Coated tablet

#This is a U.S. national phase application under 35 U.S.C. §371 of International Patent Application No. PCT/JP2007/061777, filed Jun. 12, 2007, and claims the benefit of Japanese Patent Application No. 2006-162972, filed Jun. 13, 2006. The International Application was published in Japanese on Dec. 21, 2007 as WO 2007/145191. The disclosures of all the prior applications are hereby incorporated by reference in their entireties.

#The present invention relates to a coated tablet which is coated with a polyvinyl alcohol copolymer for film coating.

#For example, it is reported that, when a commercial metformin hydrochloride-containing tablet and a commercial olmesartan medoxomil-containing tablet are packed together in a one-dose pack, then the metformin hydrochloride-containing tablet turns reddish. This phenomenon is assumed to be caused by the event that the (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (hereinafter referred to as “DOMDO”) group released from olmesartan medoxomil in the olmesartan medoxomil-containing tablet is hydrolyzed and converted into diacetyl and acetoin, and then these react with the guanidino group of metformin hydrochloride in the metformin hydrochloride-containing tablet. This reaction is known as Voges-Proskauel (VP) reaction. As a matter of course, however, the discoloration of drugs is unfavorable and it is considered necessary to prevent the discoloration by means of some devices in drug preparation methods.

#FIG. 1 Color change profile of tablets is shown. The vertical axis indicates color difference (ΔE), and the horizontal axis indicates time (week). In the drawing, -□- indicates the result of coated tablets of the present invention of Example 1; -Δ- indicates the result of hydroxypropylmethyl cellulose 2910-coated tablets of Comparative Example 1; and -●- indicates the result of Glycoran tablets (uncoated tablets).

#FIG. 2 Color change profile of tablets is shown. The vertical axis indicates color difference (ΔE), and the horizontal axis indicates time (week). In the drawing, -□- indicates the result of coated tablets of the invention of Example 1; -⋄- indicates the result of PULLULAN (★)-coated tablets of Comparative Example 2; and -●- indicates the result of Glycoran tablets (uncoated tablets).

#The “PVA copolymer” used in the present invention is composed of PVA, acrylic acid and methyl methacrylic acid. The polymerization ratio of each constituent of the PVA copolymer is not particularly limited insofar as it can form a film as the PVA copolymer, and, for example, PVA is preferably within a range of from 70 to 85% by weight, acrylic acid is preferably within a range of from 2.0 to 8.0% by weight; and methyl methacrylate is preferably within a range of from 17 to 21% by weight. More preferably, PVA is within a range of from 75 to 80% by weight; acrylic acid is within a range of from 2.5 to 7.5% by weight; and methyl methacrylate is within a range of from 17.5 to 20% by weight.

#The suitable “PVA” as one of the constituents of the PVA copolymer is such that the polymerization ratio is, for example, within the range of from 400 to 600, preferably within the range of from 450 to 550, and the degree of saponification is, for example, within the range of from 85 to 90 mol %, preferably within the range of from 86 to 89 mol %.

#The PVA copolymer may be a commercial POVACOAT (registered mark, Nisshin-Kasei) in which PVA, acrylic acid and methyl methacrylate are copolymerised at a ratio of 80.0% by weight, 2.5% by weight and 17.5% by weight, respectively, and polymerization degree of the said PVA is 500 and saponification degree of the said PVA is within a range of from 86.5 to 89.0 mol % by weight.