Modified release doxycycline composition

Abstract

Doxycycline formulations with a reduced food effect are disclosed. Particularly disclosed are modified release formulations which can be administered once a day and exhibit a reduced food effect. Methods of treating inflammatory conductions such as rosacea or inflammatory symptoms such as the papules and pustules of rosacea or acne vulgaris are also disclosed.

1 - 11 . (canceled) 
     
     
         12 . A method of treating inflammatory rosacea or an inflammatory symptom of either rosacea or acne vulgaris comprising administering to a human patient in need thereof a modified release oral composition comprising:
 (i) about 30 to less than about 50 mg of doxycycline, based on the equivalent weight of doxycycline base, wherein the doxycycline is in an amount of about 15-20% w/w;   (ii) about 10-18% w/w of one or more water soluble and insoluble polymers; and   (iii) about 1-20% w/w of one or more pharmaceutically acceptable excipients;   wherein the composition is free of any immediate release component; and wherein the composition provides at least one of the following pharmacokinetic parameters:
 (a) average input rate of about 4 ng/hr/mL to about 15 ng/hr/mL during a time period of T 0  min to T 30  min, and 
 (b) average input rate of about 15 ng/hr/mL to about 40 ng/hr/mL during a time period of T 0  min to T 60  min. 
   
     
     
         13 . The method according to  claim 12 , wherein the doxycycline is an acid addition salt of doxycycline. 
     
     
         14 . The method according to  claim 13 , wherein the acid addition salt of doxycycline is doxycycline hyclate. 
     
     
         15 . The method according to  claim 14 , wherein the doxycycline hyclate is present in an amount of about 46 mg. 
     
     
         16 . The method according to  claim 12 , wherein the composition exhibits a reduced food effect selected from the group consisting of an AUC of less than about 15% and a C max  of less than about 40% upon oral administration to a human. 
     
     
         17 . The method according to  claim 16 , wherein the composition exhibits a reduced food effect as a C max  of less than about 35% upon oral administration to a human. 
     
     
         18 . The method according to  claim 12 , wherein the composition provides a reduced food effect whereby both AUC and a C max  are lower than the food effect of commercially available 40 mg doxycycline compositions by at least about 15%. 
     
     
         19 . The method according to  claim 12 , where the composition upon oral administration in a fasting state exhibits bioequivalence to a commercially available 40 mg doxycycline composition and wherein the bioequivalence is established by:
 (a) a 90% Confidence Interval for mean AUC (0-t) , which is between 80% and 125%,   (b) a 90% Confidence Interval for mean AUC (0-∞) , which is between 80% and 125%, and   (c) a 90% Confidence Interval for mean C max , which is between 80% and 125%.   
     
     
         20 . The method according to  claim 12 , wherein the doxycycline is present in an amount of about 30 to about 45 mg, based on the equivalent weight of doxycycline base. 
     
     
         21 . The method according to  claim 12 , wherein the doxycycline is present in an amount of about 35 to about 45 mg, based on the equivalent weight of doxycycline base. 
     
     
         22 . The method according to  claim 12 , wherein the inflammatory symptom of either rosacea or acne vulgaris is papules and pustules of either rosacea or acne vulgaris. 
     
     
         23 . The method according to  claim 12 , for the treatment of inflammatory rosacea or an inflammatory symptom of rosacea. 
     
     
         24 . The method according to  claim 12 , wherein the composition provides a pharmacokinetic parameter of an average input rate of about 5 ng/hr/mL to about 8 ng/hr/mL during a time period of T 0  min to T 30  min. 
     
     
         25 . The method according to  claim 12 , wherein the composition provides a pharmacokinetic parameter of an average input rate of about 15 ng/hr/mL to about 20 ng/hr/mL during a time period of T 0  min to T 60  min. 
     
     
         26 . The method according to  claim 12 , wherein wherein the composition has a dC/dT value of less than about 80% of the dC/dT value provided by the commercially available 40 mg doxycycline composition, measured in a single dose human pharmacokinetic study in a fasting state and in a time period of T 0  min to T 60  mins. 
     
     
         27 . The method according to  claim 26 , wherein the composition has a dC/dT value of less than about 40% of the dC/dT value provided by the commercially available 40 mg doxycycline composition.