process for granulating polyethylene oxide

Polyethylene oxides are known to form a dissolution rate-controlling matrix for therapeutically active dosage forms. In order to prepare solid dosage forms from polyethylene oxide powder, a drug and optionally auxiliary ingredients, it is necessary to process the mixture by wet granulation in a manner to improve their uniformity, flowability and cohesiveness which will enable the material to be fabricated by conventional processes, such as tableting, encapsulation or molding into a satisfactory unit form which can suitably deliver an agent into the environment of use.

Various processes have been developed for modifying starting powders or other particulate material into larger permanent free-flowing agglomerates or granules referred to collectively as “granulation”. One process makes use of an organic solvent such as an alcohol. When water is used as a granulation medium, sometimes polyethylene oxide forms wet agglomerates when it comes into contact with droplets of water. Depending on the process used for granulation, some formation of lumps may be observed.

         It has been found that lump formation of polyethylene oxide upon contact with water can be reduced or eliminated when the granulation is carried out in the presence of a salt comprising a polyvalent anion at a concentration of from 0.1M to 10M in a liquid diluent which comprises (i) from 10 to 100 weight percent of water and (ii) from 90 to 0 weight percent of a protic organic solvent. Generally from 100 g to 50 kg, typically from 500 g to 2000 g of solid material can be granulated without a significant formation of lumps.

Polyethylene oxide is a nonionic homopolymer of the formula –(O - CH₂ - CH₂ -)–_n, wherein n represents the average number of oxyethylene groups. Generally n is from 1,000 to 250,000, preferably from 2,000 to 200,000. Preferred molecular weights range from 50,000 to 10,000,000, more preferably from 100,000 to 8,000,000, most preferably from 200,000 to 8,000,000. Polyethylene oxide resins are commercially available as a white powder in several grades, which differ in molecular weight, under the trademark Polyox^TM water soluble resins from Union Carbide Corporation, a subsidiary of The Dow Chemical Company. Preferred Polyox water soluble resins are designated as POLYOX WSR N-10, N-80, N-750, N-300, 205, 1105, N-12K, N-60K, 301, Coagulant, 303 or 308.

Polyethylene oxide can be granulated alone or in combination with one or more other components. The solid composition preferably comprises from 10 to 99 weight percent, more preferably from 15 to 90 weight percent, most preferably from 25 to 70 weight percent of polyethylene oxide, based on the total weight of the solid composition. Preferably, polyethylene oxide forms the matrix of a solid composition to be granulated.

Typically the solid composition to be granulated also comprises one or more active ingredients, such as a drug which can be in powder, crystalline, amorphous...