Claims for Patent: 9,511,031

Summary for Patent: 9,511,031

Title:	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.
Inventor(s):	Lukas; Stefan (Manningham, AU), Lepore; Angelo (Rostrevor, AU), Mudge; Stuart (Northcote, AU)
Assignee:	Mayne Pharma International Pty. Ltd. (Salisbury South, AU)
Application Number:	14/973,149
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,511,031
Patent Claims:	1. A dosage form, comprising doxycycline combined with a controlled release composition, wherein said dosage form comprises 60, 90, or 120 mg of doxycycline, and at pH 5.0 the normalized average release of doxycycline 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; wherein when the amount of doxycycline of said dosage form is 60 mg, after administration of a single dose under fasting conditions to a patient in need thereof, the average C.sub.max is about 80% to about 125% of about 625-1600 ng/ml; or wherein when the amount of doxycycline of said dosage form is 90 mg, after administration of a single dose under fasting conditions to a patient in need thereof, the average C.sub.max is about 80% to about 125% of about 1100-2400 ng/ml; or wherein when the amount of doxycycline of said dosage form is 120 mg, after administration of a single dose under fasting conditions to a patient in need thereof, the average C.sub.max is about 80% to about 125% of about 1250-3200 ng/ml. 2. A dosage form, comprising doxycycline combined with a controlled release composition, wherein said dosage form comprises 60, 90, or 120 mg of doxycycline, and at pH 5.0 the normalized average release of doxycycline 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; wherein when the amount of doxycycline of said dosage form is 60 mg, after administration of a single dose to a patient in need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 10000-24000 nghr/ml; or wherein when the amount of doxycycline of said dosage form is 90 mg, after administration of a single dose to a patient need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 15000-36500 nghr/ml; or wherein when the amount of doxycycline of said dosage form is 120 mg, after administration of a single dose to a patient need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 20000-48500 nghr/ml. 3. The dosage form of claim 1, wherein at pH 5.0 the normalized average release of doxycycline 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. 4. The dosage form of claim 2, wherein at pH 5.0 the normalized average release of doxycycline 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. 5. The dosage form of claim 1, wherein at pH 5.0 the normalized average release of doxycycline 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. 6. The dosage form of claim 2, wherein at pH 5.0 the normalized average release of doxycycline 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. 7. The dosage form of claim 1, wherein at pH 5.0 the normalized average release of doxycycline at 20 minutes ranges from about 42% to about 64%. 8. The dosage form of claim 2, wherein at pH 5.0 the normalized average release of doxycycline at 20 minutes ranges from about 42% to about 64%. 9. The dosage form of claim 1, wherein at pH 5.0 the normalized average release of doxycycline at 20 minutes ranges from about 47% to about 64%. 10. The dosage form of claim 2, wherein at pH 5.0 the normalized average release of doxycycline at 20 minutes ranges from about 47% to about 64%. 11. The dosage form of claim 1, wherein at pH 5.0 the normalized average release of doxycycline at 25 minutes ranges from about 58% to about 72%. 12. The dosage form of claim 2, wherein at pH 5.0 the normalized average release of doxycycline at 25 minutes ranges from about 58% to about 72%. 13. The dosage form of claim 1, wherein at pH 5.0 the normalized average release of doxycycline at 25 minutes ranges from about 65% to about 72%. 14. The dosage form of claim 2, wherein at pH 5.0 the normalized average release of doxycycline at 25 minutes ranges from about 65% to about 72%. 15. The dosage form of claim 1, comprising a plurality of pellets, each comprising the controlled release polymer composition disposed over the doxycycline. 16. The dosage form of claim 2, comprising a plurality of pellets, each comprising the controlled release polymer composition disposed over the doxycycline. 17. The dosage form of claim 15, wherein at pH 5.0 the normalized average release of doxycycline at 25 minutes is about 60% to about 72%; wherein when the amount of doxycycline of said dosage form is 60 mg, after administration of a single dose to a patient in need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 10000-24000 nghr/ml; or wherein when the amount of doxycycline of said dosage form is 90 mg, after administration of a single dose to a patient need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 15000-36500 nghr/ml; or wherein when the amount of doxycycline of said dosage form is 120 mg, after administration of a single dose to a patient need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 20000-48500 nghr/ml. 18. The dosage form of claim 17, wherein at pH 5.0 the normalized average release of doxycycline at 25 minutes is about 65%. 19. The dosage form of claim 1, wherein said administering is once-per-day. 20. The dosage form of claim 2, wherein said administering is once-per-day. 21. The dosage form of claim 1, wherein the release of doxycycline is measured under USP <711> conditions with stirring at 50 RPM. 22. The dosage form of claim 2, wherein the release of doxycycline is measured under USP <711> conditions with stirring at 50 RPM. 23. A dosage form, comprising doxycycline combined with a controlled release composition, wherein at pH 5.0 the normalized average release of doxycycline 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; wherein after administration of a single dose under fasting conditions to a patient in need thereof, the average C.sub.max is about 80% to about 125% of about 10-27 ng/ml per mg of doxycycline administered. 24. A dosage form, comprising doxycycline combined with a controlled release composition, wherein at pH 5.0 the normalized average release of doxycycline 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; wherein after administration of a single dose to a patient in need thereof, the average AUC.sub.0-.infin. is about 80% to about 125% of about 167-404 nghr/ml per mg of doxycycline administered. 25. The dosage form of claim 23, wherein at pH 5.0 the normalized average release of doxycycline 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. 26. The dosage form of claim 24, wherein at pH 5.0 the normalized average release of doxycycline 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. 27. The dosage form of claim 23, wherein at pH 5.0 the normalized average release of doxycycline 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. 28. The dosage form of claim 24, wherein at pH 5.0 the normalized average release of doxycycline 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. 29. The dosage form of claim 23, wherein at pH 5.0 the normalized average release of doxycycline at 20 minutes ranges from about 42% to about 64%. 30. The dosage form of claim 24, wherein at pH 5.0 the normalized average release of doxycycline at 20 minutes ranges from about 42% to about 64%.