Gemcabene combinations for the treatment of cardiovascular disease

Abstract

The present invention provides pharmaceutical compositions formulated to include a statin and gemcabene, wherein the composition is useful for treating, preventing, or reducing the symptoms of cardiovascular and metabolic indications that involve elevate levels of LDL cholesterol, triglycerides, or both.

1 . 93 . (canceled) 
     
     
         94 . A tablet comprising:
 a core, the core comprising a statin or a pharmaceutically acceptable salt thereof; and   an enteric coating comprising a first copolymer or a second copolymer,
 the first copolymer is a methyl acrylate, methyl methacrylate and methacrylic acid copolymer, and 
 the second copolymer is methacrylic acid copolymer type C, 
   wherein the amount of the enteric coating ranges from about 2% w/w to about 15% w/w of the core.   
     
     
         95 . The tablet of  claim 94 , wherein the enteric coating comprises the first copolymer and the second copolymer. 
     
     
         96 . The tablet of  claim 94 , wherein the amount of the enteric coating is about 10% w/w of the core. 
     
     
         97 . The tablet of  claim 95 , wherein the ratio of the first copolymer to the second copolymer ranges from about 2:1 to about 1:2 by weight. 
     
     
         98 . The tablet of  claim 94 , wherein the amount of the first copolymer ranges from 0% w/w to about 10%) w/w of the core. 
     
     
         99 . The tablet of  claim 94 , wherein the amount of the second copolymer ranges from 0% w/w to about 10% w/w of the core. 
     
     
         100 . The tablet of  claim 94 , further comprising a subcoating between the core and the enteric coating. 
     
     
         101 . The tablet of  claim 100 , wherein the amount of the subcoating ranges from about 1% w/w to about 5% w/w of the core. 
     
     
         102 . The tablet of  100 , wherein the subcoating comprises hypromellose. 
     
     
         103 . The tablet of  claim 94 , wherein the statin is atorvastatin, simvastatin, pravastatin, mevastatin, rosuvastatin, fluvastatin, lovastatin, pitavastatin, dalvastatin, dihydrocompactin or orcerivastatin. 
     
     
         104 . The tablet of  claim 94 , wherein the statin is atorvastatin. 
     
     
         105 . The tablet of  claims 94 , wherein the pharmaceutically acceptable salt of the statin is atorvastatin calcium. 
     
     
         106 . The tablet of  claim 94 , wherein the amount of the statin or pharmaceutically acceptable salt thereof ranges from about 10% to about 80% w/w of the core. 
     
     
         107 . The tablet of  claim 94 , wherein the amount of the statin or pharmaceutically acceptable salt thereof ranges from about 1 mg to about 80 mg. 
     
     
         108 . The tablet of  claim 94 , wherein when the tablet is subjected to dissolution testing according to USP <711> Delayed Release Dosage Forms Method A using Apparatus 2 (Paddle Apparatus) at 100 RPM, no more than 5% of the statin is detected in an acidic dissolution medium 2 hours after operation of Apparatus 2, wherein the acidic dissolution medium is 0.1N HCl. 
     
     
         109 . The tablet of  claim 94 , wherein the tablet is a microtablet having a diameter ranging from about 10 μm to about 3 mm. 
     
     
         110 . The tablet of  claim 94 , further comprising another pharmaceutically active agent. 
     
     
         111 . The tablet of  claim 110 , wherein the other pharmaceutically active agent is ezetimibe, gemcabene or a pharmaceutically acceptable salt thereof. 
     
     
         112 . The tablet of  claim 110 , wherein the other pharmaceutically active agent is gemcabene calcium. 
     
     
         113 . The tablet of  claim 112 , further comprising ezetimibe. 
     
     
         114 . An oral dosage form comprising the tablet of  claim 94  and a composition comprising another pharmaceutically active agent. 
     
     
         115 . The oral dosage form of  claim 114 , wherein the other pharmaceutically active agent is ezetimibe, gemcabene or a pharmaceutically acceptable salt thereof. 
     
     
         116 . The oral dosage form of  claim 114 , wherein the other pharmaceutically active agent is gemcabene calcium. 
     
     
         117 . The oral dosage form of  claim 117 , further comprising ezetimibe. 
     
     
         118 . A capsule containing the tablet of  claim 94 . 
     
     
         119 . The capsule of  claim 118 , further containing another pharmaceutically active agent. 
     
     
         120 . The capsule of  claim 119 , wherein the other pharmaceutically active agent is ezetimibe, gemcabene, or a pharmaceutically acceptable salt thereof. 
     
     
         121 . The capsule of  claim 119 , wherein the other pharmaceutically active agent is gemcabene or a pharmaceutically acceptable salt thereof. 
     
     
         122 . The capsule of  claim 119 , wherein the other pharmaceutically active agent is gemcabene calcium. 
     
     
         123 . The capsule of  claim 121 , wherein the gemcabene or pharmaceutically acceptable salt thereof is present in an amount ranging from about 50 mg to about 900 mg per capsule. 
     
     
         124 . The capsule of  claim 121 , further containing ezetimibe or a pharmaceutically acceptable salt thereof. 
     
     
         125 . A kit comprising a tablet of  claim 94  and instructions for use of the tablet.