MODIFIED RELEASE DOXYCYCLINE COMPOSITION
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.