Oral tablet formulation consisting of fixed combination of rosuvastatin and ezetimibe for treatment of hyperlipidemia and cardiovascular diseases

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.