WO2015056851A1 - Comprimé à dissolution orale contenant de l'aripiprazole, et son procédé de préparation - Google Patents

Comprimé à dissolution orale contenant de l'aripiprazole, et son procédé de préparation Download PDF

Info

Publication number
WO2015056851A1
WO2015056851A1 PCT/KR2014/001703 KR2014001703W WO2015056851A1 WO 2015056851 A1 WO2015056851 A1 WO 2015056851A1 KR 2014001703 W KR2014001703 W KR 2014001703W WO 2015056851 A1 WO2015056851 A1 WO 2015056851A1
Authority
WO
WIPO (PCT)
Prior art keywords
aripiprazole
disintegrating tablet
hydrophilic polymer
solid dispersion
weight
Prior art date
Application number
PCT/KR2014/001703
Other languages
English (en)
Korean (ko)
Inventor
배진건
김동욱
양윤희
홍혜숙
변상환
김경미
Original Assignee
주식회사 한독
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 주식회사 한독 filed Critical 주식회사 한독
Publication of WO2015056851A1 publication Critical patent/WO2015056851A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds

Definitions

  • the present invention relates to an aripiprazole-containing orally disintegrating tablet having improved elution and absorption, improved taste, foreign body feeling, and the like.
  • Aripiprazole a quinolinone derivative
  • Aripiprazole is an antipsychotic and is marketed under the trade name Abilify TM , for the treatment or amelioration of schizophrenia. It is administered for the treatment of acute mania and mixed episodes associated with bipolar disorder and for adjuvant therapy for major depressive disorder.
  • aripiprazole Depending on the use of hydrogen ions in the physical properties of aripiprazole, it is well eluted under acidic conditions but eluted under neutral to basic conditions.Aripiprazole is agglomerated in the process of manufacture and elution, resulting in content unevenness or storage. There is a problem that the dissolution rate during the fall. In order to improve this, dissolution aids of surfactants are generally used. However, in the case of a composition containing such a surfactant, oral disintegration tablets, such as taste is very bad, mouth feel is lowered, there is a fear of toxicity during long-term use, as a result it is difficult to use.
  • an object of the present invention is to provide an aripiprazole-containing orally disintegrating tablet having excellent dissolution, ensuring dissolution stability even during long-term storage, and excellent mouth feel such as taste and foreign body feeling.
  • the present invention is an orally disintegrating tablet (ODT) comprising aripiprazole as an active ingredient, the tablet comprises a solid dispersion of aripiprazole and a hydrophilic polymer, Tablets provide oral disintegrating tablets comprising a sugar alcohol.
  • ODT orally disintegrating tablet
  • a part of the sugar alcohol is contained in a solid dispersion of aripiprazole and a hydrophilic polymer.
  • the flowability of the prepared solid dispersion granules is significantly improved, so that the tableting machine filling efficiency is improved, and the filling deviation is small.
  • ODTs containing sugar alcohols in solid dispersions dissolve better in the oral cavity than ODTs without sugar alcohols in solid dispersions, resulting in much less foreign body feeling, and initial dissolution deviations between individual tablets. Is less.
  • Aripiprazole ODT of the present invention was able to improve the conventional problems of aripiprazole by introducing the above technical idea, and as a result, the orally disintegrating tablet of the present invention is substantially free of a surfactant that can cause various problems. It is preferable.
  • substantially free means including less than or equal to about 2% by weight, more preferably less than or equal to about 1% by weight, more preferably 0.2 It means to include up to weight percent, even more preferably means not to contain at all.
  • sugar alcohols may include mannitol, xylitol, sorbitol, maltitol, erythritol, or mixtures thereof, in particular for various purposes of the present invention.
  • Mannitol is preferred.
  • sorbitol and maltitol sticking occurs during tableting of oral disintegrating tablets, which makes them less suitable for mass production.
  • sorbitol and maltitol there is a concern that the solid dispersion has high moisture content and stability is not good, and in the case of aripiprazole oral disintegration tablets using maltitol, disintegration is relatively slow.
  • the content of sugar alcohol is preferably less than 3 parts by weight relative to 1 part by weight of aripiprazole, in consideration of dissolution stability, flowability, and the like. It is more preferable, and it is still more preferable that it is 0.5-2 weight part.
  • hydrophilic polymers for forming a solid dispersion include hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG). ), Polyvinyl alcohol (PVA), sodium-carboxymethyl cellulose (Na-CMC), Xantan Gum, polymethacrylate, starch, starch derivative or mixtures thereof may be used.
  • hydroxypropyl methyl cellulose HPMC
  • HPMC hydroxypropyl methyl cellulose
  • HPMC hydroxypropyl cellulose
  • HPMC hydroxypropyl cellulose
  • the viscosity of the hydrophilic polymer (particularly, hydroxypropylmethylcellulose (HPMC)) for forming such a solid dispersion is 2.5 to 10 cps when measured using a conventional polymer viscosity measuring instrument at 20 ° C. in a 2% by weight aqueous solution. It is preferable that it is 4-6 cps, and it is more preferable.
  • HPMC hydroxypropylmethylcellulose
  • the content of the hydrophilic polymer is preferably 0.3 to 0.04 parts by weight relative to 1 part by weight of aripiprazole, and 0.25 It is more preferable that it is -0.04 weight part, It is still more preferable that it is 0.16-0.06 weight part.
  • d (0.9) of the solid dispersion is 10 to 10. It is preferable that it is 50 micrometers, It is more preferable that it is 10-30 micrometers, It is more preferable that it is 10-25 micrometers. Moreover, it is preferable that d (0.5) of a solid dispersion is 5-20 micrometers, and it is more preferable that it is 5-10 micrometers.
  • Aripiprazole ODT according to the present invention may include various additives within the range not impairing the object of the present invention, in addition to the aforementioned components.
  • disintegrating agents such as low-substituted hydroxypropyl cellulose (L-HPC), crospovidone, croscarmellose sodium, starch, sodium starch glycolate, hydroxypropyl starch, microcrystalline cellulose;
  • Lubricants such as magnesium stearate, talc, sodium stearyl fumarate, calcium stearate, and silicon dioxide; Flavoring agents; coloring agent; It may further include an antioxidant and the like, but the present invention is not limited to these kinds of additional ingredients.
  • oral disintegrating tablets of the present invention for the purpose of the present invention, such as foreign body feeling, taking feeling, dissolution rate improvement, etc., except for the lubricant in the total weight of the oral disintegrating tablets 7% by weight, preferably 5% by weight or less, Preferably 3% by weight or less.
  • the three-component solid dispersion of the present invention for preparing orally disintegrating tablets is preferably substantially free of insoluble components.
  • the present invention also comprises the steps of preparing a solution or suspension containing (S1) aripiprazole, a hydrophilic polymer and a sugar alcohol (preferably mannitol); And (S2) spray-drying the solution or suspension, thereby preparing a solid dispersion, which provides a method for preparing orally disintegrating tablets containing aripiprazole, more preferably.
  • the process according to the invention further comprises the step of (S3) mixing the prepared solid dispersion with a sugar alcohol (preferably mannitol), followed by (S4) tableting such a mixture. do.
  • the content of sugar alcohol (preferably mannitol) to form a three-component solid dispersion is preferably less than 3 parts by weight relative to 1 part by weight of aripiprazole in consideration of dissolution stability, flowability, and the like. It is more preferable that it is 0.1-2.5 weight part, and it is still more preferable that it is 0.5-2 weight part.
  • the viscosity of the hydrophilic polymer (particularly, hydroxypropylmethylcellulose (HPMC)) for forming a three-component solid dispersion is a conventional polymer viscosity measuring instrument in a 2% by weight aqueous solution at 20 °C When measured using a 2.5 to 10 cps is preferred, and more preferably 4 to 6 cps.
  • the content of the hydrophilic polymer (particularly, HPMC) for forming a three-component solid dispersion is preferably 0.3 to 0.04 parts by weight, and 0.25 to 0.04 parts by weight based on 1 part by weight of aripiprazole. It is preferable and it is still more preferable that it is 0.16-0.06 weight part.
  • the spray drying may be carried out using a device such as a spray-dryer, a fluid-bed granulator commonly used in the field to which the present invention belongs, the manufacturing method of the present invention is such a specific device It is not limited to the kind of.
  • the spray drying method is preferable in the preparation of the three-component solid dispersion granules according to the present invention, and when the granules are manufactured by a general wet granulation method, the disintegration is slowed and the feeling of taking a deterioration is reduced due to a foreign body. have. It is understood that the size of the granules increases in the preparation of general wet granules, and that the larger granule size affects the melting rate, and thus, the disintegration rate of the tablet is decisively reduced compared to the method of preparing a solid dispersion of the spray drying method. This mechanism is not limited.
  • the present invention provides an aripiprazole-containing ODT having excellent absorption and dissolution rate and excellent mouth feel such as taste and foreign matter, and a method for producing the same.
  • 1 is a graph showing the dissolution rate improvement effect of the three-component solid dispersion according to the present invention.
  • Figure 2 is a graph showing the change in dissolution rate according to the polymer used as a binder in the three-component solid dispersion according to the present invention.
  • 3 is a dissolution graph showing the effect of the presence or absence of sugar alcohol on the dissolution rate of the tablet in the three-component solid dispersion according to the present invention.
  • Figure 4 is an elution graph showing the effect of the viscosity of the hydrophilic polymer used in the dissolution rate in the three-component solid dispersion according to the present invention.
  • a tablet containing aripiprazole was prepared as follows.
  • First Example 1 was prepared as follows. 72 g of D-mannitol and 8 g of HPMC were added to 600 g of water to dissolve. The resulting solution was suspended by adding 32 g of L-HPC and 24 g of aripiprazole while stirring with a mechanical stirrer. The resulting suspension was spray-dried using a spray dryer (Mini spray dryer, Buchi 290) at an inlet temperature of 130 to 135 ° C and an outlet temperature of 65 to 75 ° C to obtain a solid dispersion.
  • a spray dryer Mini spray dryer, Buchi 290
  • Example 2 was prepared as follows. 72 g of D-mannitol was added to 600 g of water to dissolve. The resulting solution was suspended by adding 32 g of L-HPC and 24 g of aripiprazole while stirring with a mechanical stirrer. Using the obtained suspension, a solid dispersion was obtained in the same manner as in Example 1. 104 g of solid dispersion, 652 g of D-mannitol, and 12 g of magnesium stearate were mixed and tableted at 100 mg weight per tablet using a single tablet tablet machine (Killian SP300) to prepare a tablet containing 3 mg of Aripiprazole.
  • Killian SP300 single tablet tablet machine
  • Example 3 was prepared as follows. Aripiprazole 24g, L-HPC 30g, D-mannitol 684g and magnesium stearate 12g were mixed and tableted at 100mg weight per tablet using a single tablet tablet (Killian SP300) to prepare a tablet containing 3mg of Aripiprazole.
  • Example 1-3 The dissolution rate of Example 1-3 was evaluated. Specifically, 900 ml of pH 5.0 sodium acetate buffer was used as the elution medium, and the paddle method (75 rpm) was used. The dissolution test results are shown in FIG. 1. As a positive control, Abilify TM OD containing 3 mg of aripiprazole, which is commercially available, was used.
  • a tablet containing aripiprazole was prepared as follows.
  • a tablet containing 24 mg of Aripiprazole was prepared by mixing solid dispersion 104 g, crospovidone 35 g, D-mannitol 205.8 g, and magnesium stearate 5.3 g, and then tableting at a 350 mg weight per tablet using a single tablet tablet (Killian SP300).
  • Example 4 Example 5
  • Example 6 Example 7
  • Example 8 HPMC 3cps HPMC 4.5cps HPC-L HPC-SL PVP-k30 mg / T mg / T mg / T mg / T mg / T API Aripiprazole 24.0 24.0 24.0 24.0 24.0 Excipient D-Mannitol 72.0 72.0 72.0 72.0 72.0 Binder HPMC 3cps 8.0 HPMC 4.5cps 8.0 HPC-L 8.0 HPC-SL 8.0 PVP-K30 8.0 Disintegrant Crospovidone 35.0 35.0 35.0 35.0 35.0 35.0 35.0 35.0 Excipient D-Mannitol 205.8 205.8 205.8 205.8 Lubricant Magnesium Stearate 5.3 5.3 5.3 5.3 5.3 5.3 5.3 5.3
  • Example 4-8 The dissolution rate of Example 4-8 was evaluated. Specifically, 900 ml of pH 5.0 sodium acetate buffer was used as the elution medium, and the paddle method (75 rpm) was used. The dissolution test results are shown in FIG. 2.
  • Particle diameters of the solid dispersions prepared in Examples 4-8 were measured, and the results are shown in Table 3 below. Helos (laser diffraction) instrument was used to measure the particle size. In the following d (0.1) means that 10% of the particles have a particle size distribution less than that size, d (0.5) means a particle size distribution of 50% of the particles below that size, d (0.9) is 90 This means that% has a particle size distribution below that size.
  • the size of the solid dispersion particles produced according to the type of the polymer used to form the solid dispersion was different, which had a great influence on the degree of foreign matter, which is an important physical property of the ODT.
  • the d (0.9) of the solid dispersion is preferably 10 to 50 ⁇ m, It is more preferable that it is 10-30 micrometers, and it is more preferable that it is 10-25 micrometers. Moreover, it is preferable that d (0.5) of a solid dispersion is 5-20 micrometers, and it is more preferable that it is 5-10 micrometers.
  • oral disintegrating tablets containing aripiprazole were prepared in the same or similar manner as in Example 1.
  • Example 10 (w / o mannitol in SD) (w mannitol in SD) mg / T mg / T Solid dispersion API Aripiprazole 24.0 24.0 Excipient D-Mannitol 48.0 Binder HPMC (4.5 cps) 2.0 2.0 Post-mix Disintegrant Crospovidone 10.5 10.5 Disintegrant HPS (Hydroxypropyl starch) 24.5 24.5 Excipient D-Mannitol 230.5 278.5 Lubricant Colloidal Silica dioxide 3.5 3.5 Lubricant Sodium Stearyl Fumarate 7.0 7.0
  • Example 10 Angle of repose value 48.37 ° 40.36 °
  • Example 10 including mannitol, which is a sugar alcohol, in preparation of the solid dispersion was much better than that of Example 9, whereby ODT was included in the solid dispersion. It can be seen that the filling efficiency is improved in tableting, etc., and the filling variation is reduced, thereby greatly improving the manufacturing efficiency.
  • ODT containing sugar alcohol in the solid dispersion was better dissolved in the oral cavity than ODT without sugar alcohol in the solid dispersion, and foreign body feeling was much reduced.
  • oral disintegrating tablets containing aripiprazole were prepared in the same or similar manner as in Example 1.
  • Table 6 (mg / T) Function Composition Example 11 12 13 14 15 Solid dispersion API Aripiprazole 24 24 24 24 24 24 Excipient D-Mannitol 120 72 48 24 0 Binder HPMC 645 (4.5 cps) 4 4 4 4 4 Post-mix Disintegrant Crospovidone 10.5 10.5 10.5 10.5 10.5 10.5 Disintegrant HPS 24.5 24.5 24.5 24.5 Excipient D-Mannitol 156.5 204.5 228.5 252.5 276.5 Lubricant Colloidal Silica dioxide 3.5 3.5 3.5 3.5 3.5 Lubricant Sodium Stearyl Fumarate 7.0 7.0 7.0 7.0 7.0 7.0 7.0
  • Example 11 to 15 The dissolution stability of Examples 11 to 15 was evaluated as follows, and the results are shown in Table 7 below. Specifically, as described above, the tablets were prepared and packaged in Alu-Alu, which is an excellent airtight packaging material, and stored at 60 ° C./80% RH for 2 weeks. Before and after the stability test, the sample was eluted by paddle method (75 rpm) using 900 ml of sodium acetate buffer pH 5.0 as the elution medium.
  • Example 11 12 13 14 15 Dissolution% at 15min (Initial) 93.2 89.1 89.6 85.6 89.2 Dissolution% at 15min (60 °C / 80% RH, 2 weeks) 53.0 73.0 88.7 88.3 88.8
  • the content of mannitol to 1 part by weight of aripiprazole is preferably less than 3 parts by weight, more preferably 0.1 to 2.5 parts by weight, and even more preferably 0.5 to 2 parts by weight.
  • oral disintegrating tablets containing aripiprazole were prepared in the same or similar manner as in Example 1.
  • Table 8 (mg / T) Function Composition Example 16 17 18 19 Solid dispersion API Aripiprazole 24 24 24 24 24 24 24 Excipient D-Mannitol 48 48 48 48 48 Binder HPMC 2 (3 cps) 2 (4.5 cps) 2 (6 cps) 2 (15 cps) Post-mix Disintegrant Crospovidone 10.5 10.5 10.5 10.5 Disintegrant HPS 24.5 24.5 24.5 24.5 Excipient D-Mannitol 230.5 230.5 230.5 230.5 230.5 Lubricant Colloidal Silica dioxide 3.5 3.5 3.5 3.5 Lubricant Sodium Stearyl Fumarate 7.0 7.0 7.0 7.0 7.0
  • the viscosity of the HPMC is the viscosity measured by 2% by weight aqueous solution at 20 °C.
  • Oral disintegration time (seconds) of the oral disintegrating tablets prepared in Examples 16 to 19 was measured and shown in Table 9 below.
  • Example 16 to 18 The dissolution results of Examples 16 to 18 are shown in FIG. 4. Dissolution test was carried out in the same manner as in Example 9. As shown in FIG. 4, when the viscosity of HPMC used to form the solid dispersion is less than 3 cps, the dissolution rate improvement effect was lowered.
  • the viscosity of the hydrophilic polymer (particularly, hydroxypropylmethylcellulose (HPMC)) for forming a solid dispersion is 2 wt% aqueous solution at 20 ° C. using a conventional polymer viscosity measuring instrument. In the case of measurement, it is preferable that it is 2.5 to 10 cps, more preferably 4 to 6 cps.
  • oral disintegrating tablets containing aripiprazole were prepared in the same or similar manner as in Example 1.
  • Table 10 (mg / T) Function Composition Example 20 21 22 23 Solid dispersion API Aripiprazole 24 24 24 24 24 Excipient D-Mannitol 48 48 48 48 48 Binder HPMC (4.5 cps) 8 4 3 2 Post-mix Disintegrant Crospovidone 10.5 10.5 10.5 10.5 Disintegrant HPS 24.5 24.5 24.5 24.5 Excipient D-Mannitol 224.5 228.5 229.5 230.5 Lubricant Colloidal Silica Dioxide 3.5 3.5 3.5 3.5 Lubricant Sodium Stearyl Fumarate 7.0 7.0 7.0 7.0 7.0
  • the viscosity of the HPMC is the viscosity measured by 2% by weight aqueous solution at 20 °C.
  • Intraoral disintegration time (seconds) and tablet hardness of the oral disintegrating tablets prepared in Examples 20 to 23 were measured and shown in Table 11 below.
  • the content of the hydrophilic polymer is 0.3 to 0.04 parts by weight relative to 1 part by weight of aripiprazole. It is preferable, It is more preferable that it is 0.25-0.04 weight part, It is still more preferable that it is 0.16-0.06 weight part.
  • oral disintegrating tablets containing aripiprazole were prepared in the same or similar manner as in Example 1.
  • Table 12 (mg / T) Function Composition Example 24 25 26 27 Solid dispersion API Aripiprazole 24 24 24 24 Excipient Sugar alcohol Mannitol 24 Sorbitol24 Maltitol 24 Microcrystalline cellulose 24 Binder HPMC (4.5 cps) 2 2 2 2 2 Post-mix Disintegrant Crospovidone 10.5 10.5 10.5 10.5 Disintegrant HPS 24.5 24.5 24.5 24.5 Excipient D-Mannitol 254.5 254.5 254.5 254.5 254.5 Lubricant Colloidal Silica Dioxide 3.5 3.5 3.5 3.5 Lubricant Sodium Stearyl Fumarate 7.0 7.0 7.0 7.0 7.0
  • the viscosity of the HPMC is the viscosity measured by 2% by weight aqueous solution at 20 °C.
  • the solid dispersion using sorbitol and maltitol had a high L.O.D.
  • the particle size was large and aggregates were formed, which resulted in poor mixing in the post-mixing process and caused a foreign body feeling when taken, giving a poor feeling of taking.
  • disintegration was slow.
  • the orally disintegrating tablet of the present invention contains 7% by weight or less, preferably 5% by weight or less, more preferably 3% by weight or less of the insoluble component relative to the total weight of the oral disintegrating tablet.
  • the three-component solid dispersion of the present invention for preparing orally disintegrating tablets is preferably substantially free of insoluble components.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Physiology (AREA)
  • Neurology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Psychiatry (AREA)
  • Biomedical Technology (AREA)
  • Nutrition Science (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

La présente invention concerne un comprimé à dissolution orale contenant de l'aripiprazole, qui utilise de l'aripiprazole et une dispersion solide d'un polymère hydrophile et, de préférence, utilise de l'aripiprazole et une dispersion solide à trois composants d'un polymère hydrophile spécifique et d'un alcool de sucre (de préférence, le mannitol). Le comprimé à dissolution orale contenant de l'aripiprazole selon la présente invention a une dissolution et une absorption améliorées et a une excellente sensation de goût lorsqu'il est avalé, et n'a pas aucune gêne causée par des corps étrangers.
PCT/KR2014/001703 2013-10-18 2014-02-28 Comprimé à dissolution orale contenant de l'aripiprazole, et son procédé de préparation WO2015056851A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2013-0124368 2013-10-18
KR20130124368 2013-10-18

Publications (1)

Publication Number Publication Date
WO2015056851A1 true WO2015056851A1 (fr) 2015-04-23

Family

ID=51749921

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2014/001703 WO2015056851A1 (fr) 2013-10-18 2014-02-28 Comprimé à dissolution orale contenant de l'aripiprazole, et son procédé de préparation

Country Status (3)

Country Link
JP (1) JP5764688B2 (fr)
KR (1) KR101428018B1 (fr)
WO (1) WO2015056851A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7211136B2 (ja) * 2019-02-14 2023-01-24 ニプロ株式会社 錠剤、および、その製造方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060078609A1 (en) * 2002-11-29 2006-04-13 Vandecruys Roger P G Pharmaceutical compositions comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water soluble and respectively base
KR20100138768A (ko) * 2009-06-25 2010-12-31 (주)차바이오앤디오스텍 불쾌한 맛을 효과적으로 은폐한 경구용 속용 필름
US20110311626A1 (en) * 2009-02-23 2011-12-22 Gopi Venkatesh Controlled release compositions comprising anti-cholinergic drugs
US20120214820A1 (en) * 2009-09-15 2012-08-23 Ratiopharm Gmbh Orally disintegrating pharmaceutical dosage form containing aripiprazole
US8545890B2 (en) * 2006-03-31 2013-10-01 Rubicon Research Private Limited Orally disintegrating tablets

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001095941A1 (fr) * 2000-06-14 2001-12-20 Nippon Shinyaku Co., Ltd. Dispersions solides et medicaments
ES2855426T3 (es) * 2008-09-17 2021-09-23 Mylan Inc Granulados, proceso de preparación de los mismos y productos farmacéuticos que los contienen

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060078609A1 (en) * 2002-11-29 2006-04-13 Vandecruys Roger P G Pharmaceutical compositions comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water soluble and respectively base
US8545890B2 (en) * 2006-03-31 2013-10-01 Rubicon Research Private Limited Orally disintegrating tablets
US20110311626A1 (en) * 2009-02-23 2011-12-22 Gopi Venkatesh Controlled release compositions comprising anti-cholinergic drugs
KR20100138768A (ko) * 2009-06-25 2010-12-31 (주)차바이오앤디오스텍 불쾌한 맛을 효과적으로 은폐한 경구용 속용 필름
US20120214820A1 (en) * 2009-09-15 2012-08-23 Ratiopharm Gmbh Orally disintegrating pharmaceutical dosage form containing aripiprazole

Also Published As

Publication number Publication date
JP2015091769A (ja) 2015-05-14
JP5764688B2 (ja) 2015-08-19
KR101428018B1 (ko) 2014-08-12

Similar Documents

Publication Publication Date Title
JP5171259B2 (ja) プロトンポンプインヒビターを包含する固形剤形およびそれから調製された懸濁剤
CA2430829C (fr) Comprime a desintegration rapide comprenant un ingredient actif acido-labile
WO2013054872A1 (fr) COMPRIMÉ COMPRENANT DE LA 7-[4-(4-BENZO[ｂ]THIOPHÈN-4-YL-PIPÉRAZIN-1-YL) BUTOXY]-1H-QUINOLIN-2-ONE OU UN SEL DE CELLE-CI
AU2010285740A1 (en) Quinoline derivative-containing pharmaceutical composition
JP2004514733A (ja) 酸分解性活性成分を含有するペースト形の医薬品製造物
WO2015199356A1 (fr) Formulation composite pour administration par voie orale comprenant de l'ézétimibe et de la rosuvastatine et procédé de préparation associé
WO2019004770A9 (fr) Composition pour préparation solide à usage oral comprenant un inhibiteur de pompe à protons, préparation solide à usage oral la comprenant, et son procédé de préparation
JP2006298811A (ja) ゲル化抑制製剤の設計
EP2988727B1 (fr) Composition pharmaceutique comprenant un agent antipsychotique atypique et procédé de préparation correspondant
WO2019066555A1 (fr) Composition pharmaceutique comprenant un comprimé sphéroïdal à unités multiples contenant de l'ésoméprazole et un sel de qualité pharmaceutique de celui-ci, et procédé de préparation de la composition pharmaceutique
WO2015056851A1 (fr) Comprimé à dissolution orale contenant de l'aripiprazole, et son procédé de préparation
CN110404079B (zh) 一种不含碳酸盐、低基因毒性杂质含量的喹啉衍生物或其盐的药物组合物
WO2013157841A1 (fr) Comprimé à libération prolongée contenant de la lévodropropizine et procédé pour préparer celui-ci
WO2021002588A1 (fr) Composition pharmaceutique contenant de la tamsulosine ou un chlorhydrate de tamsulosine et procédé de préparation associé
WO2021091188A1 (fr) Composition pharmaceutique à libération prolongée pour une administration orale, contenant du rebamipide ou un sel pharmaceutiquement acceptable de celui-ci
JP6336078B2 (ja) 医薬組成物
WO2016052945A1 (fr) Granulés contenant de l'oseltamivir, capsules comprenant les granulés et procédé de préparation des capsules
JP2023513045A (ja) 非晶質ニロチニブ微粒子及びその使用
WO2018203636A1 (fr) Composition ayant une solubilité dans l'eau et une biodisponibilité améliorées
JP3597823B2 (ja) 固形製剤
KR101578627B1 (ko) 실로도신의 용출 특성이 향상된 약제학적 제제
WO2018101681A1 (fr) Comprimé composite oral comprenant de l'ézétimibe et de la rosuvastatine
KR102512866B1 (ko) 아프레피탄트의 용해도가 증가된 경구용 조성물
WO2016144071A2 (fr) Formulations pharmaceutiques comprenant du rivaroxaban
CN111840233B (zh) 一种孟鲁司特钠固体分散体、其制备方法及其应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14854454

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14854454

Country of ref document: EP

Kind code of ref document: A1