Reduction of opioid blood fluctuations

Abstract

The present invention relates to the use of a sustained release matrix containing at least one opioid for producing a solid oral formulation in table form suitable for reducing blood concentration fluctuations of said opioid.

1 . Sustained-release matrix-type tablet releasing at least one opioid or one of its pharmaceutically acceptable salts, the compression matrix of said matrix-type tablet consisting of at least one excipient selected from the group comprising sustained-release pH-independent water-soluble polymers, mineral excipients and their mixtures, for its use as medicinal product administered in repeat twice-a-day form via oral route spaced apart by 8 to 14 hours and preferably 10 to 13 hours. 
     
     
         2 . Matrix-type tablet according to  claim 1 , the sustained-release, pH-independent and water-insoluble polymers being chosen from the group comprising cellulose polymers, polymers from the class of methacrylic acids, polyvinylalcohol derivatives, polymers of lactic and glycolic acids (PLGA), starches, waxes, polyvinyl acetate derivatives, polyvinyl pyrrolidone derivatives and mixtures thereof. 
     
     
         3 . Matrix-type tablet according to  claim 1  or  2 , the mineral excipients being chosen from the group comprising calcium phosphates, aluminum and silicon silicates and magnesium carbonates. 
     
     
         4 . Matrix-type tablet according to  claim 1 , coated with a sustained-release polymer, preferably ethylcellulose. 
     
     
         5 . Matrix-type tablet according to  claim 1 , maintaining the steady-state opioid plasma concentration obtained in vivo is with a reduced fluctuation at above 60% of the Css max  value, preferably above 75% of the Css max  value for at least 10 hours and preferably at least 12 hours. 
     
     
         6 . Matrix-type tablet according to  claim 1 , characterized by a  swing  parameter of less than 50%, preferably less than 25%. 
     
     
         7 . Matrix-type tablets according to  claim 1 , characterized by a  fluctuation  parameter of less than 50%, preferably less than 25%. 
     
     
         8 . Matrix-type tablet according to  claim 1 , characterized by a reduction in plasma fluctuations and in peaks and troughs, by limitation of resurgent pain due to lowered concentrations, and by limitation of episodes of acute pain. 
     
     
         9 . Matrix-type tablet according to  claim 1 , characterized by a reduction in some side effects such as nausea, drowsiness or other cognitive side effects. 
     
     
         10 . Matrix-type tablets according to  claim 1 , characterized in that the opioid is chosen from the group comprising codeine, narceine, noscapine, morphine, pholcodine, nalorphine, dihydrocodeine, hydromorphone, buprenorphine, butorphanol, dextromethorphane, nalbufine, naltrexone, naloxone, nalmefene, hydrocodone, oxymorphone and oxycodone, fentanyl, tramadol, apomorphine and etorphine, or a pharmaceutically acceptable salt thereof. 
     
     
         11 . Matrix-type tablet according to  claim 10 , characterized in that the opioid is oxycodone hydrochloride. 
     
     
         12 . Matrix-type tablet according to  claim 1 , characterized in that the compression matrix consists of a mixture of microcrystalline cellulose and polyvinyl acetate/polyvinyl pyrrolidone (80:20). 
     
     
         13 . Matrix-type tablet according to  claim 1 , characterized in that the matrix-type tablet consists of a mixture of microcrystalline cellulose and poly(ethyl acrylate/methyl methacrylate/trimethylamonioethyl methacrylate chloride) (1:2:0.2).