Sustained release compositions and a method of preparing pharmaceutical compositions

Abstract

A process for the manufacture of particles comprises mechanically working a mixture of a drug and a hydrophobic and/or hydrophilic fusible carrier in a high speed mixture so as to form agglomerates, breaking the agglomerates to give controlled release particles and optionally continuing the mechanical working with the optional addition of a low percentage of the carrier or diluent.

What is claimed is:  
     
         1 . A process for the manufacture of controlled release particles, which comprises: 
 (a) mechanically working in a high-speed mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150° C. and optionally a release control component comprising a water-soluble fusible material or a particulate, soluble or insoluble organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften whereby it forms agglomerates;    (b) breaking down the agglomerates to give controlled release particles; and optionally    (c) continuing mechanically working optionally with the addition of a low percentage of the carrier or diluent; and optionally    (d) repeating steps (c) and possibly (b) one or more times.    
     
     
         2 . A process according to    claim 1   , wherein during the mechanical working, step (c), heat is supplied thereto by microwave radiation.  
     
     
         3 . A process according to    claim 2   , wherein only part of the heating is supplied by microwave radiation.  
     
     
         4 . A process according to    claim 1   , wherein said drug is morphine, tramadol, hydromorphone, oxycodone, diamorphine or a pharmaceutically acceptable salt of any one of these.  
     
     
         5 . A process according to    claim 1   , wherein said hydrophobic fusible carrier or diluent is a wax selected from the group consisting of hydrogenated vegetable oil, hydrogenated castor oil, Beeswax, Carnauba wax, microcrystalline wax and glycerol monostearate.  
     
     
         6 . A process according to    claim 1   , wherein said water-soluble fusible material optionally included in the mixture in step (a) is PEG having a molecular weight of from about 1,000 to about 20,000.  
     
     
         7 . A process according to    claim 6   , wherein said PEG has a molecular weight of from about 1,000 to about 6,000.  
     
     
         8 . A process according to    claim 6   , wherein said water-soluble fusible material is a poloxamer.  
     
     
         9 . A process according to    claim 1   , wherein the fusible carrier or diluent is added stepwise during mechanical working.  
     
     
         10 . A solid dosage form obtained by compressing particles comprising a pharmaceutically active substance in a matrix of a hydrophobic and/or hydrophilic fusible diluent or carrier having a melting point of from 35 to 150° C., the solid dosage form optionally containing conventional tabletting excipients.  
     
     
         11 . A capsule for oral dosing containing particles comprising a pharmaceutically active substance in a matrix of a hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point of from 35 to 150° C. and optionally containing conventional capsuling excipients.  
     
     
         12 . A solid dosage form according to    claim 11    wherein said particles are obtained by a process comprising the steps of mechanically working a mixture containing a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150° C. at a speed and energy input which allows the carrier or diluent to melt or soften and form particles of a desired size.  
     
     
         13 . A capsule according to    claim 11    wherein said particles are obtained by a process comprising the steps of mechanically working a mixture containing a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150° C. at a speed and energy input which allows the carrier or diluent to melt or soften and form particles of a desired size.  
     
     
         14 . A solid dosage form according to    claim 10   , wherein said particles are obtained by mechanically working a mixture comprising the active ingredient, a hydrophobic and/or hydrophilic fusible carrier or diluent and optionally a release modifier in a high speed mixer at a rate and energy input sufficient to cause the fusible material to melt or soften whereby it forms particles with the active ingredient and thereafter separating particles having a desired size range.  
     
     
         15 . A capsule according to    claim 10   , wherein said particles are obtained by mechanically working a mixture comprising the active ingredient, a hydrophobic and/or hydrophilic fusible carrier or diluent and optionally a release modifier in a high speed mixer at a rate and energy input sufficient to cause the fusible material to melt or soften whereby it forms particles with the active ingredient and thereafter separating particles having a desired size range.  
     
     
         16 . A solid dosage form according to    claim 10   , wherein said particles contain a release modifier which is a hydrophilic release modifier, or a water soluble or insoluble particulate organic or inorganic material.  
     
     
         17 . A capsule according to    claim 11   , wherein said particles contain a release modifier which is a hydrophilic release modifier, or a water soluble or insoluble particulate organic or inorganic material.  
     
     
         18 . A solid dosage form according to    claim 11   , wherein the active ingredient is unstable in water.  
     
     
         19 . A capsule according to    claim 11   , wherein the active ingredient is unstable in water.  
     
     
         20 . A solid dosage form according to    claim 10   , wherein said particles are obtained by the steps comprising: 
 (a) mechanically working in a high-speed mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150° C. and optionally a release control component comprising a water-soluble fusible material or a particulate, soluble or insoluble organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften whereby it forms agglomerates;    (b) breaking down the agglomerates to give controlled release particles; and optionally    (c) continuing mechanically working optionally with the addition of a low percentage of the carrier or diluent; and optionally    (d) repeating steps (c) and possibly (b) one or more times.    
     
     
         21 . A capsule according to    claim 11   , wherein said particles are obtained by the steps comprising: 
 (a) mechanically working in a high-speed mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150° C. and optionally a release control component comprising a water-soluble fusible material or a particulate, soluble or insoluble organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften whereby it forms agglomerates;    (b) breaking down the agglomerates to give controlled release particles; and optionally    (c) continuing mechanically working optionally with the addition of a low percentage of the carrier or diluent; and optionally    (d) repeating steps (c) and possibly (b) one or more times.    
     
     
         22 . Pharmaceutical particles produced by a process comprising the steps of: 
 (a) mechanically working in a high-speed mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150° C. and optionally a release control component comprising a water-soluble fusible material or a particulate, soluble or insoluble organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften whereby it forms agglomerates;    (b) breaking down the agglomerates to give controlled release particles; and optionally    (c) continuing mechanically working optionally with the addition of a low percentage of the carrier or diluent; and optionally    (d) repeating steps (c) and possibly (b) one or more times.