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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/282—Organic compounds, e.g. fats
  • A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating

Definitions

• the present invention relates to a method for producing a stable enteric-coated sugar-coated tablet, and more particularly to a method for producing an enteric-coated sugar-coated tablet which prevents discoloration and puncture of the sugar-coated tablet with time.
• composition and formulation of the sugar-coating layer in sugar-coated tablets are diverse, and are often unknown and not yet clarified.
• a film layer, a sub-coating layer, and a smoothing layer are generally formed sequentially on a central tablet to further prevent moisture penetration. It is manufactured by forming a layer of sucrose and finally glazing it with wax.
• Sugar-coating operations are generally sub-coated to give the core tablets roundness (usually gelatin, gum arabic powder, aqueous solution of sucrose as sugar-coating solution, precipitated calcium carbonate as a spraying agent, a mixture of talc, sucrose and gum arabic powder).
• enteric-coated sugar-coated tablets are coated with an enteric polymer that dissolves in the central tablet with an alcohol and then formed into a sugar-coated layer consisting of a sub-coating layer, a smoothing layer, a coloring layer, and a fixing layer.
• enteric-coated products should be inactivated by gastric juice, such as enzymes, or stimulate the stomach, such as aspirin, or drugs that cause impaired digestion of the stomach. It is used for the preparation of drugs with certain properties.
• an acidic and substantially insoluble but alkaline and soluble polymer material such as a cellulosic, biel or acrylic resin is used.
• enteric coatings can be coated by dissolving in an organic solvent, or by using cellulosic polymers such as hydroxypropylmethylcellulose acetate succinate (HPMC AS) and propyloxymethylethylcellulose (CMEC). Is dispersed and coated in water. Latex-type water-based coating agents such as Eudragit L30D55 are often used. Recently, a method of dry-coating hydroxypropylmethylcellulose acetate succinate (HPMCAS) while spraying a liquid plasticizer has been developed.
• HPMCAS hydroxypropylmethylcellulose acetate succinate
• Japanese Patent Application Laid-Open No. 11-43430 discloses a method of adding a pigment binder to a coloring layer or a finishing layer to prevent peeling or cracking of a sugar coating layer;
• Japanese Patent Application Laid-Open No. 7-55898 describes a method for enhancing the strength of a sugar-coated tablet by applying a film made of a high molecule soluble in both water and a lower alcohol to the sugar-coated tablet.
• a method is described in which high-purity maltitol and pullulan are used in place of sucrose as sugar coating materials to increase the impact resistance and prevent cracking, breakage, and changes over time.
• none of these methods is perfect.
• Enteric polymer coating agents include cellulosic polymers such as cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), or carboxymethyl ester. Butyl cellulose (CMEC), etc .; vinyl polymers, for example, polyvinyl alcohol acetate phthalate (PV AP); acrylic polymers, for example, copolymers of methacrylic acid and ethyl acrylate (methacrylic acid copolymers L, S), etc. An acidic, substantially insoluble, but alkaline, soluble polymer material can be used.
• a preferred enteric coating is HPMCAS.
• Enteric coating can be performed by dry-coating a fine powdered enteric polymer material while spraying a liquid plasticizer onto uncoated tablets. Further, the enteric coating agent may be coated by dissolving it in an organic solvent, may be dispersed in water and coated, or may be a latex-type liquid.
• the water-soluble polymer formed on the enteric polymer coating and the water-soluble polymer of the layer of Z or water-soluble saccharide include hydroxypropylcellulose (HPC), hydroxyfilm methylcellulose (HPMC), methylcell mouth, and force.
• Water-soluble cellulosic polymers such as sodium ropoxymethylcellulose, hydroxyethylcellulose, and methylhydroxyethylcellulose; and pullulan and polyvinyl alcohol can be used. Of these, water-soluble cellulosic polymers, particularly hydroxypropylmethylcellulose (HPMC), are preferred.
• sucrose mannitol
• glucose mannitol
• lactose etc.
• water-soluble sugars be able to.
• sucrose is preferred.
• the above-mentioned water-soluble polymer and water-soluble saccharide may be used alone or in a mixture thereof, or a water-soluble saccharide may be used on a water-soluble polymer or a water-soluble saccharide may be used on a raw saccharide.
• the hydrophilic polymer may be coated.
• the layer thickness of the water-soluble polymer and / or water-soluble saccharide is 20 ⁇ m to 300 m, usually 22 to 300 wm, preferably 40 to 200 m, and particularly preferably. 4 8 to 15 ⁇ ⁇ .
• the thickness of the layer is usually 40 to 300 m, preferably 48 to 200 m, and particularly preferably 60 to 150 m.
• the thickness of the layer is usually 20 to 300 m, preferably 22 to 200 m, and particularly preferably 50 to 100 m. 1150 m. If it is less than 20 Am, sufficient puncture prevention and discoloration prevention effects cannot be obtained.
• the total thickness of both layers may be in the above range.
• the above-mentioned water-soluble polymer and water-soluble saccharide are each applied to an enteric-coated tablet in the form of an aqueous solution.
• a saccharide such as sucrose
• it is in the form of an aqueous solution of 10 to 80% (by weight)
• a water-soluble polymer such as HPMC
• an aqueous solution of 1 to 30% (by weight) is used.
• the formation of the sugar coating layer after the formation of the water-soluble polymer and / or water-soluble saccharide layer is usually performed by a sugar coating operation including at least one of sub-coating, smoothing, coloring, and finishing, and then necessary. Polishing is performed accordingly. Particularly, when the diameter of the uncoated tablet is less than 7 bands, an enteric coating layer is formed, a water-soluble saccharide layer is formed, and a water-soluble polymer (especially, HPMC) layer is formed thereon.
• a sugar-coated tablet can also be formed by forming a coloring layer using sucrose syrup. Example Next, the present invention will be described specifically with reference to examples, but the present invention is not limited thereto.
• a central tablet (uncoated tablet) having the composition shown in Table 1 below was prepared using a 5.5R, 4.5R punch with a size of 55 nig per tablet.
• the disintegrant hardness was 2.8 kg and the disintegration time (test solution: water) was 6 to 8 minutes.
• the enteric-coated film tablets prepared in Reference Example 1 were coated with a 65% sucrose syrup at 5 mg / tablet using a ventilated pan-coating device (manufactured by Heiko Ichiyuichi 48 Freund Corporation). A m layer of sucrose was formed. Further, a smoothing layer of 35 mg per tablet was formed with an aqueous suspension composed of 10% of kaolin, 10% of calcium carbonate, 5% of talc, 5% of titanium oxide, 4% of arabic gum powder and 40% of sucrose. Finally, a coloring layer of 5 mg per tablet was formed using 65% sucrose syrup to which an evening dye was added, and the mixture was glossed with wax to obtain enteric-coated sugar-coated tablets.
• the enteric-coated film tablets prepared in Reference Example 1 were sucrose 9 mg, film thickness 86 with 65% sucrose syrup using a ventilated pan-coating machine (Hikako Ichiyo 48, manufactured by Freund Corporation). Was formed. Further, a smoothing layer and a coloring layer were formed and glazed in the same manner as in Example 1 to obtain enteric-coated sugar-coated tablets.
• Example 3
• the enteric-coated film tablet produced in Reference Example 1 was Using Coater 48, Freund Sangyo Co., Ltd.), a film having a thickness of 124 mg was formed with sucrose 13 mg with syrup of 65% sucrose. Further, an enteric-coated sugar-coated tablet was obtained by forming and smoothing a smoothing layer and a coloring layer in the same manner as in Example 1.
• Example 4
• 6% hydroxypropyl methylcellulose (HPMC) (TC-5R Shin-Etsu Chemical Co., Ltd.) was applied to the enteric-coated film tablet prepared in Reference Example 1 using a ventilated pan coating machine (Hi-Ko Yuichi 48 type, Freund Sangyo Co., Ltd.).
• a smoothing layer and a coloring layer were formed and glazed in the same manner as in Example 1 to obtain enteric-coated sugar-coated tablets.
• 6% hydroxypropyl methylcellulose (TC-5R Shin-Etsu Chemical Co., Ltd.) was applied to the enteric-coated film tablet manufactured in Reference Example 1 using a ventilated pan-coating device (Hikko Itsuya- 48, manufactured by Freund Corporation).
• a water-soluble film having a thickness of 52 im and a thickness of 52 mg was prepared from an aqueous solution of hydroxypropyl propylmethylcellulose (7 mg). Further, a smoothing layer and a coloring layer were formed and glazed in the same manner as in Example 1 to obtain enteric-coated sugar-coated tablets.
• the enteric-coated film tablet prepared in Reference Example 1 was applied to a sucrose syrup of 65% with a sucrose of 6% and a film thickness of 57 m using a ventilated pan-coating device (Hachiko Co., Ltd., type 48 Freund Corporation). Then, a 10% aqueous solution of hydroxypropylmethylcellulose (75 mg in thickness) was formed with a 6% aqueous solution of hydroxypropylmethylcellulose (TC-15R manufactured by Shin-Etsu Chemical Co., Ltd.). Lastly, a 5% per-pill coating layer was formed with 65% sucrose syrup to which an evening dye had been added, and the tablets were glossed to give enteric-coated sugar-coated tablets.
• the enteric-coated film tablets prepared in Reference Example 1 were applied to a 10% calcium carbonate, 5% talc, 5% titanium oxide, and 5% titanium oxide by using a ventilated pan coating machine (manufactured by Hikko Yuichi 48 Freund Corporation).
• An aqueous suspension composed of 4% of rubber powder and 40% of sucrose formed a smoothing layer of 35 mg per tablet.
• a coloring layer of 5 mg per tablet was formed with 65% sucrose syrup to which a tar dye had been added, and the tablets were glossed to give enteric-coated sugar-coated tablets.
• the enteric film tablets prepared in Reference Example 1 were applied to a 65% sucrose syrup using a ventilated pan-coating machine (Hicoater 48, Freund Corporation) to produce 2 mg of sucrose and a film thickness of 19 m. Was formed. Further, a smoothing layer and a coloring layer were formed and glazed in the same manner as in Example 1 to obtain enteric-coated sugar-coated tablets. Comparative Example 3
• 6% hydroxypropyl methylcellulose (TC-15R Shin-Etsu Chemical Co., Ltd.) was applied to the enteric-coated film tablets prepared in Reference Example 1 using a ventilated pan coating machine (Hachikoa 48 type, Freund Sangyo Co., Ltd.). 2) Hydroxypropyl methylcellulose 2 mg, 15 m thick water-soluble film layer was formed with the aqueous solution. Further, a smoothing layer and a coloring layer were formed and glazed in the same manner as in Example 1 to obtain an enteric sugar-coated tablet.
• the enteric-coated sugar tablets obtained in Examples 1 to 8 and Comparative Examples 1 to 3 were stored at 50 ° C, and punctures and appearance changes of the dragees after one month were observed. The results are shown in Table 2.
• ⁇ indicates a value obtained by measuring a sample at 50 ° C for one month using a color difference meter SQ2000 (manufactured by Nippon Denshoku Industries Co., Ltd.) at the time of manufacture of each sample.
• the present invention by coating a water-soluble polymer and / or a water-soluble saccharide on an enteric film, it becomes possible to produce a stable enteric-coated sugar-coated tablet without discoloration and puncture of the sugar-coated tablet.

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Citations (5)

• 2001
  • 2001-06-15 JP JP2001181989A patent/JP4856323B2/ja not_active Expired - Fee Related
• 2002
  • 2002-06-14 CN CNB028098153A patent/CN1243539C/zh not_active Expired - Fee Related
  • 2002-06-14 TW TW091113044A patent/TWI317290B/zh active
  • 2002-06-14 KR KR1020037016223A patent/KR100861444B1/ko not_active IP Right Cessation
  • 2002-06-14 WO PCT/JP2002/005950 patent/WO2002102353A1/ja active Application Filing
• 2004
  • 2004-08-30 HK HK04106502A patent/HK1063727A1/xx not_active IP Right Cessation

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