Raloxifene sprinkle composition

#The present invention relates to a capsule composition comprising plurality of particulates comprising a) a core comprising raloxifene, and b) a taste-masking coating present in an amount of from about 0.5% to about 50% w/w based on the core weight.

#Raloxifene is indicated for the treatment of osteoporosis and breast cancer in postmenopausal women. It is commercially available as immediate release tablets (Evista®) in the U.S. The development of raloxifene composition has been hindered, due to low water solubility which can adversely affect the bioavailability and manufacturing process. U.S. Pat. No. 6,458,811 discloses raloxifene having a mean particle size of less than 25 microns, which allows enhanced bioavailability and control during the manufacturing process. It further discloses granular compositions comprising raloxifene, which can be compressed into tablet dosage forms or can be filled into capsules.

#Raloxifene is known to possess a bitter taste. Raloxifene is categorized as a drug that should be “handled as hazardous” by the National Institute for Occupational Safety and Health (U.S.). Further, the summary of product characteristic by the European Medicines Agency instructs to “not break or crush” Evista® tablets, as they may taste bad. Handling of uncoated granules and crushed tablets would also be hazardous for the compounding pharmacist.

#A first aspect of the present invention relates to a capsule composition of raloxifene comprising plurality of particulates s, wherein said capsules release not more than 40% of raloxifene in 10 minutes, when measured in a United States Pharmacopeia (USP) type 2 dissolution apparatus, paddle at 50 RPM, at a temperature of 37° C.±0.5° C. in 1000 mL of pH 4.5 acetate buffer and 0.05% sodium lauryl sulfate.

#A second aspect of the present invention relates to a capsule composition of raloxifene comprising plurality of particulates, wherein said capsules release not more than 85% of raloxifene in 10 minutes, when measured in a USP type 2 dissolution apparatus, paddle at 100 RPM, at a temperature of 37° C.±0.5° C. in 1000 mL of water, 0.5% polysorbate, and an enzyme.

#According to one embodiment of this aspect, the raloxifene may be present in an amount of from about 10% to about 80% based on the total weight of composition. In particular, from about 15% to about 80% based on the total weight of composition, wherein the capsule shell weight is not included in the total weight of composition.