WO1999055311A1 - Comprimes se desagregeant rapidement dans la cavite buccale et procede de production desdits comprimes - Google Patents

Comprimes se desagregeant rapidement dans la cavite buccale et procede de production desdits comprimes Download PDF

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Publication number
WO1999055311A1
WO1999055311A1 PCT/JP1999/002188 JP9902188W WO9955311A1 WO 1999055311 A1 WO1999055311 A1 WO 1999055311A1 JP 9902188 W JP9902188 W JP 9902188W WO 9955311 A1 WO9955311 A1 WO 9955311A1
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WO
WIPO (PCT)
Prior art keywords
tablet
oral cavity
hardness
tableting
tablets
Prior art date
Application number
PCT/JP1999/002188
Other languages
English (en)
Japanese (ja)
Inventor
Akio Miwa
Nobuko Maeta
Original Assignee
Taisho Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co., Ltd. filed Critical Taisho Pharmaceutical Co., Ltd.
Priority to AU35360/99A priority Critical patent/AU3536099A/en
Publication of WO1999055311A1 publication Critical patent/WO1999055311A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Definitions

  • the present invention relates to a tablet that rapidly disintegrates or dissolves in the oral cavity, and a method for producing the tablet.
  • quick-disintegrating tablets manufactured by the freeze-drying method have such a hardness that the tablets cannot be extruded when removed from PTP packaging. Since it is low, it is necessary to use a packaging material with a structure that removes the seal on the back of the container and removes the quick-disintegrating tablet. In addition, tablets are easily broken and cracked during the formulation process, while carrying and taking the tablet, and there is a problem in handling.
  • a rotary tableting machine is generally used for tableting, but in order to obtain a sufficient tablet hardness to maintain the shape of the tablet in the manufacturing process and the distribution process, a large tableting machine is required. Tablet pressure is required, and as a result, it is difficult to maintain the tablet's rapid disintegration at the same time.
  • an oral rapid disintegrating tablet is manufactured without using a rotary tablet press, capital investment and special technical development will be required.
  • the present invention provides a rapidly disintegrating tablet which is excellent in disintegration and handling properties in the oral cavity while using a rotary breaker, and a method for producing the same. Disclosure of the invention
  • a desired orally disintegrating tablet can be produced by preparing granules obtained by wet granulation of an excipient and adding granules of crystalline cellulose to the granules and tableting. That is, the present invention provides a granule prepared by wet granulation of a saccharide having high solubility in water and a swellable excipient, an orally rapidly disintegrating tablet obtained by tableting crystalline cellulose, and its production. Is the way.
  • the quick disintegrating tablet of the present invention can be prepared by the following steps.
  • a sugar and a swelling excipient are mixed, and a binder is added to the mixture, if necessary, to produce granules having high compressibility and high solubility using a wet granulation method.
  • the granules are further compressed with microcrystalline cellulose and compressed at a low compression pressure.
  • a rapidly disintegrating buccal tablet having excellent ingestibility and rapidly disintegrating in the oral cavity in about 5 seconds to several tens of seconds can be prepared.
  • the quick-disintegrating tablet of the present invention obtained as described above has a hardness that can be extruded from the PTP package.
  • the quick-disintegrating tablet of the present invention has a hardness such that it can be extruded from a PTP package frequently used for tablet packaging without breaking or breaking when pushed out with a finger before taking the tablet.
  • saccharide used in the present invention a saccharide excellent in solubility in water is used.
  • sucrose, sorbitol, erythritol, and xylitol can be used.
  • erythritol and xylitol are particularly preferable in that they have a refreshing feeling and high solubility, and are particularly preferable.
  • These saccharides may be used alone or in combination of two or more.
  • the amount of the saccharide in the granule is preferably large in consideration of solubility in the oral cavity, and is 40% by weight or more, preferably 60 to 95% by weight, based on the whole granule.
  • the swellable excipient contained in the granules of the present invention is not particularly limited as long as it is an excipient having a property of swelling in the presence of water.
  • crystalline cellulose, calcium propyloxymethylcellulose (CMC-Ca), low-substituted hydroxypropyl cellulose (L-HPC), crospovidone, croscarmellose sodium and the like can be exemplified.
  • These swellable excipients may be used alone or in combination of two or more, and the combination of microcrystalline cellulose and crospovidone is most preferred, particularly in view of the hardness and disintegration of the quick disintegrating tablet.
  • the incorporation of swellable excipients into the granules not only improves the tablet's compression Important in avoiding obstacles.
  • the amount of the swellable excipient in the granule varies depending on the type of the swellable excipient. The amount is 40% or less, preferably 5 to 20% by weight, more preferably 10 to 15% based on the whole granule. is there.
  • Examples of the wet granulation method that can be performed in the present invention include high-speed stirring granulation, kneading granulation, fluidized bed granulation, and tumbling fluidized bed granulation, and the like.
  • a fluidized granulator is preferred.
  • a granulator such as a spray dryer can also be used.
  • various granulators commercially available according to each method may be used in accordance with the operation method of the equipment.
  • the method of adding the binder includes adding the binder as a powder before granulation, dissolving the binder in a granulation solvent, or adding both to the powder before granulation and the granulation solvent. Either method can be used.
  • the weight of the binder derived from the granulation solvent be 4% by weight or less, particularly 2% by weight or less of the whole granules.
  • Microcrystalline cellulose which is tableted together with the granules thus obtained, is extremely important in relation to the disintegration and strength of the tablet and the tableting trouble at the time of preparation.
  • the amount of the tablet it is necessary to keep the amount of the tablet to a level that does not increase the roughness in the oral cavity, but it is preferably 30% by weight or less, more preferably 15% by weight or less based on the weight of the tablet. And it is sufficient.
  • lubrication may be added when tableting a mixture of the above granules and crystalline cellulose.
  • examples of the lubricant that can be used in the present invention include magnesium stearate and calcium stearate.
  • a method of using a lubricant either a method of adding the lubricant to a mixed powder to be compressed or a method of directly attaching a lubricant to a punch or a die at the time of compression may be used.
  • the amount of the lubricant is preferably 0.5% by weight or less based on the whole tablet.
  • the hardness (required hardness) required for the rapidly disintegrating buccal tablet that can be extruded from the PTP package of the present invention depends on the diameter of the tablet to be prepared. For example, when the tablet diameter is 6 mm or 8 mm, The required hardness is 1 kg, the required hardness is 2 kg when the tablet diameter is 10 mm, and the required hardness is 3 kg when the tablet diameter is 15 mm or 20 mm. In addition, the tableting pressure for obtaining the above required hardness needs to be appropriately adjusted depending on the weight and shape of the tablet.
  • Tablet weight and the use of a rotary type tableting machine which is a common tableting machine, when preparing an intraoral quick disintegrating tablet having a tablet diameter of 8 mm and a corner plane shown in Examples 1 to 3
  • Table 1 shows the relationship with the tableting pressure. The hardness was measured 10 times using a Schleunigel hardness tester, and the results were shown as an average.
  • the tableting pressure may be adjusted according to the change in the diameter, weight, and shape of the tablet based on the above example.
  • the rapidly disintegrating buccal tablet of the present invention can be produced in the above-described manner at the time of tableting by using an excipient as a bulking agent (including an excipient for direct compression), a flavoring agent, and a disintegration aid.
  • an excipient as a bulking agent (including an excipient for direct compression), a flavoring agent, and a disintegration aid.
  • a light gay acid anhydride or the like known as an agent or the like can be used as appropriate.
  • the drug can be arbitrarily compounded in or outside the granules.
  • drugs that have unpleasant tastes masked by an appropriate method drugs that have been pre-granulated to avoid incompatibilities, hydrophobic coatings, gastric coatings, or enteric coatings to control the release rate of the drugs
  • Microcapsules or the like provided with a coating or the like can also be used in the present invention.
  • the drugs that can be used in the present invention are not limited by their physical properties, and include anti-inflammatory drugs, vasodilators, central nervous drugs, psychotropic drugs, antimanic drugs, antihistamines, laxatives, vitamins, intestinal drugs, gastrointestinal drugs. , Antihypertensive, antihypertensive, antiplatelet aggregating agent, antipyretic, antitussive, antiasthmatic, antispasmodic, antispasmodic, diuretic, anticancer, peptide drug, anthelmintic, antibiotic, nutrient tonic Any drug that can be administered orally can be used.
  • Industrial applicability any drug that can be administered orally can be used.
  • the orally rapidly disintegrating tablet of the present invention can be easily produced by using general tablet production equipment as it is, is excellent in disintegration and feeling of taking, and can be extruded from a PTP packaging material and taken out. It is also excellent in operability such as being possible.
  • Erythritol fine powder 5 43.6 g, 72 g of crystalline cellulose, 36 g of crospovidone, 36 g of HPC, 7.2 g of light caffeic anhydride were mixed, and the mixture was mixed with 36 mesh (M). It was sieved (mixed powder of Example 1 in Table 2). This mixed powder is converted to a fluidized bed granulator (FL The mixture was granulated using an aqueous suspension containing 1% of HPC and 2.5% of light caffeic anhydride (the binding solution of Example 1 in Table 2).
  • Example 2 The same operation as in Example 1 was performed except that the raw material components shown in Example 2 in Table 2 were used and a tumbling fluidized-granulator (Nummarmerizer I NQ-160, manufactured by Fuji Padal) was used. A square flat tablet was obtained.
  • a tumbling fluidized-granulator Namarmerizer I NQ-160, manufactured by Fuji Padal
  • Example 3 Using the raw material components shown in Example 3 in Table 2, except for the light gay anhydride in the binder solution, the same operation as in Example 1 was carried out except that a tumbling fluidized bed granulator was further used. A tablet having a 0-angle flat surface was obtained.
  • Example 4 Using the raw material components shown in Example 4 in Table 2, a fluidized bed granulator (FLO1, manufactured by Freund) was used as the granulator, and the same operation as in Example 1 was performed (tabletting machine: Collect G12, manufactured by Kikusui Seisakusho) to obtain a tablet having an 8 mm 0-corner plane.
  • FLO1 fluidized bed granulator
  • Example 4 The same operation as in Example 4 was performed, except that erythritol of the raw material component shown in Example 4 in Table 2 was changed to xylitol, to obtain a tablet having an 8 mm 0-corner plane.
  • Example 4 The same operation as in Example 4 was performed, except that erythritol as a raw material component shown in Example 4 in Table 2 was changed to sorbitol, to obtain a tablet having an 8 mm 0-corner plane.
  • Example 7 Using the raw material components shown in Example 7 in Table 2, a fluidized bed granulator (FL-1; manufactured by Freund) was used as the granulator, and the same operation as in Example 4 was performed (tabletting machine: Collect). 12, Kikusui Seisakusho) to obtain a tablet having an 8 mm 0-corner flat surface. Table 2 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7
  • Example 4 The same operation as in Example 4 was performed except that the extracellular crystalline cellulose shown in Example 4 in Table 2 was extracted and the equivalent amount was increased as erythritol in the granule, to obtain a tablet having a flat surface of 8 mm0 corner. (Comparative Example 4 in Table 3).
  • Example 4 The same operation as in Example 4 was carried out except that the extracellular crystalline cellulose shown in Example 4 in Table 2 was changed to crospovidone, to obtain a tablet having an 8 mm 0-corner plane (Comparative Example 5 in Table 3). o
  • Example 4 The same operation as in Example 4 was performed except that the extracellular crystalline cellulose shown in Example 4 in Table 2 was changed to crospovidone, and the weight was further reduced, to obtain a tablet having an 8 mm 0-corner plane (see Table 3). Comparative Example 6).
  • Example 7 The same operation as in Example 4 was carried out except that the extragranular crystalline cellulose shown in Example 4 in Table 2 was changed to L-HPC to obtain a tablet having an 8 mm 0-corner plane (comparison with Table 3). Example 7). Table 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7
  • the hardness and disintegration time in the oral cavity of the tablets obtained in Examples 1 to 3 and Comparative Examples 1 to 3 were measured.
  • the hardness was measured 10 times using a Schleunigel hardness meter, and the results were shown as the average.
  • the disintegration time in the oral cavity was measured by measuring the time required for a healthy adult male to disintegrate in the oral cavity and completely disintegrate. Table 4 shows the results.
  • Comparative Example 1 was obtained by replacing erythritol, a sugar with high solubility in water, with lactose with low solubility in water. The tablet disintegrates in about 30 seconds. However, no tablet which collapsed in about 10 seconds was obtained even if the tablet was compressed at a low compression pressure. Comparative Example 2 was prepared by a direct compression method without performing wet granulation. However, the tablet hardness was low. Conversely, when the tablet was strongly compressed to increase the hardness, rapid disintegration was lost. In Comparative Example 3, although a large amount of swellable fiber was blended, a rough feeling in the oral cavity was observed. A decrease in sex was observed.
  • Table 5 shows the oral disintegration time of the tablets obtained in Example 4 and Comparative Examples 4 to 7 in terms of hardness of 4 kg.
  • FIG. 1 shows the measured values of the push-up rail values of the present invention described in Example 4 and the tablet described in Comparative Example 47.
  • FIG. 2 shows the measured values of the tablet hardness of the present invention described in Example 4 and the tablet described in Comparative Example 47.

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  • Pharmacology & Pharmacy (AREA)
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Abstract

On décrit des comprimés qui se désagrègent ou se dissolvent rapidement dans la cavité buccale sans nécessité de recourir à un quelconque dispositif particulier, et peuvent être extrudés à partir d'emballages PTP. Ces comprimés qui se désagrègent rapidement dans la cavité buccale sont produits par conditionnement de granules en comprimés réalisé par granulation au mouillé de sucres très solubles dans l'eau et gonflement d'agents de remplissage additionnés de cellulose cristalline.
PCT/JP1999/002188 1998-04-27 1999-04-23 Comprimes se desagregeant rapidement dans la cavite buccale et procede de production desdits comprimes WO1999055311A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU35360/99A AU3536099A (en) 1998-04-27 1999-04-23 Tablets quickly disintegrated in oral cavity and process for producing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10/117179 1998-04-27
JP11717998 1998-04-27

Publications (1)

Publication Number Publication Date
WO1999055311A1 true WO1999055311A1 (fr) 1999-11-04

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PCT/JP1999/002188 WO1999055311A1 (fr) 1998-04-27 1999-04-23 Comprimes se desagregeant rapidement dans la cavite buccale et procede de production desdits comprimes

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2302650A1 (es) * 2007-01-11 2008-07-16 Tedec-Meiji Farma, S.A. Composicion de rapida desintegracion en la cavidad bucal.
JP2014218447A (ja) * 2013-05-02 2014-11-20 旭化成ケミカルズ株式会社 結晶セルロースの複合組成物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH048288A (ja) * 1990-04-26 1992-01-13 Amano Pharmaceut Co Ltd 酵素含有易崩性錠剤の製造法
JPH09309822A (ja) * 1992-02-18 1997-12-02 Nippon Shinyaku Co Ltd 口腔内溶解型速溶錠
JPH10182436A (ja) * 1996-10-31 1998-07-07 Takeda Chem Ind Ltd 固形医薬製剤
JPH10298062A (ja) * 1997-04-24 1998-11-10 Pfizer Pharmaceut Co Ltd 口腔内速溶型錠剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH048288A (ja) * 1990-04-26 1992-01-13 Amano Pharmaceut Co Ltd 酵素含有易崩性錠剤の製造法
JPH09309822A (ja) * 1992-02-18 1997-12-02 Nippon Shinyaku Co Ltd 口腔内溶解型速溶錠
JPH10182436A (ja) * 1996-10-31 1998-07-07 Takeda Chem Ind Ltd 固形医薬製剤
JPH10298062A (ja) * 1997-04-24 1998-11-10 Pfizer Pharmaceut Co Ltd 口腔内速溶型錠剤

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2302650A1 (es) * 2007-01-11 2008-07-16 Tedec-Meiji Farma, S.A. Composicion de rapida desintegracion en la cavidad bucal.
JP2014218447A (ja) * 2013-05-02 2014-11-20 旭化成ケミカルズ株式会社 結晶セルロースの複合組成物

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AU3536099A (en) 1999-11-16

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