Pharmaceutical formulation

Abstract

The instant invention provides a pharmaceutical composition comprised of a cholesterol absorption inhibitor and an HMG-CoA reductase inhibitor, one or more anti-oxidants, microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate and lactose. The composition need not contain ascorbic acid in order to obtain desirable stability.

1 - 40 . (canceled) 
     
     
         41 . A pharmaceutical composition comprised of from 1% to 20% by weight of a cholesterol absorption inhibitor; from 1% to 80% by weight of simvastatin; from 0.01% to 2% by weight of at least one antioxidant agent; and citric acid up to a maximum of 10% by weight, provided that the composition is not comprised of ascorbic acid. 
     
     
         42 . The pharmaceutical composition of  claim 41  wherein the antioxidant agent is selected from the group consisting of butylated hydroxyanisole (BHA), 2,6-di-tert-butyl-4-methylphenol (BHT), propyl gallate, edetate disodium, calcium metabisulphite and combinations thereof. 
     
     
         43 . The pharmaceutical composition of  claim 41  wherein the weight % of citric acid is from 0.1% to 1.25%. 
     
     
         44 . The pharmaceutical composition of  claim 43  wherein the weight % of citric acid is about 0.25%. 
     
     
         45 . The pharmaceutical composition of  claim 41  wherein the antioxidant agent is selected from BHA, propyl gallate and a combination thereof. 
     
     
         46 . The pharmaceutical composition of  claim 45  wherein the antioxidant agent is a combination of BHA and propyl gallate. 
     
     
         47 . The pharmaceutical composition of  claim 46  wherein the weight % of BHA is from 0.01% to 0.05%. 
     
     
         48 . The pharmaceutical composition of  claim 47  comprised of about 0.02% of BHA. 
     
     
         49 . The pharmaceutical composition of  claim 47  comprised of from 0.001% to 0.05% by weight of propyl gallate. 
     
     
         50 . The pharmaceutical composition of  claim 49  comprised of about 0.005% by weight of propyl gallate. 
     
     
         51 . The pharmaceutical composition of  claim 49  further comprised of from 5% to 20% by weight of microcrystalline cellulose; from 1% to 4% by weight of hydroxypropyl methylcellulose; and from 0.5% to 2% by weight of magnesium stearate. 
     
     
         52 . The pharmaceutical composition of  claim 49  comprised of 10% or less of croscarmellose sodium. 
     
     
         53 . The pharmaceutical composition of  claim 52  comprised of from 2% to 4% by weight of croscarmellose sodium. 
     
     
         54 . The pharmaceutical composition of  claim 41  in the form of a tablet which does not have a film coating. 
     
     
         55 . The pharmaceutical composition of  claim 54  that is not comprised of pregelatinized starch. 
     
     
         56 . The pharmaceutical composition of  claim 41 , comprised of from 1% to 80% by weight of simvastatin; from 0.01% to 2% by weight of BHA; and from 0.1% to 1.25% by weight of citric acid. 
     
     
         57 . The pharmaceutical composition of  claim 56  comprised of from 1% to 20% of simvastatin. 
     
     
         58 . The pharmaceutical composition of  claim 57  comprised of from 5% to 10% of simvastatin. 
     
     
         59 . The pharmaceutical composition of  claim 56  comprised of 0.01% to 0.05% of BHA. 
     
     
         60 . The pharmaceutical composition of  claim 59  comprised of about 0.02% of BHA. 
     
     
         61 . The pharmaceutical composition of  claim 56  further comprised of 0.2% or less by weight of propyl gallate. 
     
     
         62 . The pharmaceutical composition of  claim 61  comprised of from 0.001% to 0.05% by weight of propyl gallate. 
     
     
         63 . The pharmaceutical composition of  claim 62  comprised of about 0.005% by weight of propyl gallate. 
     
     
         64 . The pharmaceutical composition of  claim 56  further comprised of from 5% to 20% by weight of microcrystalline cellulose; from 1% to 4% by weight of hydroxypropyl methylcellulose; and from 0.5% to 2% by weight of magnesium stearate. 
     
     
         65 . The pharmaceutical composition of  claim 56  further comprised of 10% or less by weight of croscarmellose sodium. 
     
     
         66 . The pharmaceutical composition of  claim 65  comprised of from 2% to 4% by weight of croscarmellose sodium. 
     
     
         67 . The pharmaceutical composition of  claim 56  wherein the composition is a tablet and provided that the tablet does not have a film coating. 
     
     
         68 . The pharmaceutical composition of  claim 67  provided that it is not comprised of pregelatinized starch. 
     
     
         69 . A composition according to  claim 41  for use in treating a condition selected from hyperlipidemia, hypercholesterolemia and atherosclerotic disease. 
     
     
         70 . A composition according to  claim 41  for use in preventing atherosclerotic disease or myocardial infarction. 
     
     
         71 . A pharmaceutical composition comprising:
 (a) from 1% to 20% by weight of a cholesterol absorption inhibitor;   (b) from 1% to 80% by weight of at least one HMG-CoA reductase inhibitor;   (c) from 0.005% to 10% by weight of ascorbic acid;   (d) croscarmellose sodium; and   (e) povidone.   
     
     
         72 . The pharmaceutical composition according to  claim 71 , wherein the cholesterol absorption inhibitor is ezetimibe. 
     
     
         73 . The pharmaceutical composition according to  claim 71 , wherein the HMG-Co-A reductase inhibitor is simvastatin or atorvastatin.