US 2010O278754A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0278754 A1 Stroppolo et al. (43) Pub. Date: Nov. 4, 2010 (54) ORALLY DISINTEGRATING TABLETS WITH (86). PCT No.: PCT/EP09/S1055 SPECKLED APPEARANCE S371 (c)(1), 2), (4) Date: Jul. 6, 2010 (75) Inventors: Federico Stroppolo, Mezzovico (2), (4) (CH); Shahbaz Ardalan Related U.S. Application Data Mezzovico (CH) (60) Provisional application No. 61/026,249, filed on Feb. 5, 2008. Correspondence Address: Publication Classification ROTHWELL, FIGG, ERNST & MANBECK, PC. 51) int. C 1425 KSTREET, N.W., SUITE 800 (51) Eikyu (2006.01) WASHINGTON, DC 20005 (US) A69/20 (2006.01) (52) U.S. Cl. ....................................... 424/10.2: 424/10.3 (73) Assignee: ALPEX PHARMASA, MEZZOVICO (CH) (57) ABSTRACT Orally disintegrating tablets containing colored granules of a (21) Appl. No.: 12/811,737 water-soluble Sugar which give them a speckled appearance y x- - - 9 are described. The orally disintegrating tablets with speckled appearance are readily and easy identifiable by physicians, (22) PCT Filed: Jan. 30, 2009 nurses and patients. US 2010/0278754 A1 Nov. 4, 2010 ORALLY DISINTEGRATING TABLETS WITH Surface are easily visible, making Such tablets more identifi SPECKLED APPEARANCE able than white or monocolored tablets. 0016 Solid or semisolid forms with speckled appearance are very common among cosmetic and laundry products, such 0001. The present invention generally relates to the iden as tooth pastes or soaps. tification of orally disintegrating tablets. More particularly, 0017. They are prepared by incorporating colored beads of the invention relates to orally disintegrating tablets with a different material into the composition. speckled appearance for their easy identification by physi 0018. In case of ODT, the colored beads must be soluble cians, nurses and patients. and dissolve as fast as the tablets to avoid an unpleasant 0002 Solid pharmaceutical dosage forms for oral admin grinding sensation when the tablet disintegrates in the oral istration are usually in pill, tablet or capsule form. These cavity. Moreover, the colored beads must be stable, i.e. they dosage forms are available in a limited variety of shapes, size, must not release the color during storage, and should give and colors, and many of them are very similar to each other in minimal coloration of the oral cavity after disintegration of their outward appearance. the tablet. 0003 Frequently, users confuse such dosage forms, par 0019. The present invention relates to orally disintegrating ticularly if they are elderly or have limited vision. The con tablets containing colored granules which give a speckled sequences of taking the wrong medication can be life-threat appearance to the tablets for their readily and easy identifica ening. For this reason Health Authorities require that each dosage form and strength must be clearly identified simply by tion by physicians, nurses and patients. individual visual inspection. 0020. The orally disintegrating tablets of the invention 0004 Identification of tablets is usually made by using contains colored granules of a water-soluble Sugar. different shapes, sizes, or colors, or by color coating, printing 0021. The present invention relates to orally disintegrating or embossing them. Very often a double identification is tablets (ODT) with speckled appearance which make them required such as embossing and coloring, or coating and readily identifiable by users. printing, etc. 0022. The ODT with speckled appearance are prepared by 0005 Also correct intake of drugs is important for their mixing Soluble colored granules to the pharmaceutically effectiveness. acceptable carrier. 0006 Conventional tablets are swallowed, usually with 0023 The term “colored granules” as used herein after some water or other liquids, and the absorption of the active means granules of a color different from the color of the ingredient occurs in the gastro-intestinal tract. tablet. Colored granules are, for example, blue or yellow 0007 Orally Disintegrating Tablets (ODT) dissolve in the granules in a white tablet, blue or white granules in a yellow oral cavity by contact with saliva, do not require water for tablet, yellow or white granules in a blue tablet, dark blue ingestion and could permit a buccal absorption of the active granules in a light blue tablet, blue granules and red granules ingredient. The advantageous properties of ODT over con in a white tablet, etc. ventional tablets are making them always more and more 0024. The soluble colored granules are granular particles popular for drug administrations. of a water-soluble Sugar Such as Sucrose or a polyalcohol. 0008 For their correct intake, it would be very helpful if Specific examples of polyalcohols are Sorbitol, mannitol, ODT were more easily detectable and identifiable over con Xylitol, fructose, etc. ventional tablets. 0025 Preferably, the same polyalcohol already present in 0009. In case of ODT physical identification methods are the pharmaceutically acceptable carrier of the ODT is used limited because ODT tablets are characterized by a low hard for the preparation of the colored granules of the invention. ness which allows their rapid dissolution when in contact with (0026. Preferably, the ODT of the present invention con saliva (i.e. EU pharmacopoeia requires a disintegration time tains colored granules of mannitol. of not more than 3 minutes in water). 0027 Even if water-soluble sugars are excipients usually 0010 Coating is not usually used because it could delay present in ODT, their use to prepare colored granules suitable saliva penetration in the tablets, so delaying their disintegra for the preparation of ODT with speckled appearance tion. requires a specific particle size. 0011. As a consequence, identification of ODT by printing 0028. In fact, the particle size of the colored granules is is also unusual because this technique requires a smooth and critical. Colored granules with too small particle size are not shining tablet Surface. Such as a film- or a Sugar-coated tablet. visible and the resulting tablets have no speckled appearance. 0012 Embossing is possible but the dimension of charac On the other side, the use of colored granules with too large ters is usually too small, due to the limited tablet surface, to be particle size results in a tablet which appears uniformly col easily read by elderly people or by people with a limited ored and therefore not readily identifiable over mono-colored vision. tablets. 0013 Colored ODT can be prepared but the limited num 0029. The colored granules used in the ODT of the present ber of pharmaceutically acceptable colors make difficult to invention have a particle size from about 10um to about 1200 obtain an ODT easily identifiable over conventional colored um, preferably from about 200 um to about 800 um, most tablets. preferably from about 300 um to about 500 um. 0014. One way to solve the problem would be to make 0030. The selection of the particle size of the colored ODT identifiable by using a particular colored pattern. granules of the ODT of the present invention depends on 00.15 ODT with speckled (spotted) appearance, i.e. with a several factors. Since the sucrose or polyalcohol used for the bicolored appearance characterized by the presence of spots colored granules is preferably one of the excipients already of a different color on their surface can be easily identified by present in the ODT, the particle size must be different from users. For example, blue spots on a white or yellow tablet the particle size of the already present excipient. US 2010/0278754 A1 Nov. 4, 2010 0031. The selection of the suitable particle size also fedrine, reproterol, salmeterol, soterenol, terbutaline, depends on the desired colored pattern. For example, the use tulobuterol, and Xanoterol, C-adrenergic blockers such as of a little quantity of large particles tends to produce an ODT dapiprazole, fenspiride, nicergoline, prazosin, and yohim with few large colored spots on its surface. Higher amount of bine; B-adrenergic blockers such as acebutolol, alprenolol. Smaller particles tends to produce less discrete colored spots atenolol, befnolol, betaxolol, bupranolol, carazolol, carteolol, on the surface of the tablets. celiprolol, indenolol, levobunolol, mepindolol, metipranolol. 0032. Then, the amount of colored granules suitable for moprolol, pindolol, practolol, propranolol, and timolol; each tablet, according to the present invention, can vary adrenocortical steroid; adrenocorticotropic hormones such as within a relatively large range depending on the particle size ACTH cosintropin; alcohol deterrents such as calcium ciana of the granule. Preferably, the amount of colored granules mide citrate, and disulfiram; aldose reductase inhibitors such ranges between about 0.1% w/w and about 50% w/w, still as epalrestat, tolrestat, and Zopolrestat; aldosterone antago more preferably between about 1% w/w and about 30% w/w. nists such as canrenone, and spironolattone; anabolics Such as 0033 Preferably the colored granules useful for the ODT androisoxazole, androstenediol, methandriol, methenolon, with speckled appearance of the present invention are pre methyltrienolone, and nandrolone; narcotic analgesics Such pared by granulation of the water-soluble Sugar with an aque as alfentanil, buprenorphine, codeine and its derivatives, fen ous Suspension or solution of the coloring agent in a Suitable tanil, meperidine, methadone, morphine and its derivatives, fluid