JP2020121776A - Desiccant package of esomeprazole preparation - Google Patents

Abstract

To provide means for stably storing Esomeprazole or a pharmaceutically acceptable salt thereof, especially means for storing Esomeprazole or a pharmaceutically acceptable salt thereof under accelerated conditions (under a high temperature).SOLUTION: In the present invention, a package storing a preparation containing Esomeprazole or a pharmaceutically acceptable salt thereof is provided. In one embodiment, the package may be an aluminum pillow. In one embodiment, the package further contains a desiccant. In one embodiment, the package is the aluminum pillow and further contains the desiccant.SELECTED DRAWING: None

Description

The present invention relates to the field of pharmaceutical formulations.

Esomeprazole (generic name) is an optical isomer (S form) contained in omeprazole which is a racemate, and is a drug having a gastric acid secretion inhibitory action as a pharmacological action. Esomeprazole is a gastric ulcer, duodenal ulcer, anastomotic ulcer, Zollinger-Ellison syndrome, reflux esophagitis, non-erosive gastroesophageal reflux disease, suppression of recurrence of gastric ulcer or duodenal ulcer when nonsteroidal anti-inflammatory drug is administered, low It is useful for treatment such as suppression of recurrence of gastric ulcer and duodenal ulcer when a dose of aspirin is administered (Non-Patent Document 1).

Esomeprazole is not very stable, and in the storage form in which capsules were packed in PTP, under the accelerated test conditions (40° C./75% RH), a storage period of 3 months resulted in an increase in related substances, a decrease in dissolution and It is known that a decrease in content is recognized (Non-Patent Document 1).

"Nexium (registered trademark) capsule 10 mg 20 mg" Pharmaceutical interview form Revised February 2016 (revised 10th edition)

In the present invention, a package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof is provided. In such a package, the stability of the contained esomeprazole or its pharmaceutically acceptable salt is significantly improved. In one embodiment, the package may be an aluminum pillow. In one embodiment, the package further contains a desiccant. In one preferred embodiment, the package is an aluminum pillow and further contains a desiccant.

For example, in the present disclosure, the following items are provided.
(Item 1) A package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof, wherein the package is an aluminum pillow.
(Item 2) A package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof, wherein the package further contains a desiccant.
(Item 3) A package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof, wherein the package is an aluminum pillow, and the package further contains a desiccant. body.
(Item 4) The package according to any of the preceding items, wherein the desiccant contains calcium chloride, silica gel, calcium oxide or zeolite.
(Item 5) The package according to any of the preceding items, wherein the desiccant contains calcium chloride.
(Item 6) The package according to any of the preceding items, wherein the preparation contains esomeprazole magnesium hydrate.
(Item 7) The package according to any one of the above items, wherein the package contains a PTP package containing the formulation.
(Item 8) The package according to any one of the items, wherein the PTP package contains polypropylene.
(Item 9) The package according to any of the preceding items, wherein the formulation is a capsule encapsulating granules containing the esomeprazole or a pharmaceutically acceptable salt thereof.
(Item 10) The package according to any of the preceding items, wherein the core particles in the granules include crystalline cellulose.
(Item 11) The package according to any one of the preceding items, wherein the granules include a drug substance layer containing the esomeprazole or a pharmaceutically acceptable salt thereof on the core particles.
(Item 12) The package according to any one of the preceding items, wherein the granule contains 200 parts by weight or more of a drug substance layer with respect to 100 parts by weight of core particles.
(Item 13) The package according to any of the preceding items, wherein the granules include a barrier layer on the drug substance layer and an enteric layer on the barrier layer.
(Item 14) The package according to any of the preceding items, wherein the barrier layer contains hypromellose.

According to the present invention, it is possible to store esomeprazole or a pharmaceutically acceptable salt thereof while suppressing changes in physicochemical properties. In particular, it is possible to store esomeprazole or a pharmaceutically acceptable salt thereof under accelerated conditions (under high temperature).

The present invention will be described below with reference to the best mode. It should be understood that throughout this specification, the singular expression also includes the concept of the plural unless specifically stated otherwise. Therefore, it should be understood that a singular article (eg, "a", "an", "the" in English, etc.) also includes its plural concept unless otherwise specified. .. Further, it should be understood that the terms used in the present specification have meanings commonly used in the art, unless otherwise specified. Accordingly, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.

<Definition>
The definitions of terms and/or basic technical contents used particularly in the present specification will be described below as appropriate.

As used herein, "pharmaceutically acceptable" means approved by a governmental regulatory agency for use in animals, and more particularly humans, or in a pharmacopoeia or other generally accepted pharmacopoeia. Means listed in.

As used herein, the term “packaging body” refers to any material capable of containing a substance (eg, pharmaceutical product) therein.

In the present specification, "closed container", "airtight container" and "sealed container" refer to those defined by the Japanese Pharmacopoeia. More specifically, the "closed container" refers to a container that can prevent solid foreign matter from being mixed in and can prevent loss of contents under normal handling, transportation, or storage conditions. The "airtight container" means a container which does not allow solid or liquid foreign matter to enter under normal handling, transportation, or storage conditions, and which can prevent loss, deliquescence, deliquescence or evaporation of the drug in the contents. The hermetically sealed container refers to a container in which gas does not enter during normal handling, transportation or storage.

In the present specification, the “moisture absorption rate” refers to the moisture absorption capacity of the desiccant at a certain relative humidity, which is calculated according to the method specified in JIS standard.

More specifically, the moisture absorption rate is calculated by the following method. The sample was crushed in advance, sieved using a nominal size of 840 or less according to JIS Z 8801 (standard sieve), mixed well, and heated at 170 to 190° C. for about 2 hours, and then type A (moisture at low humidity was used). 0.3 to 0.5 g for a desiccant having a strong adsorption force, or 0.2 to 0.4 g for a B type (a desiccant that absorbs a large amount of moisture at high humidity and has a large adsorption capacity). Quickly open the bottom of a flat balance bottle (having an outer diameter of 40 mm, a height of 20 mm, and a ground glass stopper according to JIS R 3503 (glass instrument for chemical analysis) with a ground glass stopper) to a uniform thickness as much as possible, and immediately close the lid. And cool to room temperature in a desiccator. Next, this is weighed and placed in a glass closed vessel (desiccator according to JIS R 3503, the amount of sulfuric acid aqueous solution is 100 ml or more per sample) containing a sulfuric acid aqueous solution having a concentration adjusted to the target relative humidity. While keeping the relative humidity of 20%, 50% or 90%, the temperature is kept at 25±2.5° C. for 48 hours, then, this is taken out, and the lid is immediately closed and weighed. The moisture absorption rate is calculated as (W ₁ −W ₀ )/W ₀ ×100, where W ₀ is the dry mass (g) of the sample, and W ₁ is the mass (g) of the sample that has absorbed moisture.

In the present specification, “about” means that a variation of ±10% of the indicated value is allowed. In the present specification, when explicitly stated as “within a range” of “two values”, the range also includes the two values themselves.

<Drug substance>
The preparation of the present invention contains esomeprazole or a pharmaceutically acceptable salt thereof as a drug substance. Also, the drug substance may be a hydrate of esomeprazole or a pharmaceutically acceptable salt thereof. In one embodiment, the formulation of the invention comprises a salt of esomeprazole as a drug substance, preferably a metal salt of esomeprazole (desirably an alkaline earth metal salt), more preferably of esomeprazole. Magnesium salt, most preferably esomeprazole magnesium hydrate. The examples herein demonstrate a marked improvement in stability when using an esomeprazole formulation (including esomeprazole magnesium hydrate as the drug substance).

The median diameter (d50) of esomeprazole or a salt thereof is preferably about 0.1 to about 50.0 μm, more preferably about 1.0 to about 20.0 μm. The salt of esomeprazole can be adjusted to an arbitrary particle size by performing dry or wet pulverization as needed. The salt of esomeprazole is contained in the drug substance layer portion in the granule, and is about 5.0% by weight or more, about 6.0 to about 50.0% by weight, preferably about 8.% by weight based on the total weight of the granule. It is contained in the granule in the range of 0 to about 35.0% by weight. The drug substance layer can be formed by spraying and drying a liquid in which the drug substance is dispersed/suspended in core particles.

<Package>
The package defines an internal space, and medicines can be stored in the internal space. Preferably, the package contains a desiccant together with the medicine in the internal space. As the package, one having a shape and a material known in the art can be used. Examples of the package include an airtight container, an airtight container or an airtight container. The package can be a pillow package, an SP package, a PTP package, a stick package, a glass bottle package, a plastic bottle package or a separate package, and these can be used in combination as necessary.

In one embodiment of the present invention, an aluminum pillow is used as the package. An aluminum pillow is a pillow package having an aluminum foil layer in the layer structure. Pillow packaging is a type of bag-like packaging, and includes, for example, packaging in which the vertical center portions of packaging materials are stuck together and the upper and lower edges are sealed. When it is difficult to ensure quality with only the primary packaging, a secondary packaging is often made of a composite film laminated with aluminum foil for protection from moisture and light. When the pillow wrapping is adopted, it is possible to further store another wrapping body for holding the medicine in the pillow wrapping body.

In a further embodiment of the invention, the package contains a PTP package containing the formulation. PTP (Press Through Pack) packaging includes a sheet-shaped packaging in which a solid preparation such as a tablet or a capsule is sandwiched between plastic and aluminum. By pressing the plastic part hard, the aluminum is broken and the formulation inside is taken out one by one.

<Drying agent>
The package of the present invention preferably contains a desiccant. As the desiccant, those known in the art can be used. For example, as the chemical desiccant, calcium chloride, quick lime, phosphorus pentoxide, concentrated sulfuric acid, sodium hydroxide or potassium hydroxide, metallic sodium can be used. , Anhydrous sodium sulfate, anhydrous copper sulfate, magnesium perchlorate, and physical desiccants (which adsorb water molecules on the porous surface) include silica gel, aluminum oxide, molecular sieves, allophane, and zeolite. To be The moisture absorption of the desiccant may be 20.0% or more at 90% relative humidity, preferably the moisture absorption of the desiccant may be 30.0% or more at 90% relative humidity.

Examples of the desiccant include those containing calcium chloride, silica gel, calcium oxide or zeolite. The desiccant preferably comprises calcium chloride. In the examples herein, it has been demonstrated that inclusion of a desiccant containing calcium chloride in a package with the formulation could improve the chemical stability of the salt of esomeprazole. .. The desiccant containing calcium chloride may be in the form of a sheet, for example. As an example, it is possible to use a commercially available ID sheet.

The amount of the desiccant contained in the package can be adjusted according to the shape of the package, and for example, contains about 1 mg to about 100 g, about 50 mg to about 50 g, or about 100 mg to about 10 g of the desiccant. can do. In one embodiment, the package contains about 1 g of desiccant.

The amount of desiccant in the package may be a relatively constant proportion of the total amount of esomeprazole or its pharmaceutically acceptable salt in the formulation contained in the package. For example, the desiccant in the package is about 50 parts by weight or more, about 60 parts by weight or more, relative to 100 parts by weight of esomeprazole or a pharmaceutically acceptable salt thereof in the formulation contained in the package. About 70 parts by weight or more, about 80 parts by weight or more, about 90 parts by weight or more, about 100 parts by weight or more, about 110 parts by weight or more, about 120 parts by weight or more, about 130 parts by weight or more, about 140 parts by weight or more, about 150 It can be greater than or equal to parts by weight.

<Formulation>
In the present invention, esomeprazole or a pharmaceutically acceptable salt thereof is preferably used after being formulated into a suitable formulation. Examples of formulations include granules, tablets, powders, capsules and the like.

The granules may preferably include core particles having a drug substance layer formed thereon. Core particles can be formed from an excipient such as, for example, crystalline cellulose. Excipients known in the art, including those described herein, can be used, but are preferably crystalline cellulose. The core particles may optionally include further additives.

The drug substance layer may be a layer containing the drug substance and a binder after drying. Any binder known in the art can be used, including those described herein, but is preferably methylcellulose. The drug substance layer may optionally include further additives. In the granule, the drug substance layer may be about 180 parts by weight or more, preferably about 200 parts by weight or more, based on 100 parts by weight of the core particles.

The granules in the present invention may include a barrier layer on the drug substance layer. The barrier layer blocks contact between the drug substance layer and the enteric layer formed on the drug substance layer as necessary. The barrier layer may include, for example, a component known as a coating agent. As the coating agent, those known in the art, including those described herein, can be used, but hypromellose and/or talc are preferable. The barrier layer preferably comprises hypromellose. The barrier layer may optionally include further additives.

The granules in the present invention may include an enteric layer. Specific examples of the enteric polymer include methacrylic acid copolymers (methacrylic acid copolymer L, methacrylic acid copolymer LD (solid content), methacrylic acid copolymer S, etc.), hypromellose phthalate ester, hypromellose acetate succinate, carboxy. Methyl ethyl cellulose and the like can be mentioned, but methacrylic acid copolymer is preferable, and methacrylic acid copolymer LD (solid content) or methacrylic acid copolymer L is more preferable. The enteric polymer does not substantially dissolve in an aqueous solution solvent having an acidic pH value assuming the gastric environment, and does not dissolve in an aqueous solution solvent having a neutral to alkaline pH value assuming the intestinal environment. It is characterized in that it dissolves satisfactorily, and as a specific example, it is preferably one that does not substantially dissolve in an aqueous solution having a pH of less than 5.0 and satisfactorily dissolves in an aqueous solution having a pH of 5.0 or more. The average molecular weight of the enteric polymer is 10,000 g/mol or more, preferably 100,000 g/mol or more, more preferably 200,000 to 1,000,000 g/mol. The enteric polymer is 1.0 part by weight or more, preferably 2.0 to 20.0 parts by weight, more preferably 3.0 to 10.0 parts by weight based on 100.0 parts by weight of the preparation of the present invention. A range may be included in the formulation. The enteric layer may optionally include further additives.

The formulation of the present invention may preferably have a multi-layer structure including a drug substance layer on core particles in a granule, a barrier layer on the drug substance layer, and an enteric layer on the barrier layer.

The formulation of the present invention is preferably a capsule packed with the above-mentioned granules. A capsule is a dosage form in which a drug is packed in a cylindrical container. The size of the capsule is represented by "No." and the volume decreases as the number increases. The largest capsule is No. 000 (1.37 ml) and the smallest capsule is No. 5 (0.13 ml). Capsules are used when filling powdered or granular medicines, and capsules are formed of components that dissolve in the body. Generally, the raw material for the capsule is often gelatin. Since capsules made of gelatin are colorless and transparent, titanium oxide may be added to make it opaque or a coloring agent may be added to add color to improve visibility. Capsules are generally vulnerable to moisture. On the other hand, the advantages include that a drug sensitive to heat can be formulated, and the release of the active ingredient is faster than that of tablets.

In order to produce the preparation of the present invention, in addition to the above-mentioned additives, commonly used excipients, binders, disintegrants, lubricants, plasticizers, flavoring agents, coating agents, etc. Additives can be used. In this specification, the interpretation of the terms of various additives (binders, plasticizers, coating agents, etc.) is assumed to fulfill the role of each additive in formulation. It is preferable that it is understood that the above-mentioned substances, which eventually fulfilled their role as additives.

Specific examples of excipients include lactose, crystalline cellulose, D-mannitol, erythritol, xylitol, sorbitol, isomalt, maltitol, sucrose, sucrose, glucose, corn starch, potato starch, rice starch, wheat starch, hydroxypropyl. Starch, pregelatinized starch, partially pregelatinized starch, sodium carboxymethyl starch, dextrin and the like can be mentioned, and preferably selected from D-mannitol and crystalline cellulose. Excipients may be contained in the formulation in the range of 10.0 to 60.0 parts by weight and 20.0 to 40.0 parts by weight based on 100.0 parts by weight of the formulation of the present invention.

Specific examples of the binder include hydroxypropyl cellulose, hydroxypropyl methyl cellulose (hypromellose), methyl cellulose, povidone, ethyl cellulose, polyvinyl alcohol, polyvinyl alcohol/acrylic acid/methyl methacrylate copolymer, polyethylene glycol, methacrylic acid copolymer, acrylic acid. Examples thereof include ethyl-methyl methacrylate copolymer, and hypromellose is preferable. The binder may be contained in the formulation in an amount of 0.1 to 20.0 parts by weight, preferably 2.0 to 6.0 parts by weight, based on 100.0 parts by weight of the formulation of the present invention.

Specific examples of the disintegrant include low-substituted hydroxypropyl cellulose, carmellose, carmellose calcium, carmellose sodium, hydroxypropyl starch, sodium carboxymethyl starch, crospovidone, agar powder and the like, preferably crospovidone. Is. The disintegrant may be contained in the formulation of the present invention preferably in the range of 1.0 to 20.0% by weight based on the total weight of the formulation.

Specific examples of the lubricant include light anhydrous silicic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, hardened oil, and the like, and magnesium stearate is preferable. The lubricant may be contained in the formulation of the present invention in the range of preferably 0.1 to 5.0% by weight based on the total weight of the formulation.

Specific examples of the plasticizer include tributyl citrate, triethyl citrate, glycerin, glycerin monostearate, sesame oil, castor oil, cottonseed oil/soybean oil mixture, dimethylpolysiloxane/silicon dioxide mixture, medium-chain fatty acid triglyceride, triacetin, phthalate. Examples thereof include diethyl acid, dioctyl phthalate, dibutyl phthalate, butylphthalylbutyl glycolate, propylene glycol, macrogol, polysorbate 80, stearic acid, and the like, preferably tributyl citrate, triethyl citrate, glycerin, glycerin mono. It is selected from stearate, macrogol, polysorbate 80 and stearic acid, and more preferably selected from triethyl citrate, glycerin monostearate and polysorbate 80. The plasticizer may be contained in the formulation according to the present invention in an amount of 0.1 to 10.0 parts by weight, preferably 0.2 to 2.0 parts by weight, based on 100.0 parts by weight of the formulation.

Specific examples of the corrigent include ascorbic acid, L-aspartic acid, aspartame, sucralose, acesulfame potassium, thaumatin and the like. The flavoring agent may be contained in the formulation of the present invention in the range of preferably 0.5 to 2.0% by weight based on the total weight of the formulation.

Specific examples of the coating agent include hydroxypropylmethyl cellulose (hypromellose), ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol/acrylic acid/methyl methacrylate copolymer, polyvinyl alcohol, polyethylene glycol, methacrylic acid copolymer, ethyl acrylate. -Methyl methacrylate copolymer dispersion, talc and the like can be mentioned, and preferably selected from hypromellose, talc, methacrylic acid copolymer, ethyl acrylate/methyl methacrylate copolymer dispersion. The coating agent is used in an amount of 10.0 parts by weight or more, preferably 15.0 parts by weight or more, more preferably 25.0 to 50.0 parts by weight based on 100.0 parts by weight of the formulation of the present invention. Can be contained in.

As a light-shielding agent, specifically, titanium oxide, yellow ferric oxide, ferric oxide, black iron oxide, yellow iron oxide, brown iron oxide, food yellow 4, food yellow 5, food yellow 4 aluminum lake, food Red No. 2, edible red No. 3, edible red No. 102, and the like can be mentioned, and preferably selected from titanium oxide, yellow ferric oxide, and ferric oxide, and more preferably titanium oxide. The light-shielding agent may be contained in the formulation of the present invention in an amount of 1.0% by weight or more, more preferably 10.0 to 30.0% by weight, based on the total weight of the formulation. The light-shielding agent is preferably contained in the coating layer of the preparation of the present invention, in which case 20.0 parts by weight of the light-shielding agent is added to 100.0 parts by weight of the coating layer (which is a single homogeneous layer). Above, preferably in the range of 30.0 parts by weight or more, can be contained in the coating layer.

Specific examples of the method for producing coated granules include a fluidized bed granulation method and a fine particle coating method, and the fine particle coating method is preferable. There is no difficulty in operating the above-mentioned production method, and the desired coated granules can be easily produced according to a conventional method. For example, in the fine particle coating method, a liquid containing a drug is sprayed and dried on an excipient in a fluidized bed granulator, and then a liquid containing a coating agent which is not an enteric polymer is sprayed and dried. The coated granules can be produced by spraying and drying a liquid containing a polymer and a non-enteric polymer. Capsules can be manufactured by filling capsules with coated granules (pellets).

In addition, a PTP sheet product containing the preparation of the present invention can be obtained by sandwiching and covering a capsule or tablet with a wrapping sheet and an aluminum foil and then heat-sealing. Specific materials used for the packaging sheet include polyvinyl chloride, polypropylene, polyvinylidene chloride, polychlorotrifluoroethylene and the like. In order to improve the stability of the tablet of the present invention against humidity, PTP sheet products are manufactured using a material having a drying function, PTP sheet products are packed in aluminum pillows, and a desiccant is put in a bottle. A known method such as encapsulation can be performed.

References such as scientific literatures, patents, and patent applications cited in this specification are hereby incorporated by reference to the same extent as if each were specifically described.

The present invention has been described above with reference to the preferred embodiments for easy understanding. Hereinafter, the present invention will be described based on examples, but the above description and the following examples are provided only for the purpose of illustration and not for the purpose of limiting the present invention. Accordingly, the scope of the invention is not limited to the embodiments or examples specifically described herein, but only by the claims.

<Production example>
A) Crystalline cellulose was put into a jet fluidized bed granulator (MP-01-SPC type/manufactured by Paulec), and esomeprazole magnesium salt hydrate was dispersed/suspended in a solution prepared by dissolving methyl cellulose in purified water. The resulting liquid was sprayed and dried to obtain a primary coated granule.

B) The primary coated granules obtained in A) above are put into a jet fluidized bed granulator, and a liquid in which talc is dispersed/suspended in a liquid in which hydroxypropylmethylcellulose is dissolved in purified water is sprayed/dried, A secondary coated granule was obtained.

C) The secondary coated granules obtained in B) above are put into a jet fluidized bed granulator, and glycerin monostearate glycerin monostearate, triethyl citrate and polysorbate 80 are dissolved in purified water to prepare a methacrylic acid copolymer LD ( Eudragit (registered trademark) L30D-55/manufactured by Evonik Japan) was added and gently mixed and stirred to obtain a coated pellet (third coated granule).

上記の顆粒をカプセルに封入し、カプセル剤を調製した。 The proportions of the ingredients of the granules are shown in Table 1 below.

The above granules were encapsulated to prepare capsules.

<Package>
(1) The capsules prepared in <Production Example> were enclosed in a PTP sheet made of polyvinyl chloride (PVC) to make a package (O-PVC).

(2) The capsules prepared in <Production Example> were enclosed in a PTP sheet made of polypropylene (PP) to make a package (O-PP).

(3) Encapsulate the capsule prepared in <Production Example> into a PTP sheet made of polypropylene (PP), and further house it in an aluminum pillow together with an ID sheet (calcium chloride-containing desiccant) to form a package. Yes (O-PP+Al+ID).

(4) The capsules prepared in <Production Example> were contained in a plastic (polyethylene) bottle (silica gel (about 1 g) provided on the back side of the cap) to form a package (O-poly SIL). ..

In addition, for comparison, a commercially available Nexium capsule 20 mg (Daiichi Sankyo Co., Ltd.) (N-PP) encapsulated in a PP-based PTP sheet and a Nexium capsule 20 mg 20 mg 500P ( Rose) bottle (Daiichi Sankyo Co., Ltd.) (N-polySIL) was used.

<Test example>
Each of the above-mentioned (1) to (4) and each commercial product package is stored under the condition of 40° C. and 75% relative humidity (accelerated condition) and before being stored for 1, 2, 3 and 6 months. The amount of total analog produced was measured. The measurement was performed by a high performance liquid chromatography method (a quantitative method used an area percentage method). The results of the above measurement results are summarized in Table 2 below.

<Results>
When packaged only with the PTP sheet, the amount of the analog increased significantly under accelerated conditions, resulting in non-compliance with the standard of 2.0% or less in 6 months. However, in the package containing the PTP sheet and the ID sheet (calcium chloride-containing desiccant) in the aluminum pillow, surprisingly, the amount of the analog was almost unchanged even after the storage for 6 months under the accelerated condition. It was From this, it can be understood that the stability of the esomeprazole preparation can be significantly improved by using an aluminum pillow and/or containing it together with a desiccant.

The amount of the analog formed at 6 months was different between N-PP and O-PP, and it is considered that the difference in the formulation partially contributes to the stability.

INDUSTRIAL APPLICABILITY The present invention can be used for providing a medicine containing esomeprazole or a salt thereof by stabilizing esomeprazole or a salt thereof.

Claims (14)

A package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof, wherein the package is an aluminum pillow. A package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof, wherein the package further contains a desiccant. A package containing a preparation containing esomeprazole or a pharmaceutically acceptable salt thereof, wherein the package is an aluminum pillow, and the package further contains a desiccant. The package according to any one of claims 1 to 3, wherein the desiccant contains calcium chloride, silica gel, calcium oxide or zeolite. The package according to claim 4, wherein the desiccant contains calcium chloride. The package according to any one of claims 1 to 5, wherein the formulation contains esomeprazole magnesium hydrate. The package according to any one of claims 1 to 6, wherein the package contains a PTP package containing the formulation. The package according to claim 7, wherein the PTP package includes polypropylene. The package according to any one of claims 1 to 8, wherein the formulation is a capsule containing granules containing the esomeprazole or a pharmaceutically acceptable salt thereof. The package according to claim 9, wherein the core particles in the granules include crystalline cellulose. The package according to claim 10, wherein the granules include a drug substance layer containing the esomeprazole or a pharmaceutically acceptable salt thereof on the core particles. The package according to claim 11, wherein the granules contain 200 parts by weight or more of a drug substance layer with respect to 100 parts by weight of core particles. The package according to claim 11 or 12, wherein the granules include a barrier layer on the drug substance layer and an enteric layer on the barrier layer. The package according to claim 13, wherein the barrier layer contains hypromellose.