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. 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 one or more water soluble and insoluble polymers; and
(iii) about 1-20% w/w one or more pharmaceutically acceptable excipients;
wherein the composition is free of any immediate release component; and
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.
2. The method of claim 1 , wherein the doxycycline is an acid addition salt of doxycycline.
3. The method of claim 2 , wherein the acid addition salt of doxycycline is doxycycline hyclate.
4. The method of claim 3 , wherein the doxycycline hyclate is present in an amount of about 46 mg.
5. The method of claim 1 , 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.
6. The method of claim 1 , 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%.
7. The method of claim 1 , 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%.
8. The method of claim 1 , wherein the doxycycline is present in an amount of about 30 to about 45 mg, based on the equivalent weight of doxycycline base.
9. The method of claim 1 , wherein the doxycycline is present in an amount of about 35 to about 45 mg, based on the equivalent weight of doxycycline base.
10. The method of claim 1 , wherein the inflammatory symptom of either rosacea or acne vulgaris is papules and pustules of either rosacea or acne vulgaris.
11. The method of claim 1 , for the treatment of inflammatory rosacea or an inflammatory symptom of rosacea.