JP2022030576A - Storage method of linagliptin hydrate-containing preparation, linagliptin hydrate-containing preparation and evaluation method stored by that method - Google Patents

Abstract

To provide methods for storing a linagliptin hydrate-containing formulation in which linagliptin hydrate maintains Form C after production, or to provide linagliptin hydrate-containing formulations stored by the storage method, and further to provide methods for evaluating that the linagliptin hydrate contained in the linagliptin hydrate-containing formulation maintains Form C.SOLUTION: According to one embodiment of the present invention, there is provided a method for storing a linagliptin hydrate-containing formulation, which maintains an equilibrium relative humidity of the linagliptin hydrate-containing formulation in terms of 25°C of 10% or more and 45% or less.SELECTED DRAWING: Figure 1

Description

The present invention relates to a storage method of a linagliptin hydrate-containing preparation, a linagliptin hydrate-containing preparation stored by the method, and an evaluation method.

Linagliptin (1-[(4-methyl-quinazoline-2-yl) methyl] -3-methyl-7- (2-butin-1-yl) -8- (3- (R) -amino-piperidine-1-) Il) -xanthine) is a dipeptidyl peptidase-4 (DPP-IV) inhibitor and is used as a therapeutic agent for type II diabetes. Patent Document 1 describes linagliptin or a salt thereof, a first diluent which is mannitol, a second diluent which is pregelatinized starch, a binder which is copovidone, a tablet decomposition substance which is corn starch, and magnesium stearate. A pharmaceutical composition comprising a certain lubricant is disclosed.

Further, it is known that polymorphs A, B, C, D and E are present in linagliptin crystals (Patent Document 2). Linagliptin hydrate is polymorph C (Form C), but Form C is heated to a temperature of 30 ° C to 100 ° C and dried at this temperature to form polymorph D (Form D), which is an anhydride. It is known to be. It is also known that Form D is transferred to the anhydrous polymorph E (Form E) and further from Form E to the anhydrous polymorph A (Form A) under high temperature conditions.

Patent No. 5478244 Patent No. 5323684

One of the objects of the present invention is to provide a method for storing a linagliptin hydrate-containing preparation in which linagliptin hydrate maintains a hydrated state after production. Alternatively, one embodiment of the present invention aims to provide a linagliptin hydrate-containing preparation stored by the storage method thereof. Alternatively, one embodiment of the present invention aims to provide a method for evaluating that the hydrated form of linagliptin contained in the linagliptin hydrate-containing preparation is maintained.

According to one embodiment of the present invention, there is provided a method for storing a linagliptin hydrate-containing preparation, which maintains an equilibrium relative humidity of the linagliptin hydrate-containing preparation at 25 ° C. of 10% or more and 45% or less.

In the storage method, it is preferable that the equilibrium relative humidity is maintained for one month or more.

In the storage method, the linagliptin hydrate-containing preparation is contained in a first package, the first package is sealed by a second package together with a desiccant, and the first package is a PTP packaging sheet. , The second package may be a pillow package.

According to one embodiment of the present invention, there is provided a linagliptin hydrate-containing preparation having an equilibrium relative humidity of 10% or more and 45% or less in terms of 25 ° C. of the linagliptin hydrate-containing preparation.

It is preferable that the equilibrium relative humidity is maintained in the linagliptin hydrate-containing preparation.

In the linagliptin hydrate-containing preparation, the linagliptin hydrate-containing preparation may be contained in the first package, and the first package may be sealed by the second package.

The first package may be sealed by the second package together with the desiccant.

The first package may be a PTP package sheet and the second package may be a pillow package.

According to one embodiment of the present invention, after storing the linagliptin hydrate-containing preparation for one month from the production, the equilibrium relative humidity converted to 25 ° C. of the linagliptin hydrate-containing preparation is measured, and the equilibrium relative humidity is 10% or more. A method for evaluating a linagliptin hydrate-containing preparation, which determines that the linagliptin contained in the linagliptin hydrate-containing preparation maintains the hydrate when the content is 45% or less, is provided.

According to one embodiment of the present invention, there is provided a method for storing a linagliptin hydrate-containing preparation in which the linagliptin hydrate maintains the hydrated form after production. Alternatively, according to one embodiment of the present invention, a linagliptin hydrate-containing preparation stored by the storage method thereof is provided. Alternatively, according to one embodiment of the present invention, there is provided a method for evaluating that the linagliptin hydrate contained in the linagliptin hydrate-containing preparation maintains the hydrated form.

(A) is a schematic diagram showing the linagliptin hydrate-containing pharmaceutical product package 100, and (b) is a schematic diagram showing the linagliptin hydrate-containing pharmaceutical product 10 contained in the PTP packaging sheet 101.

Hereinafter, the storage method of the linagliptin hydrate-containing preparation according to the present invention, the linagliptin hydrate-containing preparation stored by the method, and the evaluation method will be described in detail. However, the storage method of the linagliptin hydrate-containing preparation of the present invention, the linagliptin hydrate-containing preparation and the evaluation method stored by the method are interpreted only as described in the embodiments and examples shown below. It's not something.

It is known that linagliptin hydrate (Form C) is desorbed from hydrated water and transferred to anhydrous water (Form D) under high temperature and low humidity. For the first time, the present inventors have found that in order for linagliptin contained in a Japanese product-containing preparation to maintain its hydrated form, it is necessary not only to prevent the linagliptin hydrate-containing preparation from drying out, but also to prevent a humid state. rice field. More specifically, the present inventors have found for the first time that the hydrated form of linagliptin is maintained by maintaining the equilibrium relative humidity converted to 25 ° C. at 10% or more and 45% or less. The transfer of linagliptin hydrate to anhydrate under humid conditions has not been previously known and has been newly discovered by the present inventors.

Here, the "equilibrium relative humidity" is the relative humidity in a state where the hygroscopic substance does not exchange water with the surrounding environment.

According to one embodiment of the present invention, in the linagliptin hydrate-containing preparation, linagliptin water is maintained by maintaining the equilibrium relative humidity converted to 25 ° C. at 10% or more and 45% or less, preferably 12% or more and 32% or less. The hydrated form of linagliptin contained in the Japanese-containing preparation can be maintained.

[Storage method of linagliptin hydrate-containing preparation]
FIG. 1 is a schematic view showing a storage method of a linagliptin hydrate-containing preparation according to an embodiment of the present invention. FIG. 1A is a schematic view showing a linagliptin hydrate-containing pharmaceutical product package 100. Further, FIG. 1 (b) is a schematic view showing the linagliptin hydrate-containing preparation 10 contained in the PTP packaging sheet 101. In one embodiment, the linagliptin hydrate-containing pharmaceutical product 10 is contained in the PTP packaging sheet 101. Based on the conventional finding that the hydrated form of linagliptin cannot be maintained by drying, it should be possible to maintain Form C by sealing the PTP packaging sheet 101 with pillow packaging 103. Good packaging may not be sufficient to maintain the hydrated form of linagliptin.

Since the pillow package 103 has an excellent sealing property, the water content inside the pillow package 103 can be kept substantially constant during the storage period. Therefore, when the PTP packaging sheet 101 is sealed with the pillow packaging 103 (initials), the equilibrium relative humidity converted to 25 ° C. in the space inside the pillow packaging 103 when the steady state is reached is 10% or more and 45%. Hereinafter, it is preferably 12% or more and 32% or less. That is, the water content of the space inside the pillow packaging 103 at the time when the PTP packaging sheet 101 is sealed with the pillow packaging 103 (initial) is the water content of the linagliptin hydrate-containing preparation 10 itself and the PTP packaging sheet 101. It is affected by the humidity of the work environment sealed with the pillow package 103. Therefore, when the PTP packaging sheet 101 is sealed with the pillow packaging 103, the equilibrium relative humidity converted to 25 ° C. in the space inside the pillow packaging 103 that has reached a steady state is 10% or more and 45% or less, preferably 12%. In order to make it 32% or less, it is necessary to adjust the water content of the linagliptin hydrate-containing preparation 10 itself and the humidity of the working environment for sealing the PTP packaging sheet 101 with the pillow packaging 103.

In the present embodiment, the equilibrium relative humidity of the linagliptin hydrate-containing preparation 10 converted to 25 ° C. is maintained at 10% or more and 45% or less. Therefore, due to the linagliptin hydrate-containing preparation 10 controlled to an appropriate water content and the working environment controlled to an appropriate humidity, the PTP packaging sheet, which is the first package in the linagliptin hydrate-containing preparation package 100, is used. The 101 is sealed by the pillow package 103, which is the second package. At this time, the desiccant 105 may be enclosed together. The desiccant 105 absorbs the water content of the linagliptin hydrate-containing preparation 10 when the water content of the linagliptin hydrate-containing preparation 10 is high or when the humidity in the PTP packaging sheet 101 is high. The equilibrium relative humidity of the space inside the package 103 converted to 25 ° C. can be maintained at 10% or more and 45% or less. In the present embodiment, the space in the second package 103 that has reached a steady state by sealing the first package 101 or by sealing the first package 101 together with the desiccant 105. The equilibrium relative humidity converted to 25 ° C. can be maintained at 10% or more and 45% or less. As a result, the equilibrium relative humidity of the space in the first package 101 that has reached a steady state in terms of 25 ° C. is also maintained at 10% or more and 45% or less, and the linagliptin hydrate-containing preparation 10 that has reached a steady state. The equilibrium relative humidity converted to 25 ° C. can be maintained at 10% or more and 45% or less. The linagliptin hydrate-containing pharmaceutical package 100 may be housed in, for example, a paper box, or may be stored and distributed in a state where the paper box is further covered with a vinyl film.

As the PTP packaging sheet 101 and the pillow packaging 103, known PTP packaging sheets and pillow packaging can be used, respectively. The PTP packaging sheet 101 may be, for example, a sheet in which a film selected from polyvinyl chloride film, polyvinylidene chloride film, polychlorotrifluoroethylene film, and polypropylene is composited. Further, the pillow packaging 103 may be an aluminum pillow.

As the desiccant 105, a known desiccant used as a desiccant for pharmaceutical products can be used. For example, it can be selected from calcium chloride (for example, ID (registered trademark) sheet of ID Co., Ltd.) and oxygen scavenger (for example, Pharmakeep (registered trademark) of Mitsubishi Gas Chemical Company, Inc.).

When the desiccant 105 is enclosed in the pillow package 103, the equilibrium relative humidity is determined by the hygroscopic force of the desiccant. When the desiccant 105 is not used, the relative humidity in the pillow is determined by the environmental humidity in the controlled working environment of the pillow packaging. The relationship between the control of equilibrium relative humidity for maintaining the hydrated form of linagliptin and the packaging form has not been investigated so far, and water of linagliptin is watered by maintaining the equilibrium relative humidity at 45% or less. The ability to maintain the Japanese form is a surprising effect that cannot be predicted from conventional findings.

The linagliptin hydrate-containing preparation 10 according to the present embodiment uses such a packaging form to reduce the equilibrium relative humidity of the linagliptin hydrate-containing preparation 10 at 25 ° C. to 10% or more and 45% or less. It can be maintained for more than a month. The equilibrium relative humidity can be maintained in the above range, preferably for 3 months or longer, more preferably for 6 months or longer. Therefore, the linagliptin hydrate-containing preparation 10 according to the present embodiment can maintain the hydrated form of linagliptin for 1 month or longer, preferably 3 months or longer, more preferably 6 months or longer.

[Linagliptin hydrate-containing preparation]
The linagliptin hydrate-containing preparation 10 according to the present embodiment may be a known preparation containing linagliptin hydrate having a Form C crystal structure. The linagliptin hydrate-containing preparation 10 may contain, for example, 5 mg of linagliptin hydrate having a crystal structure of Form C as linagliptin per tablet, but the content is not limited to this and is an effective amount for treatment. All you need is. The crystal structure of linagliptin hydrate shall be determined by the powder X-ray diffraction measurement method.

In one embodiment, the linagliptin hydrate-containing preparation 10 according to the present embodiment may contain a pharmaceutically acceptable excipient, a binder, a disintegrant and a lubricant. Excipients include, for example, lactose hydrate, anhydrous lactose, crystalline cellulose, powdered cellulose, dicalcium phosphate anhydride, dicalcium dihydrate dihydrate, erythritol, low-substituted hydroxypropyl cellulose (L-HPC), and the like. One or more selected from the group consisting of mannitol, corn starch, partially pregelatinized starch and xylitol can be used, but is not limited thereto. In one embodiment, when the linagliptin hydrate-containing preparation is 100% by mass, an excipient of 3% by mass or more and 88% by mass or less can be contained.

Binders include, for example, copovidone (complex of vinylpyrrolidone and other vinyl derivatives), hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), polyvinylpyrrolidone (povidone), polyvinyl alcohol (PVA), partially pregelatinized starch. And, but not limited to, one or more selected from the group consisting of L-HPC can be used. In one embodiment, when the linagliptin hydrate-containing preparation is 100% by mass, a binder of 1% by mass or more and 5% by mass or less can be contained.

As the disintegrant, for example, one or more selected from the group consisting of corn starch, crospovidone, croscarmellose sodium, carmellose calcium, carmellose, sodium starch glycolate, L-HPC and partially pregelatinized starch is used. However, it is not limited to these. In one embodiment, when the linagliptin hydrate-containing preparation is 100% by mass, a disintegrant of 5% by mass or more and 15% by mass or less can be contained.

The lubricant is selected from the group consisting, for example, talc, macrogol (PEG), calcium behenate, calcium stearate, sucrose fatty acid ester, stearyl sodium fumarate, stearic acid, hydrogenated castor oil and magnesium stearate. One or more of them can be used, but the present invention is not limited to these. In one embodiment, when the linagliptin hydrate-containing preparation is 100% by mass, a lubricant of 0.1% by mass or more and 4% by mass or less can be contained.

Further, in one embodiment, the linagliptin hydrate-containing preparation 10 may be a tablet, a film-coated tablet or a capsule. In film-coated tablets, the coating film may contain a film substrate, a plasticizer, a lubricant and optionally one or more colorants. As the film substrate, for example, HPMC can be used, but the film substrate is not limited thereto. Further, as the plasticizer, for example, macrogol can be used, but the plasticizer is not limited to this. As the plasticizer, for example, talc and titanium dioxide can be used, but the plasticizer is not limited thereto. As the colorant, for example, iron oxide can be used, but the colorant is not limited thereto. When the film-coated tablet is 100% by mass, a coating film of 2% by mass or more and 4% by mass or less can be contained.

The linagliptin hydrate-containing preparation 10 according to the present embodiment can be produced by using a known production method. For example, a direct tableting method or a wet granulation method can be used. As the wet granulation method, for example, a stirring granulation method or a fluidized bed granulation method can be used.

The linagliptin hydrate-containing preparation 10 according to the present embodiment maintains the hydrated form of linagliptin by maintaining the equilibrium relative humidity converted to 25 ° C. at 10% or more and 45% or less. Therefore, as described above, the linagliptin hydrate-containing pharmaceutical product 10 is contained in the PTP packaging sheet 101 and sealed by the second packaging 103. At this time, the desiccant 105 may be enclosed together. Further, the linagliptin hydrate-containing pharmaceutical package 100 may be housed in, for example, a paper box, or may be stored and distributed in a state where the paper box is further covered with a vinyl film.

The linagliptin hydrate-containing preparation 10 according to the present embodiment maintains an equilibrium relative humidity of 10% or more and 45% or less at 25 ° C. for 1 month or longer, preferably 3 months or longer, and more preferably 6 months or longer. .. Therefore, the linagliptin hydrate-containing preparation 10 according to the present embodiment can maintain the hydrated form of linagliptin for 1 month or longer, preferably 3 months or longer, more preferably 6 months or longer.

[Evaluation method of linagliptin hydrate-containing preparation]
As described above, the linagliptin hydrate-containing preparation 10 according to the present embodiment maintains the hydrated form of linagliptin by maintaining the equilibrium relative humidity converted to 25 ° C. at 10% or more and 45% or less. To. From this finding, it is possible to evaluate whether or not the hydrated form of linagliptin is maintained by measuring the equilibrium relative humidity of the linagliptin hydrate-containing preparation 10 converted to 25 ° C.

Specific examples and test results according to the present invention described above will be shown and described in detail.

[Manufacturing of linagliptin hydrate-containing preparation]
A linagliptin hydrate-containing preparation was produced by direct tableting or a wet granulation method. Specifically, linagliptin hydrate (Form C) 5.0 g, D-mannitol (Granutol® F, Freund Sangyo Co., Ltd.) 130.9 g, partially pregelatinized starch (Starch 1500 G®, corn). 18.0 g of corn starch (Nihon Shokuhin Kako Co., Ltd.) and 5.4 g of copovidone (KOLLIDON (registered trademark) VA64, BASF) are sieved with a 30-mesh sieve for 5 minutes in a plastic bag. Mixed. 2.7 g of magnesium stearate (Plant, Taihei Kagaku Sangyo Co., Ltd.) was added to the mixture, and the mixture was mixed for 1 minute. The obtained mixture was compression-molded using a rotary tableting machine to produce tablets.

Hypromerose (TC-5 (registered trademark) M, Shin-Etsu Chemical Industry Co., Ltd.) 100.0 g, Macrogor 6000 (Nichiyu Co., Ltd.) 10.0 g, Tarku (Fuji Taruku Kogyo Co., Ltd.) 35.0 g, Titanium oxide (NA61) , Toho Titanium Co., Ltd.) 50.0 g and iron sesquioxide (Shinmi Kasei Co., Ltd.) 5.0 g were stirred, dissolved and dispersed in 1150.0 g of purified water using a mixer to prepare a film coating liquid. The produced tablets were coated with a film coating solution until the mass per tablet increased by about 5 mg to produce film-coated tablets (formulation 1).

5.4 g of copovidone (KOLLIDON (registered trademark) VA64, BASF) was dissolved in 30.6 g of purified water to produce a granulation solution. Linagliptin hydrate (Form C) 5.0 g, D-mannitol (25C, ROQUETTE) 130.9 g, partially pregelatinized starch (Starch 1500 G (registered trademark), Colorcon) 18.0 g and corn starch (Nihon Shokuhin Kako) Co., Ltd.) 18.0 g was mixed using a starch dairy pot. The mixture was moistened with a granulation solution and then granulated. The granulated product was dried at 60 ° C. in a dryer so that the drying weight loss value was 5% or less. After sizing the dried product with a 30-mesh sieve, 2.7 g of magnesium stearate (Plant, Taihei Kagaku Sangyo Co., Ltd.) was added, and the mixture was mixed in a plastic bag for 1 minute. The obtained mixture was compression-molded using a rotary tableting machine to produce tablets. Using the obtained tablets, a film-coated tablet was produced by the same film-coating method as that for the pharmaceutical product 1 (pharmaceutical 2).

The pharmaceutical product 1 and the pharmaceutical product 2 were individually wrapped in a PTP packaging sheet. In addition, a sample in which the PTP packaging sheet is sealed in pillow packaging, a sample in which Pharmakeep (registered trademark) (Mitsubishi Gas Chemical Co., Ltd.) is sealed in pillow packaging together with the PTP packaging sheet, and an ID sheet (ID Co., Ltd.) together with the PTP packaging sheet. ) Was sealed in a pillow package, and a sample in which synthetic zeolite (Tokai Chemical Industry Co., Ltd.) was sealed in a pillow package together with a PTP packaging sheet was prepared.

Each sample was stored at 40 ° C. and 75% relative humidity, or 25 ° C. and 75% relative humidity for 1 month, 3 months or 6 months.

[Evaluation of crystal stability]
The crystal structure of each sample after storage was evaluated by the powder X-ray diffraction measurement method. The evaluation results of the pharmaceutical product 1 are shown in Table 1. The evaluation results of the pharmaceutical product 2 are shown in Table 2. In the table below, Form A and Form D show the crystal structure of linagliptin anhydride, and Form C shows the crystal structure of linagliptin hydrate.

From the results shown in Tables 1 and 2, in the sample containing only PTP packaging under the conditions of 40 ° C. and 75% relative humidity, transfer to the anhydride (Form A) was observed for both the pharmaceutical product 1 and the pharmaceutical product 2. From this result, it was clarified that the hot and humid environment transfers linagliptin hydrate to anhydrous. On the other hand, in the samples of PTP + pillow packaging, PTP + Pharmakeep (registered trademark) + pillow packaging and PTP + ID sheet + pillow packaging, both pharmaceutical product 1 and pharmaceutical product 2 are stored under the conditions of 40 ° C. and 75% relative humidity for 6 months. It maintained the hydrated form. However, in the sample packaged with PTP + zeolite + pillow, transfer to anhydrous (Form D) was observed by dehydration with zeolite.

[Equilibrium relative humidity measurement of linagliptin hydrate-containing preparation]
The equilibrium relative humidity of the linagliptin hydrate-containing preparation was measured using a water content measuring device (HYGROLAB) manufactured by Rotronic. Ten tablets of each sample stored under the above conditions were placed in a sample cup, set in a measurement chamber, and measured at room temperature. The measured equilibrium relative humidity was converted to 25 ° C. The evaluation results of the pharmaceutical product 1 are shown in Table 3. The evaluation results of the pharmaceutical product 2 are shown in Table 4.

From the results in Tables 3 and 4, there is almost no difference in the equilibrium relative humidity of the linagliptin hydrate-containing preparation when stored under the conditions of 25 ° C and 75% relative humidity and when stored under the conditions of 40 ° C and 75% relative humidity. I was not able to admit. In addition, the equilibrium relative humidity of the linagliptin hydrate-containing preparation was considered to reach a steady state after storage for one month. It was revealed that the equilibrium relative humidity of the linagliptin-containing preparation was also significantly higher in the sample containing only the PTP package in which the transfer to the anhydride (Form A) was observed. It was also revealed that the equilibrium relative humidity of the linagliptin-containing preparation was significantly lower in the PTP + zeolite + pillow packaged sample in which the transfer to anhydrous (Form D) was observed.

In the sample in which the preparation 1 produced by the fluidized bed granulation method was packaged in PTP + pillow, the equilibrium relative humidity of the linagliptin hydrate-containing preparation was reduced to 45% or less when stored at 40 ° C. and a relative humidity of 75% for 6 months. It became clear to maintain. Therefore, by controlling the humidity of the working environment during pillow packaging and setting the equilibrium relative humidity in the pillow packaging to 45% or less, linagliptin can be maintained in the hydrated form even when stored for a long period of time. .. In addition, in the sample in which the pharmaceutical product 1 produced by the fluidized bed granulation method was packaged in PTP + ID sheet + pillow, the equilibrium relative humidity of the linagliptin hydrate-containing pharmaceutical product was measured when stored for 6 months at 40 ° C. and 75% relative humidity. It became clear that it was maintained at 10% or more. Therefore, by enclosing the desiccant together and controlling the humidity, the equilibrium relative humidity in the pillow package can be set to 10% or more, and linagliptin can be maintained in the hydrated form even when stored for a long period of time. From the above results, in order to maintain the hydrated form of linagliptin under the temperature condition of 25 ° C to 40 ° C, the equilibrium relative humidity of the linagliptin hydrate-containing preparation is 10% or more and 45% or less (25 ° C conversion). It became clear that it was necessary to control the humidity.

Of course, other effects different from the effects brought about by the embodiments described above, which are obvious from the description of the present specification or which can be easily predicted by those skilled in the art, will naturally occur. It is understood that it is brought about by the present invention.

10 linagliptin hydrate-containing formulation, 100 linagliptin hydrate-containing formulation package, 101 first package, 103 second package, 105 desiccant

Claims (9)

A method for storing a linagliptin hydrate-containing preparation, which maintains an equilibrium relative humidity of the linagliptin hydrate-containing preparation at 25 ° C. at 10% or more and 45% or less. The method for storing a linagliptin hydrate-containing preparation according to claim 1, wherein the equilibrium relative humidity is maintained for one month or longer. The linagliptin hydrate-containing preparation is contained in the first package.
The first package is sealed by the second package together with the desiccant.
The method for storing a linagliptin hydrate-containing preparation according to claim 1 or 2, wherein the first package is a PTP package sheet and the second package is a pillow package. A linagliptin hydrate-containing preparation having an equilibrium relative humidity of 10% or more and 45% or less in terms of 25 ° C. of the linagliptin hydrate-containing preparation. The linagliptin hydrate-containing preparation according to claim 4, which maintains the equilibrium relative humidity. The linagliptin hydrate-containing preparation is contained in the first package.
The linagliptin hydrate-containing preparation according to claim 4 or 5, wherein the first package is sealed by the second package. The linagliptin hydrate-containing preparation according to claim 6, wherein the first package is sealed by the second package together with a desiccant. The linagliptin hydrate-containing preparation according to claim 6 or 7, wherein the first package is a PTP package sheet and the second package is a pillow package. After storing the linagliptin hydrate-containing preparation for one month from the production, the equilibrium relative humidity converted to the linagliptin hydrate-containing preparation at 25 ° C. was measured.
A method for evaluating a linagliptin hydrate-containing preparation, which determines that the linagliptin contained in the linagliptin hydrate-containing preparation maintains a hydrated form when the equilibrium relative humidity is 10% or more and 45% or less.

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