Venlafaxine Formulations and Methods of Preparing the Same

Abstract

A method of forming a multi-particulate dosage form using rotary granulation is described in which polyethylene oxide is employed as s binder in a rotary granulation process. A multi-particulate oral dosage form comprises a plurality of pellets, the pellets comprising a core having disposed thereon a core composition layer. The core composition layer comprises venlafaxine and a binder, wherein the binder comprises a polyethylene oxide. In other embodiments, the binder comprises a 1:2:1 bis (butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate.

1 . A multi-particulate oral dosage form, comprising a plurality of pellets, the pellets comprising a core having disposed thereon a core composition layer, the core composition layer comprising an admixture of a binder and a water-soluble active agent having a water solubility of about 1 to about 10 mg/ml at 25° C., wherein the binder comprises polyethylene oxide, wherein the polyethylene oxide has an average molecular weight of about 100,000 to about 6,000,000, and wherein a ratio of polyethylene oxide to active agent is about 1:30 to about 1:5. 
   
   
       2 . The multi-particulate oral dosage form of  claim 1 , wherein the binder comprises about 0.2 wt % to about 12 wt % of the total weight of the core and the core composition layer. 
   
   
       3 . The multi-particulate oral dosage form of  claim 1 , comprising about 10 wt % to about 98 wt % of the core, about 2 wt % to about 85 wt % of the active agent, and about 0.1 wt % to about 20 wt % of the binder, all based on the total weight of the core and the core composition layer. 
   
   
       4 . The multi-particulate oral dosage form of  claim 3 , comprising about 10 wt % to about 70 wt % of the active agent, based on the total weight of the core and the core composition layer. 
   
   
       5 . The multi-particulate oral dosage form of  claim 1 , further comprising an additional coating layer, wherein the additional coating layer is a controlled-release coating, a seal coating, or a combination of one or more of the foregoing coatings. 
   
   
       6 . The multi-particulate dosage form of  claim 1 , wherein the core is an inert sphere. 
   
   
       7 . The multi-particulate dosage form of  claim 6 , wherein the inert sphere comprises nonpareils, sugar spheroids, microcrystalline cellulose spheres, spheres made of microcrystalline cellulose and one or more sugars, or a combination of one or more of the foregoing cores. 
   
   
       8 . The multi-particulate dosage form of  claim 1 , wherein the inert sphere is a sugar sphere. 
   
   
       9 . The multi-particulate dosage form of  claim 1 , wherein the core composition layer further comprises a plasticizer. 
   
   
       10 . A multi-particulate oral dosage form, comprising a plurality of pellets, the pellets comprising an inert sphere core having disposed thereon a core composition layer, the core composition layer comprising an admixture of a binder and a water-soluble active agent having a water solubility of about 1 to about 10 mg/ml at 25° C., wherein the binder comprises a 1:2:1 (butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate). 
   
   
       11 . The multi-particulate oral dosage form of  claim 10 , wherein the ratio of binder to active agent in the core composition layer is about 1:30 to about 1:5. 
   
   
       12 . The multi-particulate oral dosage form of  claim 10 , wherein the binder comprises about 0.2 wt % to about 12 wt % of the total weight of the core and the core composition layer. 
   
   
       13 . The multi-particulate oral dosage form of  claim 10 , comprising about 10 wt % to about 98 wt % of the core, about 2 wt % to about 85 wt % of the active agent, and about 0.1 wt % to about 20 wt % of the binder, all based on the total weight of the core and the core composition layer. 
   
   
       14 . The multi-particulate oral dosage form of  claim 13 , comprising about 10 wt % to about 70 wt % of the active agent, based on the total weight of the core and the core composition layer. 
   
   
       15 . The multi-particulate oral dosage form of  claim 1 , further comprising an additional coating layer, wherein the additional coating layer is a controlled-release coating, a seal coating, or a combination of one or more of the foregoing coatings. 
   
   
       16 . The multi-particulate dosage form of  claim 10 , wherein the inert sphere is a sugar sphere. 
   
   
       17 . A method of making a multi-particulate oral dosage form of  claim 1 , comprising
 mixing the active agent, the binder comprising polyethylene oxide, and a dispersing agent to form a coating mixture, and   atomizing the coating mixture in the presence of a plurality of cores in a fluidized bed with a rotor-disk granulator to produce a plurality of pellets, the pellets comprising the core having disposed thereon a core composition layer comprising the active agent and the binder.