Liquid crystalline dosage form for administering a statin

Abstract

A composition including an amphiphilic compound capable of self-assembling into liquid crystalline particles and a statin for systemic administration via oral mucosa. A method of lowering blood cholesterol levels in a subject comprising administering the self-assembling liquid crystalline particles and statin via oral mucosa. Preferred dosage forms result in prolonged release of the statin.

1 . A method of lowering blood cholesterol levels in a subject in need thereof comprising administering a solid composition to the oral mucosa of the subject, wherein the composition comprises an amphiphilic compound capable of self-assembling into a liquid crystalline phase upon contact with a hydrophilic solvent and a statin compound, and wherein the statin compound is systemically administered via the oral mucosa. 
     
     
         2 . The method of  claim 1 , wherein the composition prolongs the release of the statin compound. 
     
     
         3 . The method of  claim 1 , wherein the administration is sublingual or buccal. 
     
     
         4 . The method of  claim 1 , wherein the method includes treating or preventing the development of dyslipidaemia, cardiovascular disease or atherosclerosis. 
     
     
         5 . The method of  claim 4 , wherein the dyslipidaemia is hyperlipidaemia. 
     
     
         6 . The method of  claim 1 , wherein the subject is identified as in need of blood cholesterol lowering. 
     
     
         7 . The method of  claim 1 , wherein the statin is administered at a dose of 0.5 to 30 mg/day. 
     
     
         8 . The method of  claim 1 , wherein the method results in a reduction in total cholesterol of about 15% to about 30%. 
     
     
         9 . The method of  claim 1 , wherein the method results in a reduction in LDL-C of about 25% to about 50%. 
     
     
         10 . The method of  claim 8 , wherein the method results in the reduction in total cholesterol within 14 days. 
     
     
         11 . The method of  claim 1 , wherein the solid composition is an oral disintegrating tablet. 
     
     
         12 . The method of  claim 11 , wherein tablet retains about 90% or more of the active ingredient following storage at 25° C./60% RH for at least 6 months. 
     
     
         13 . The method of  claim 1 , wherein the amphiphilic compound is about 1 to 20% w/w of the composition. 
     
     
         14 . The method of  claim 1 , wherein the w/w ratio of amphiphilic compound to statin is about 1:1 to 7:1. 
     
     
         15 . The method of  claim 1 , wherein the self-assembled particles are cubosomes or hexasomes. 
     
     
         16 . The method of  claim 1 , wherein the statin compound is rosuvastatin or atorvastatin. 
     
     
         17 . The method of  claim 1 , wherein the amphiphilic compound has a critical packing parameter of >1/2 and/or a hydrophilic lipophilic balance of 0 to <10. 
     
     
         18 . The method of  claim 1 , wherein the amphiphilic compound is a mono- and/or di-glyceride of a fatty acid comprising a 6 to 24 carbon chain. 
     
     
         19 . The method of  claim 1 , wherein the amphiphilic compound is a glycerol monooleate. 
     
     
         20 . The method of  claim 1 , wherein the statin is administered at a dose of 0.5 to 7 mg/day.