Controlled Release Doxycycline

Abstract

The disclosure provides controlled release compositions comprising tetracyclines and in some embodiments, doxycycline. The controlled release doxycycline compositions of the invention exhibit a superior dissolution profile and provide reduced side effects such as nausea and irritation.

What is claimed is: 
     
         1 . A dosage form, comprising: doxycycline salt and a controlled release polymer composition,
 wherein said dosage form comprising doxycycline salt maintains doxycycline base release levels measured under USP <711> conditions at pH 5 that provide a clinically effective plasma level of doxycycline base;   wherein after administration of a single dose under fasting conditions to a patient in need thereof, the average AUC 0-∞  is about 80% to about 125% of about 200-300 ng·hr/ml per mg of doxycycline base administered.   
     
     
         2 . The dosage form of  claim 1 , wherein the average AUC 0-∞  is about 80% to about 125% of about 220-225 ng·hr/ml per mg of doxycycline base administered. 
     
     
         3 . The dosage form of  claim 1 , wherein said dosage form comprises doxycycline salt in an amount equivalent to 60 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average AUC 0-∞  is about 13345±1000 ng·hr/ml. 
     
     
         4 . The dosage form of  claim 1 , wherein said dosage form comprises doxycycline salt in an amount equivalent to 120 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average AUC 0-∞  is about 26690±1000 ng·hr/ml. 
     
     
         5 . The dosage form of  claim 1 , wherein after administration of a single dose under fasting conditions to a patient in need thereof, the average C max  is about 80% to about 125% of about 10-20 ng/ml per mg of doxycycline base administered. 
     
     
         6 . The dosage form of  claim 5 , wherein the average C max  is about 80% to about 125% of about 10-15 ng/ml per mg of doxycycline base administered. 
     
     
         7 . The dosage form of  claim 1 , wherein said dosage form comprises doxycycline salt in an amount equivalent to 60 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average C max  is about 809±100 ng/ml. 
     
     
         8 . The dosage form of  claim 1 , wherein said dosage form comprises doxycycline salt in an amount equivalent to 120 mg of doxycycline base and after administration of a single dose under fasting conditions to a patient in need thereof, the average C max  is about 1619±100 ng/ml. 
     
     
         9 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions is at least one of:
 less than about 48% at 15 minutes; 
 less than about 64% at 20 minutes; and 
 less than about 72% at 25 minutes. 
 
     
     
         10 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions is at least one of:
 about 30% to about 48% at 15 minutes; 
 about 30% to about 64% at 20 minutes; and 
 about 45% to about 72% at 25 minutes. 
 
     
     
         11 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions is at least one of:
 about 35% to about 48% at 15 minutes; 
 about 40% to about 64% at 20 minutes; and 
 about 50% to about 72% at 25 minutes. 
 
     
     
         12 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 20 minutes ranges from about 42% to about 64%. 
     
     
         13 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 20 minutes ranges from about 47% to about 64%. 
     
     
         14 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 25 minutes ranges from about 58% to about 72%. 
     
     
         15 . The dosage form of  claim 1 , wherein at pH 5 the normalized average release of doxycycline base measured under USP <711> conditions at 25 minutes ranges from about 65% to about 72%. 
     
     
         16 . The dosage form of  claim 1 , wherein said dosage form comprises a doxycycline salt pellet with the controlled release polymer composition disposed thereon. 
     
     
         17 . The dosage form of  claim 1 , wherein said dosage form comprises a plurality of doxycycline salt pellets with the controlled release polymer composition disposed thereon, and contained in a capsule or tablet. 
     
     
         18 . The dosage form of  claim 1 , wherein said dosage form is a matrix composition. 
     
     
         19 . The dosage form of  claim 1 , wherein the amount of doxycycline salt of said dosage form is equivalent to 60 mg, 90 mg, or 120 mg of doxycycline base. 
     
     
         20 . The dosage form of  claim 1 , wherein the doxycycline salt is doxycycline hyclate. 
     
     
         21 . The dosage form of  claim 1 , wherein the release of doxycycline base is measured under USP <711> conditions comprising: rotating the dosage form in a USP Apparatus 1 basket at about 100 RPM, within 900 mL of a dissolution media comprising acid or buffer, which is held at a temperature of about 37° C. 
     
     
         22 . The dosage form of  claim 21 , wherein said dosage form is a tablet. 
     
     
         23 . The dosage form of  claim 1 , wherein the release of doxycycline base is measured under USP <711> conditions comprising: rotating the dosage form in a USP Apparatus 1 basket at about 50 RPM, within 900 mL of a dissolution media comprising acid or buffer, which is held at a temperature of about 37° C. 
     
     
         24 . The dosage form of  claim 23 , wherein said dosage form is a pellet.