US 2005O147672A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0147672 A1 Ohmori et al. (43) Pub. Date: Jul. 7, 2005 (54) TABLETS QUICKLY DISINTEGRATING IN (30) Foreign Application Priority Data MOUTH Jun. 29, 1999 (JP)....................................... 183624/1999 (76) Inventors: Shinji Ohmori, Nishinomiya-shi (JP); Yasuo Ohno, Osaka-shi (JP); Tadashi Makino, Ibaraki-shi (JP) Publication Classification Correspondence Address: 5 1. Int.nt. Cl."Cl. ......................... A61K 31/68 5; A61K 9/20; WENDEROTH, LIND & PONACK, L.L.P. A61K 35/78 2033 K STREET N. W. SUTE 800 (52) U.S. Cl. ............................. 424/464; 424/725; 514/78 WASHINGTON, DC 20006-1021 (US) (21) Appl. No.: 11/035,956 (57) ABSTRACT (22) Filed: Jan. 18, 2005 Tablets quickly disintegrating in the mouth which comprise Related U.S. Application Data a bitter drug ingredient and a bitterneSS-reducing ingredient composed of an essential oil, a high Sweetness-Sweetener (62) Division of application No. 10/395,137, filed on Mar. and/or an acidic phospholipid or its lyso-derivative. When 25, 2003, which is a division of application No. taken even without water, these tablets exhibit little bitter 09/869,979, filed on Aug. 20, 2001, now abandoned, neSS. Thus, a bitter drug ingredient can be formulated filed as 371 of international application No. PCT/ without coating into tablets quickly disintegrating in the JP00/04081, filed on Jun. 22, 2000. mouth. US 2005/0147672 A1 Jul. 7, 2005 TABLETS QUICKLY DISINTEGRATING IN (for example, JP 10-306038A), that of using a sugar alcohol MOUTH (for example, JP 10-53538 A), that of using an essential oil or an essential oil component (for example, JP5-255126 A), FIELD OF THE INVENTION that of using an acidic phospholipid (for examples, JP 62-265234, JP8-9897 A, JP 7-67552 A, and the like), and so 0001. The present invention relates to tablets quickly O. disintegrating in the mouth, wherein the bitterneSS is reduced. More particularly, it relates to tablets quickly 0007. However, they are strictly the technologies of disintegrating in the mouth, wherein a bitter drug ingredient reducing the bitterneSS for general preparations on the can be formulated without coating by compounding a bit premise that Such a preparation is to be taken together with terneSS-reducing ingredient. water, whereby, when these technologies were applied, as they are, to tablets quickly disintegrating in the mouth, BACKGROUND ART which were intended to be taken without water, the effect of reducing the bitterneSS was not Sufficient and one had not 0002 In recent years, in order to improve QOL (quality been able to obtain practical tablets quickly disintegrating in of life) of patients, tablets quickly disintegrating in the the mouth. mouth have received attention as a dosage form that can be taken easily by Senior perSons or children having a low OBJECTS OF THE INVENTION Swallowing ability. 0008. The object of the present invention is to provide 0003) Nevertheless, in the case where a bitter drug ingre tablets quickly disintegrating in the mouth without coating a dient is formulated in tablets quickly disintegrating in the bitter drug ingredient as mentioned above, which can be mouth, the tablets are immediately disintegrated in the taken easily with the bitterneSS being hardly perceived even mouth to expose the bitter drug ingredient in the mouth. In when taken without water addition in this case, because of being taken without water, tablets quickly disintegrating in the mouth result in percep SUMMARY OF THE INVENTION tion of a strong bitterneSS for a longer time than general tablets for internal use, thereby giving a great demerit to the 0009. As a result of intensive investigations to solve the tablets quickly disintegrating in the mouth, which are char above-mentioned problems, the present inventors have acterized by easy dosing. found that a combination of an essential oil that has been heretofore known to reduce the bitterneSS, a high SweetneSS 0004. In order to solve the above-mentioned problems, Sweetener and/or an acidic phospholipid or its lySO-deriva there has been proposed a method that comprises coating a tive particularly exerts a significant effect to reduce the bitter drug ingredient, which is to be formulated in tablets bitterneSS, thereby resulting in the completion of the present quickly disintegrating in the mouth, with a high molecular invention on the basis of Such a finding. compound Such as ethyl cellulose, Eudragit, or the like to prevent a direct exposure of Said drug ingredient even if Said 0010 That is, the present invention provides: tablets are disintegrated in the mouth (JP 6-5021294 A). However, if the bitter drug ingredient is coated with an 0011 (1) A tablet quickly disintegrating in the aqueous coating agent, a Sufficient coating effect cannot be mouth which comprises a bitter drug ingredient and obtained owing to a low Strength of the resultant coat. On the a bitterneSS-reducing ingredient composed of an contrary, a Sufficient coating effect can be obtained by essential oil, a high Sweetness-Sweetener and/or an coating using an organic Solvent, but there will arise prob acidic phospholipid or its lySO-derivative; lems involving a residual Solvent in the coat, an operational 0012 (2) The tablet quickly disintegrating in the environment at the production Such as inhalation of the mouth according to the above (1), wherein the bit organic Solvent by operators, possible hazards at the opera terneSS-reducing ingredient is composed of an essen tion Such as a fire and an explosion, and So on. Also, Such tial oil and a high SweetneSS-Sweetener; a coating has a demerit of requiring an operation for a long time and a facility. 0013 (3) The tablet quickly disintegrating in the mouth according to the above (1), wherein the bit 0005 Furthermore, in the case where the coating layer is terneSS-reducing ingredient is composed of an essen thickened in order to inhibit the bitterness sufficiently and prevent breakage of the coat upon tabletting, elution of the tial oil and an acidic phospholipid or its lyso-deriva drug ingredient is delayed, resulting in a preparation from tive; which merely about 30% of the drug ingredient is eluted 0014 (4) The tablet quickly disintegrating in the even after 60 minutes, for example in the dissolution test. mouth according to the above (1), wherein the bit 0006. On the other hand, also in the field of granules, terneSS-reducing ingredient is composed of essential powders, liquids and Solutions, and the like, technologies to oil, a high Sweetness-Sweetener, and an acidic phos reduce the bitterness have been heretofore developed. There pholipid or its lySO-derivative; have been proposed a number of technologies in order to 0015 (5) The tablet quickly disintegrating in the reduce the bitterneSS, for example, a technology of com mouth according to the above (1), wherein the bitter pounding stevia (JP 10-101582 A) or aspartame (JP 2-56416 drug ingredient is not coated; A), which is classified as a so-called high Sweetness-Sweet ener, that of compounding a combination of a flavor and a 0016 (6) The tablet quickly disintegrating in the Sweetener (JP 10-273435 A), that of compounding a sugar mouth according to the above (1), wherein the bitter alcohol and Thaumatin, one of high SweetneSS-Sweeteners, drug ingredient is acetaminophen; US 2005/0147672 A1 Jul. 7, 2005 0017 (7) The tablet quickly disintegrating in the the like; a bronchodilator Such as methylephedrine hydro mouth according to the above (1), wherein the essen chloride (including the d-form and the d1 form), ephedrine tial oil is mint oil; hydrochloride, or the like; an antituSSive agent Such as codeine, codeine phosphate, dihydrocodeine phosphate, 0018 (8) The tablet quickly disintegrating in the dextromethorphan hydrobromide, noScapine, dimenorfan, mouth according to the above (1), wherein the high guaiacolsulfonic acid, guaifenesin, or the like; an expecto Sweetness-Sweetener is one or two members be rant agent Such as potassium guaiacoSulfonate, brom hexine Selected from Stevia and aspartame; and hydrochloride, or the like; a cholagogue drug Such as 0019 (9) The tablet quickly disintegrating in the urSOdeoxycholic acid, chenodeoxycholic acid, or the like; an mouth according to the above (1), wherein the acidic antidiarrheal agent Such as loperamide hydrochloride or the phospholipid or its lyso-derivative is Soybean leci like; a Sedative hipnotic drug Such as bromoValerylurea or the like, an antianxiety agent Such as diazepam or the like; thin. a prophylactic/therapeutic agent against motion Sickness such as dimenhydrinate or the like; vitamin B, family Such DETAILED DESCRIPTION OF THE as thiamine hydrochloride, thiamine mononitrate, bisthia INVENTION mine nitrate, thiamine disulfide, thiamine dicetylsulfate, 0020 Hereinafter, the present invention will be described dicethiamine hydrochloride, furSultiamine, furSultiamine in detail. In the present specification, the tablets quickly hydrochloride, octotiamine, cycotiamine, bisibuthiamine, disintegrating in the mouth refer to a Solid drug preparation bisbentiamine, proSultiamine, benfotiamine, dibenzoyl thia that disintegrates within a time shorter than about 90 sec mine, thiamine pyrophosphate, or the like, Vitamin B family onds, preferably about 60 Seconds, without mastication, in Such as riboflavin Sodium phosphate or the like; Vitamin Be the presence of Saliva in the mouth. family Such as pyridoxine hydrochloride or the like, calcium pantothenate; Vitamin