Transnasal Anticonvulsive Pharmaceutical Composition Comprising Poorly Soluble Anticonvulsant

Abstract

There is provided a transnasal anticonvulsive pharmaceutical composition including a poorly soluble anticonvulsant. The anticonvulsive pharmaceutical composition comprising a poorly soluble anticonvulsant as an active component, which is transnasally spray-administered, comprises diethylene glycol monoethyl ether and fatty acid ester, wherein the fatty acid ester is selected from the group consisting of caprylocaproyl polyoxylglyceride, isopropyl palmitate, oleoyl polyoxylglyceride, sorbitan monolaurate 20, methyl laurate, ethyl laurate and polysorbate 20. Also, the anticonvulsive pharmaceutical composition comprising a poorly soluble anticonvulsant as an active component, which is transnasally spray-administered, comprises diethylene glycol monoethyl ether, fatty acid ester, methylpyrrolidone, water and alcohol. Therefore, the transnasal anticonvulsive pharmaceutical composition may be useful to highly enhance the bioavailability of the poorly soluble anticonvulsant. Also, the transnasal anticonvulsive pharmaceutical composition may be useful to allow the poorly soluble anticonvulsant to show the improved viscosity and/or enhanced solubility in order to effectively deliver the poorly soluble anticonvulsant at a therapeutic dose.

1 . An anticonvulsive pharmaceutical composition comprising a poorly soluble anti-convulsant as an active component, which is transnasally spray-administered, comprising diethylene glycol monoethyl ether and fatty acid ester, wherein the fatty acid ester is selected from the group consisting of caprylocaproyl polyoxyl-glyceride, isopropyl palmitate, oleoyl polyoxylglyceride, sorbitan monolaurate 20, methyl laurate, ethyl laurate, and polysorbate 20. 
     
     
         2 . The anticonvulsive pharmaceutical composition of  claim 1 , wherein the poorly soluble anticonvulsant is at least one selected from the group consisting of diazepam and lorazepam. 
     
     
         3 . The anticonvulsive pharmaceutical composition of  claim 2 , wherein the poorly soluble anticonvulsant is present in a content of 1 to 20% by weight, based on the total weight of the pharmaceutical composition. 
     
     
         4 . The anticonvulsive pharmaceutical composition of  claim 1 , wherein the fatty acid ester is present in a content of at least 30% by weight, based on the total weight of the pharmaceutical composition. 
     
     
         5 . A pharmaceutical composition, comprising 5 to 20% by weight of at least one poorly soluble anticonvulsant selected from the group consisting of diazepam and lorazepam, 40 to 60% by weight of diethylene glycol monoethyl ether, and 35 to 50% by weight of fatty acid ester, wherein the fatty acid ester is selected from the group consisting of caprylocaproyl polyoxylglyceride, isopropyl palmitate, oleoyl polyoxylglyceride, sorbitan monolaurate 20, methyl laurate, ethyl laurate, and polysorbate 20. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the fatty acid ester is at least one selected from the group consisting of caprylocaproyl polyoxylglyceride, isopropyl palmitate, oleoyl polyoxylglyceride, sorbitan monolaurate 20, and polysorbate 20. 
     
     
         7 . An anticonvulsive pharmaceutical composition comprising a poorly soluble anti-convulsant as an active component, which is transnasally spray-administered, comprising diethylene glycol monoethyl ether, fatty acid ester, methylpyrrolidone, water and alcohol. 
     
     
         8 . The anticonvulsive pharmaceutical composition of  claim 7 , wherein the poorly soluble anticonvulsant is at least one selected from the group consisting of diazepam and lorazepam. 
     
     
         9 . The anticonvulsive pharmaceutical composition of  claim 7 , wherein the fatty acid ester is selected from the group consisting of caprylocaproyl polyoxyl-glyceride, isopropyl palmitate, oleoyl polyoxylglyceride, sorbitan monolaurate 20, methyl laurate, ethyl laurate, polysorbate 20 and propylene glycol mono-caprylate. 
     
     
         10 . The anticonvulsive pharmaceutical composition of  claim 9 , wherein the fatty acid ester comprises methyl laurate. 
     
     
         11 . The anticonvulsive pharmaceutical composition of  claim 7 , wherein the alcohol is ethanol. 
     
     
         12 . The anticonvulsive pharmaceutical composition of  claim 7 , wherein the poorly soluble anticonvulsant is present in a content of 1 to 20% by weight, based on the total weight of the pharmaceutical composition. 
     
     
         13 . The anticonvulsive pharmaceutical composition of  claim 7 , wherein the pharmaceutical composition has kinetic viscosity of 10 mm 2 /sec or less for the transnasal spray-administration. 
     
     
         14 . The anticonvulsive pharmaceutical composition of  claim 7 , wherein the fatty acid ester is present in a content of at least 30% by weight, based on the total weight of the pharmaceutical composition. 
     
     
         15 . The anticonvulsive pharmaceutical composition of  claim 7 , comprising 5 to 20% by weight of at least one poorly soluble anticonvulsant selected from the group consisting of diazepam and lorazepam, 40 to 60% by weight of diethylene glycol monoethyl ether, 5 to 15% by weight of methyl laurate, 5 to 30% by weight of methylpyrrolidone, 1 to 5% by weight of water, and 5 to 10% by weight of ethanol. 
     
     
         16 . The anticonvulsive pharmaceutical composition of  claim 7 , further comprising dimethyl isosorbide. 
     
     
         17 . The anticonvulsive pharmaceutical composition of  claim 16 , wherein the dimethyl isosorbide is present in a content of 5 to 10% by weight, based on the total weight of the pharmaceutical composition. 
     
     
         18 . A method for treating convulsions, comprising:
 transnasally spray-administering to patients suffering from the convulsions a sufficient amount of the pharmaceutical composition defined in  claim 1  to treat the convulsions.