method for manufacturing a pharmaceutical composition for controlled release of an active substance

Abstract

The present invention pertains to a sized product, which contains a drug, polyethylene oxide with a molecular weight of 2,000,000 or higher, and a specific size controlling agent for polyethylene oxide (substance with the appropriate plasticity and binding force) and wherein at least the above-mentioned specific size controlling agent is uniformly dispersed in the above-mentioned polyethylene oxide, a controlled-release pharmaceutical composition containing this sized product, and a method of manufacturing a controlled-release pharmaceutical composition containing this sized product. A controlled-release pharmaceutical composition with good uniformity of content can be presented by using powder particles of polyethylene oxide with powder properties suitable for tableting, which is obtained by uniform dispersion of the specific size controlling agent for polyethylene oxide of the present invention.

1 . A process for making a pharmaceutical preparation for controlled release comprising a sized product, said process comprising:
 admixing a drug and a size controlling agent to form a suspension or aqueous solution; and   spraying said suspension or aqueous solution onto a polyethylene oxide having a viscosity-average molecular weight of 2,000,000 or more to form a sized product, wherein said sized product is a collection of particles, each particle having an average diameter of approximately 60 μm to 300 μm.   
   
   
       2 . The process according to  claim 1 , wherein the size controlling agent is one or two or more selected from the group consisting of polyethylene glycol, hydroxypropylmethyl cellulose of 2 to 15 mPa·s (2% w/v), hydroxypropylmethyl cellulose of 2 to 10 mPa·s (2% w/v), and methyl cellulose of 2 to 15 mPa·s (2% w/v). 
   
   
       3 . The process according to  claim 1 , wherein the amount of size controlling agent is 0.5 to 60 wt % per polyethylene oxide. 
   
   
       4 . The process according to  claim 1 , wherein when polyethylene glycol is selected as a size controlling agent, the amount is 0.5 to 60 wt % per unit of the pharmaceutical preparation. 
   
   
       5 . The process according to  claim 1 , wherein the amount of polyethylene oxide is 10 to 95 wt % per unit of the pharmaceutical preparation. 
   
   
       6 . The process according to  claim 1 , wherein the amount of polyethylene oxide added is at least 70 mg per unit of the pharmaceutical preparation. 
   
   
       7 . The process according to  claim 1 , wherein the viscosity-average molecular weight of polyethylene oxide is 5,000,000 or higher. 
   
   
       8 . The process according to  claim 1 , wherein said process further comprises admixing a hydrophilic base with said drug. 
   
   
       9 . The process according to  claim 8 , wherein the amount of water required to dissolve 1 g of said hydrophilic base is 5 ml or less (20±5° C.). 
   
   
       10 . The process according to  claim 9 , wherein the hydrophilic base is a member selected from the group consisting of polyethylene glycol, sucrose, and polyvinyl pyrrolidone. 
   
   
       11 . The process according to  claim 8 , wherein the amount of hydrophilic base is 5 to 80 wt % per unit of the pharmaceutical preparation. 
   
   
       12 . The process according to  claim 1 , which further comprises yellow ferric oxide and/or red ferric oxide. 
   
   
       13 . The process according to  claim 12 , wherein the amount of yellow ferric oxide and/or ferric oxide is 0.3 to 20 wt % per polyethylene oxide. 
   
   
       14 . The process according to  claim 1 , wherein the amount of drug is 85 wt % or less per unit of the pharmaceutical preparation. 
   
   
       15 . The process according to  claim 14 , wherein the amount of drug is 10 wt % or less per unit of the pharmaceutical preparation. 
   
   
       16 . The process according to  claim 1 , wherein the drug is tamsulosin hydrochloride. 
   
   
       17 . The process according to  claim 1 , which comprises essentially no organic solvent. 
   
   
       18 . The process according to  claim 1 , wherein the spraying is a member selected from the group consisting of a high-shear agitation granulation method, a crushing (pulverization) granulation method, a fluidized bed granulation method or device, an extrusion granulation method, a tumbling granulation method or device, and a spray granulation method or device. 
   
   
       19 . The process according to  claim 18 , wherein the spraying is a member selected from the group consisting of a fluidized bed granulation method or device and a tumbling fluidized bed granulation or device. 
   
   
       20 . The process according to  claim 2 , wherein polyethylene glycol is used in liquid form at 10 wt % or less, per PEO. 
   
   
       21 . The process according to  claim 1 , wherein water is added during spraying by a process selected from the group consisting of a continuous spraying method whereby water is continuously added and an intermittent spraying method whereby a drying process and further, a shaking process are included in the granulation process.