US 10,376,470 B2
Oral tablet formulation consisting of fixed combination of rosuvastatin and ezetimibe for treatment of hyperlipidemia and cardiovascular diseases
Marie Charmaine Dias, Morristown, NJ (US); and Chandir Ramani, Brapton (CA)
Assigned to Althera Life Sciences, LLC, Morristown, NJ (US)
Filed by Althera Life Sciences, LLC, Morristown, NJ (US)
Filed on Aug. 27, 2017, as Appl. No. 15/687,492.
Application 15/687,492 is a continuation in part of application No. 14/350,905, granted, now 9,763,885, previously published as PCT/US2013/039018, filed on May 1, 2013.
Claims priority of provisional application 61/641,013, filed on May 1, 2012.
Prior Publication US 2017/0354604 A1, Dec. 14, 2017
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/00 (2006.01); A61K 31/00 (2006.01); A61K 9/24 (2006.01); A61K 31/505 (2006.01); A61K 31/397 (2006.01); A61K 9/20 (2006.01); A61K 9/28 (2006.01)
CPC A61K 9/209 (2013.01) [A61K 9/0053 (2013.01); A61K 9/2009 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2027 (2013.01); A61K 9/2054 (2013.01); A61K 9/2059 (2013.01); A61K 9/2095 (2013.01); A61K 9/2893 (2013.01); A61K 31/397 (2013.01); A61K 31/505 (2013.01)] 7 Claims
 
1. A solid dosage form of rosuvastatin and ezetimibe combined in one bilayer tablet comprising rosuvastatin in a first layer and ezetimibe in a second layer in a weight ratio of 0.5:1, 1:1 or 2:1, and wherein:
(i) rosuvastatin is formulated with microcrystalline cellulose in the first layer and ezetimibe is formulated without microcrystalline cellulose in the second layer;
(ii) the first layer comprises rosuvastatin and 1-15 wt % of pharmaceutically acceptable excipients; 0.5-10 wt % of dicalcium phosphate; 20-90 wt % of microcrystalline cellulose; 2-30 wt % of crospovidone; and 0.1-2 wt % of pharmaceutically acceptable lubricants; wherein all weight percents are based on the total weight of the first layer;
(iii) the second layer comprises ezetimibe and 2-20 wt % of pharmaceutically acceptable excipients; 20-90 wt % of mannitol; 0.5-10 wt % of binders; and 0.2-5 wt % of magnesium stearate; wherein all weight percents are based on the total weight of the second layer;
(iv) said solid dosage releases 98% of rosuvastatin and 95% of ezetimibe within 45 minutes as measured by a standard in vitro dissolution test; and wherein about 50% of the maximum concentration of rosuvastatin and about 100% of the maximum concentration of ezetimibe are absorbed in vivo into the circulation of healthy humans within 1 hour after administering; and
(v) said solid dosage form is a stable composition of rosuvastatin and ezetimibe comprising less than 0.5% of ezetimibe related impurities after 6 weeks of storage at 40° C. and 75% relative humidity, less than 0.5% of rosuvastatin related lactone impurities and less than 0.5% of rosuvastatin related keto impurities after 6 weeks of storage at 40° C. and 75% relative humidity.