41 . The method of  claim 31 , wherein the composition concentration is from about 0.01% to 5%.  
   
   
       42 . The method of  claim 31 , wherein the composition concentration is from about 0.01% to 2%.  
   
   
       43 . The method of  claim 31  wherein the composition is administered to the mucosal membranes or tissue of a subject.  
   
   
       44 . The method of  claim 1 , wherein the composition is further comprised of an enteric coating.  
   
   
       45 . The method of  claim 1 , wherein the alkyl glycoside is tetradecylmaltoside (TDM).  
   
   
       46 . The method of  claim 45 , wherein the TDM has anti-bacterial activity.  
   
   
       47  to  138 . (canceled)