Pharmaceutical composition of doxycycline with reduced food effect

Abstract

The present invention relates to a once daily tablet comprising doxycycline at sub-antibiotic dose and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect. The invention further provides a method of treatment of rosacea by administering to a person in need thereof the doxycycline tablet with or without food. A process of preparing the tablet is also provided.

We claim: 
     
         1 . A low dose once daily tablet comprising doxycycline at a sub-antibiotic dose and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect. 
     
     
         2 . The low dose once daily tablet according to  claim 1 , wherein the sub-antibiotic dose of doxycycline is in the range of 24 mg to 36 mg. 
     
     
         3 . The low dose once daily tablet according to  claim 1 , wherein the sub-antibiotic dose of doxycycline is 30 mg. 
     
     
         4 . The low dose once daily tablet according to  claim 1 , wherein the sub-antibiotic dose of doxycycline is 32 mg. 
     
     
         5 . The low dose once daily tablet according to  claim 1 , wherein the sub-antibiotic dose of doxycycline is 34 mg. 
     
     
         6 . The low dose once daily tablet according to  claim 1 , wherein the sub-antibiotic dose of doxycycline is 36 mg. 
     
     
         7 . The low dose once daily tablet according to  claim 1 , wherein the dose of doxycycline is reduced by 10% in comparison to the marketed Oracea® capsules containing 40 mg of doxycycline. 
     
     
         8 . The low dose once daily tablet according to  claim 1 , wherein the dose of doxycycline is reduced by 15% in comparison to the marketed Oracea® capsules containing 40 mg of doxycycline. 
     
     
         9 . The low dose once daily tablet according to  claim 1 , wherein the dose of doxycycline is reduced by 20% in comparison to the marketed Oracea® capsules containing 40 mg of doxycycline. 
     
     
         10 . The low dose once daily tablet according to  claim 1 , wherein the dose of doxycycline is reduced by 30% in comparison to the marketed Oracea® capsules containing 40 mg of doxycycline. 
     
     
         11 . The low dose once daily tablet according to  claim 1 , wherein the dose of doxycycline is reduced by 40% in comparison to the marketed Oracea® capsules containing 40 mg of doxycycline. 
     
     
         12 . The low dose once daily tablet according to  claim 1 , wherein the tablet exhibits a reduced food effect such that the food effect on C max  is less than 40%, and the food effect on AUC 0-t  is less than 20% compared to when the tablet is administered in a fasted state. 
     
     
         13 . The low dose once daily tablet according to  claim 1 , wherein the low dose once daily tablet comprises (i) 50% to 99% of doxycycline and one or more pharmaceutically acceptable excipients as an immediate-release portion; and (ii) 1% to 50% of doxycycline, a controlled-release polymer, and one or more pharmaceutically acceptable excipients as a controlled-release portion, wherein the once daily tablet provides a total daily dosage of 24 mg to 36 mg when administered once daily. 
     
     
         14 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 94% of doxycycline and the controlled-release portion contains 6% of doxycycline. 
     
     
         15 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 93% of doxycycline and the controlled-release portion contains 7% of doxycycline. 
     
     
         16 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 89% of doxycycline and the controlled-release portion contains 11% of doxycycline. 
     
     
         17 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 88% of doxycycline and the controlled-release portion contains 12% of doxycycline. 
     
     
         18 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 87% of doxycycline and the controlled-release portion contains 13% of doxycycline. 
     
     
         19 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 85% of doxycycline and the controlled-release portion contains 15% of doxycycline. 
     
     
         20 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 83% of doxycycline and the controlled-release portion contains 17% of doxycycline. 
     
     
         21 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 75% of doxycycline and the controlled-release portion contains 25% of doxycycline. 
     
     
         22 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 65% of doxycycline and the controlled-release portion contains 35% of doxycycline. 
     
     
         23 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 66% of doxycycline and the controlled-release portion contains 34% of doxycycline. 
     
     
         24 . The low dose once daily tablet according to  claim 13 , wherein the immediate-release portion contains 60% of doxycycline and the controlled-release portion contains 40% of doxycycline. 
     
     
         25 . A low dose once daily tablet comprising doxycycline at a sub-antibiotic dose and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect, and wherein the tablet comprises only an immediate-release portion. 
     
     
         26 . The low dose once daily tablet comprising  claim 25 , wherein the immediate-release portion comprises from 24 mg to 36 mg of doxycycline. 
     
     
         27 . A low dose once daily tablet comprising doxycycline at a sub-antibiotic dose and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect, and wherein the tablet comprises only a controlled-release portion. 
     
     
         28 . The low dose once daily tablet comprising  claim 27 , wherein the controlled-release portion may comprise from 24 mg to 36 mg of doxycycline. 
     
     
         29 . A method of treating rosacea by administering to a person in need thereof a low dose once daily tablet comprising (i) 50% to 99% of doxycycline and one or more pharmaceutically acceptable excipients as an immediate-release portion; and (ii) 1% to 50% of doxycycline, a controlled-release polymer, and one or more pharmaceutically acceptable excipients as a controlled-release portion, wherein the once daily tablet provides a total daily dosage of 24 mg to 36 mg when administered once daily. 
     
     
         30 . The method of treating rosacea according to  claim 29 , wherein the tablet exhibits a reduced food effect.