Gaba analog prodrug sustained release oral dosage forms

Abstract

Sustained release oral dosage forms of a gabapentin prodrug, 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid, are disclosed. The dosage forms are useful for treating or preventing diseases and disorders for which gabapentin is therapeutically effective.

1 - 35 . (canceled) 
     
     
         36 . A method of treating hot flashes in a patient, comprising administering to the patient in need of such treatment one or more sustained release oral tablets comprising:
 (a) 10 wt % to 65 wt % of 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid;   (b) 30 wt % to 50 wt % dibasic calcium phosphate;   (c) 1 wt % to 50% of a release rate-modifying polymer;   wherein wt % is based on the total dry weight of the dosage form, which one or more tablets:   when administered to one or more fasted human patients in need of a method of treating hot flashes at a dose of 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid ranging from about 1100 mg to about 1300 mg provides a gabapentin plasma concentration profile characterized by a C max  ranging from about 3 μg/mL to about 6 μg/mL, a T max  ranging from about 4 hours to about 7 hours, and a AUC ranging from about 30 μg·hr/mL to about 70 μg·hr/mL; or   when administered to one or more fed human patients in need of a method of treating hot flashes at a dose of 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid ranging from about 1100 mg to about 1300 mg provides a gabapentin plasma concentration profile characterized by a C max  ranging from about 5 μg/mL to about 8 μg/mL, a T max  ranging from about 6 hours to about 11 hours, and a AUC ranging from about 60 μg·hr/mL to about 110 μg·hr/mL.   
     
     
         37 . The method of  claim 36 , the tablet comprising an amount of 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid ranging from 300 mg to 700 mg. 
     
     
         38 . The method of  claim 36 , wherein the release-rate modifying polymer is selected from a fatty compound and a methacrylic acid copolymer. 
     
     
         39 . The method of  claim 38 , wherein the fatty compound is a glyceryl ester. 
     
     
         40 . The method of  claim 38 , wherein the glyceryl ester is selected from glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, lauroyl macorgol glycerice, stearoyl macrogol glyceride, and a combination of any of the foregoing. 
     
     
         41 . The method of  claim 40 , wherein the glyceryl ester is glyceryl behenate. 
     
     
         42 . The method of  claim 36 , wherein the 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid is in a crystalline form. 
     
     
         43 . The method of  claim 36 , wherein each said tablet comprises one or more pharmaceutically acceptable excipients selected from diluents, lubricants, anti-adherents, glidiants, surfactants, disintegrants, and combinations of any of the foregoing. 
     
     
         44 . The method of  claim 43 , wherein the diluent is microcrystalline cellulose. 
     
     
         45 . The method of  claim 36 , wherein the dosing comprises frequency of twice per day. 
     
     
         46 . A method of treating hot flashes in a patient, comprising administering to the patient in need of such treatment one or more sustained release oral tablets comprising:
 (a) 10 wt % to 65 wt % of 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid;   (b) 30 wt % to 50 wt % dibasic calcium phosphate;   (c) 1 wt % to 50% of a release rate-modifying polymer;   wherein wt % is based on the total dry weight of the dosage form, which tablet, when placed in 10 mM monobasic potassium phosphate buffer and 1% (wt/volume) sodium lauryl sulfate at pH 7.4 and 37° C. and agitated at 50 rpm (USP, Type II), releases 20% of the 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid after 2 hours, 50% after 5 hours and 80% after 8 hours.   
     
     
         47 . The method of  claim 46 , the tablet comprising an amount of 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid ranging from 300 mg to 700 mg. 
     
     
         48 . The method of  claim 46 , wherein the 1-{[α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid is in a crystalline form. 
     
     
         49 . The method of  claim 46 , wherein each said tablet comprises one or more pharmaceutically acceptable excipients selected from diluents, lubricants, anti-adherents, glidiants, surfactants, disintegrants, and combinations of any of the foregoing. 
     
     
         50 . The method of  claim 46 , wherein the dosing comprises frequency of twice per day.