Pharmaceutical composition of doxycycline with reduced food effect

Patent metadata

Field	Value
Publication number	US-9463196-B2
Application number	US-201514821263-A
Country	US
Kind code	B2
Filing date	Aug 7, 2015
Priority date	Jul 9, 2014
Publication date	Oct 11, 2016
Grant date	Oct 11, 2016

Abstract

The present invention relates to a once daily tablet comprising doxycycline at sub-antibiotic dose and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect. The invention further provides a method of treatment of rosacea by administering to a person in need thereof the doxycycline tablet with or without food. A process of preparing the tablet is also provided.

First claim

We claim:

1. A once daily tablet comprising doxycycline and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect such that the food effect on C max is less than 40% compared to when the tablet is administered in a fasted state, and the food effect on AUC 0-t is less than 20% compared to when the tablet is administered in a fasted state.

2. The once daily tablet according to claim 1 , wherein the once daily tablet comprises (i) 50% to 99% of doxycycline and one or more pharmaceutically acceptable excipients as an immediate-release portion; and (ii) 1% to 50% of doxycycline, a controlled-release polymer, and one or more pharmaceutically acceptable excipients as a controlled-release portion.

3. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 85% of doxycycline and the controlled-release portion contains 15% of doxycycline.

4. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 34 mg of doxycycline and the controlled-release portion contains 6 mg of doxycycline.

5. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 75% of doxycycline and the controlled-release portion contains 25% of doxycycline.

6. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 30 mg of doxycycline and the controlled-release portion contains 10 mg of doxycycline.

7. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 66% of doxycycline and the controlled-release portion contains 34% of doxycycline.

8. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 26.4 mg of doxycycline and the controlled-release portion contains 13.6 mg of doxycycline.

9. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 65% of doxycycline and the controlled-release portion contains 35% of doxycycline.

10. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 26 mg of doxycycline and the controlled-release portion contains 14 mg of doxycycline.

11. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 60% of doxycycline and the controlled-release portion contains 40% of doxycycline.

12. The once daily tablet according to claim 2 , wherein the immediate-release portion contains 24 mg of doxycycline and the controlled-release portion contains 16 mg of doxycycline.

13. A process for the preparation of a once daily tablet comprising doxycycline and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect, wherein the process comprises:
a) preparing an immediate release portion comprising doxycycline and one or more pharmaceutically acceptable excipients;
b) preparing a controlled release portion comprising doxycycline, a controlled-release polymer, and one or more pharmaceutically acceptable excipients; and
c) formulating the immediate-release portion and the controlled-release portion into a tablet.

14. The process according to claim 13 , wherein the tablet is a bilayered tablet.

15. The process according to claim 13 , wherein the tablet comprises only an immediate-release portion.

16. The process according to claim 13 , wherein the tablet comprises only a controlled-release portion.

17. A method of treating rosacea by administering to a person in need thereof a once daily tablet comprising doxycycline and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect such that the food effect on C max is less than 40% compared to when the tablet is administered in a fasted state, and the food effect on AUC 0-t is less than 20% compared to when the tablet is administered in a fasted state.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Sharma Ravish Kumar
• Metia Pulak Kumar
• Singh Ravinder
• Shear Rajesh Srikrishan
• Fanda Anuj Kumar
• Jain Satish Kumar
• Singh Romi Barat
• Pappu Swarna
• Konatham Prabhakar
• Katikaneni Pruthvipathy
• Jami Dileep

Classifications

• A61K31/65 Primary

  Tetracyclines · CPC title

• A61K9/2081

  with microcapsules or coated microparticles according to A61K9/50 · CPC title

• A61K9/2027

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/1676

  having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921) · CPC title

• A61K9/209

  containing drug in at least two layers or in the core and in at least one outer layer · CPC title