TW201801725A - Solid formulation for oral administration containing amorphous solifenacin and a process for the preparation thereof - Google Patents

Abstract

Provided are a solid formulation for oral administration containing amorphous solifenacin, a pharmaceutically acceptable salt thereof, hypromellose, and a low-substituted hydroxypropyl cellulose, and a method of preparing the solid formulation.

Description

Oral solid preparation containing amorphous solifenacin and preparation method thereof

The invention relates to an oral solid preparation containing amorphous solifenacin (solifenacin) and a preparation method thereof. More specifically, the present invention relates to an amorphous solifenacin which has a significantly reduced tendency to crystallize and a dissolution rate. Excellent oral solid preparation containing amorphous sofenafil and preparation method thereof.

As a quinoline derivative, solifenacin has the structure of the following Chemical Formula 1, and its chemical name is (1R, 3'R) -3'-quinuclidinyl-1-phenyl-1,2,3,4 -Tetrahydro-2-isoquinoline carboxylic acid ester. [Chemical Formula 1]

It has been reported that the above-mentioned solifenacin or its pharmaceutically acceptable salts have excellent selective antagonistic effects on muscarinic M ₃ receptors, as neurogenic urinary frequency, neurogenic bladder, enuresis, unstable bladder, bladder It is useful as a prophylactic and therapeutic agent for urinary diseases such as contracture or chronic cystitis, or respiratory diseases such as chronic obstructive pulmonary disease, chronic bronchitis, asthma or rhinitis (Patent Document 1: EP0801067).

The crystalline form of solifenacin succinate has the following problems: When the wet granulation process is performed, the crystalline form becomes amorphous, and the stability of the active ingredient decreases as the soft substance increases with time.

On the other hand, amorphous solifenacin has the advantage that its solubility is higher than that of crystalline sofenacin, which is advantageous in terms of pharmacokinetics. The above-mentioned amorphous solifenacin has a problem that it changes into a crystalline form sofonacin over time, and therefore the crystal form of the main component changes depending on storage conditions. However, the method for stabilizing the above-mentioned crystalline sofosinate cannot effectively improve the stability of the amorphous sofinaxin.

[Problems to be Solved by the Invention]

There is a need to develop an amorphous sofosinate oral formulation that can inhibit the crystallization of amorphous sofinafil even after elapse of time and does not hinder dissolution.

One embodiment of the present invention provides an amorphous solifenacin-containing oral solid preparation which is excellent in stability of an active ingredient and does not delay dissolution.

Another embodiment of the present invention provides a method for preparing an oral solid preparation containing amorphous solifenacin that has excellent stability of active ingredients and does not delay dissolution.

[Means for solving problems]

An embodiment of the present invention provides an oral solid preparation including amorphous solifenacin or a pharmaceutically acceptable salt thereof, hypromellose, and low-substituted hydroxypropylcellulose.

Another embodiment of the present invention provides a method for preparing the above-mentioned oral solid preparation according to an embodiment of the present invention, which includes the following steps: for a drug comprising solifenacin or a pharmaceutically acceptable salt thereof and hypromellose A step of spray-drying the mixed solution to prepare an amorphous solifenacin powder; and a step of solidly formulating the above-mentioned amorphous sofenacin powder together with a low-substituted hydroxypropyl cellulose and a pharmaceutically acceptable additive .

[Effect of the invention]

Amorphous sofenacin-containing oral solid preparation according to an embodiment of the present invention contains hypromellose and low-substituted hydroxypropyl cellulose, thereby stably maintaining the amorphous even over time without delaying the active ingredient Dissolution, so the above solid preparation can achieve effective oral administration of amorphous sofenacin.

Hereinafter, the present invention will be described in more detail.

Unless defined differently, all technical terms used in the present invention are used with the same meanings as commonly understood by an ordinary person in the related field of the present invention. In addition, although a preferable method or sample is described in this specification, those similar or the same are also included in the scope of the present invention. Moreover, even if the numerical value described in this specification is not indicated, it is considered to include the meaning of "about." The entire contents of all publications described as references in this specification are incorporated herein by reference.

In one embodiment, the present invention provides an oral solid preparation comprising amorphous solifenacin or a pharmaceutically acceptable salt thereof, hypromellose, and low-substituted hydroxypropylcellulose.

In another embodiment, the present invention provides an oral solid preparation, which includes amorphous solifenacin or a pharmaceutically acceptable salt thereof, hypromellose, and low-substituted hydroxypropylcellulose. The total weight of naxin or a pharmaceutically acceptable salt thereof, and more than 90% by weight of the aforementioned amorphous solifenacin or a pharmaceutically acceptable salt thereof is amorphous.

The above-mentioned pharmaceutically acceptable salts of Sofinafil include acid addition salts or quaternary ammonium salts, and the acid addition salts include inorganic acid salts or organic acid salts.

The inorganic acid salt includes, but is not limited to, hydrochloride, hydrobromide, hydroiodate, sulfate, nitrate, or phosphate. The organic acid salts include formate, acetate, propionate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, Citrate, tartrate, carbonate, picrate, mesylate, ethanesulfonate, glutamate, and the like are not limited thereto.

In a specific example, the pharmaceutically acceptable salt of Sofinaxin is Sofinacin Succinate.

The present inventors made intensive research in order to develop a solid preparation with high stability which can inhibit the amorphous morphinoxacin from changing into a crystalline form. As a result, it was found that the preparation of a solid preparation containing hypromellose can be more effective than using In the case of polymers other than the above-mentioned hypromellose, the amorphous crystallization was significantly blocked. Specifically, it was confirmed that when spray-dried powder was prepared together with various polymer compounds of sofenacin succinate, and solid formulation was carried out, hypromellose was included as the polymer compound. At this time, the amorphous sofenacin succinate remains amorphous even under severe storage conditions for a long period of time. On the contrary, when it contains other polymers, it becomes crystalline (see Test Example 1).

In a specific example, the hypromellose may be hypromellose having 16.5% to 30% of methoxyl and 4% to 32% of hydroxypropoxyl, but it is not limited to this. . In a specific example, the hypromellose may be hypromellose 1828, hypromellose 2208, hypromellose 2906, or hypromellose 2910.

The aforementioned hypromellose fiber may be present in an amount of 0.1 to 5.0 parts by weight, more specifically 0.5 to 3.0 parts by weight, with respect to 1 part by weight of the above-mentioned amorphous solifenacin or a pharmaceutically acceptable salt thereof. Vegetarian. When the above content is not reached, the crystallization blocking effect of inhibiting the crystallization of amorphous sofenafil will not be sufficiently exhibited. When it exceeds the above content, the viscosity will be high and the process will be set. cause problems.

In addition, the present inventors have found a problem and have studied a method for improving the problem by preparing a solid preparation containing amorphous solifenacin or a pharmaceutically acceptable salt thereof containing hypromellose In this case, stability can be improved by inhibiting amorphous sofenafil from changing to a crystalline form, and conversely, the dissolution rate of the active ingredient is delayed. As a result, it was found that the dissolution rate in the case of preparing a solid preparation containing low-substituted hydroxypropylcellulose in combination with the above-mentioned hypromellose as compared with the case where low-substituted hydroxypropylcellulose was not contained was remarkable. Improved, showing a dissolution rate similar to the control formulation. Specifically, it was confirmed that, compared with the case where low-substituted hydroxypropyl cellulose was not contained, a low-substitution was added after the spray-dried powder was prepared by combining sofenacin succinate together with hypromellose. In the case of hydroxypropylcellulose and solid preparation, the dissolution rate was significantly improved, and the dissolution rate was similar to that of the control preparation, thereby solving the problem of delayed dissolution of the active ingredient caused by the use of hypromellose ( Refer to Test Example 2).

The above-mentioned low-substituted hydroxypropyl cellulose may be present in an amount of 2% to 10% relative to the total weight of the above-mentioned oral solid preparation, and more specifically, the above-mentioned low-substituted hydroxypropyl cellulose may be present in an amount of 2% to 6% Cellulose. When the content is not reached, the effect of improving the dissolution of the active ingredient may not be sufficiently exhibited. When the content exceeds the content, there may be a decrease in hardness, an increase in friability, and a tablet during coating. Tendency to pharmaceutical problems such as poor drug properties (see Test Example 3).

The above-mentioned oral solid preparations can be formulated into pills, capsules, tablets, powders, granules, or dry syrups, but are not limited thereto. More specifically, the oral solid preparation may be in the form of a capsule or a tablet. When the solid preparation of the present invention is a capsule, the capsule may be in a form including powder, granules, tablets, dry syrup, pills, and the like inside.

In a specific example, the oral solid preparation is a tablet.

In a specific example, after preparing a mixed solution of the above-mentioned sofenacin or a pharmaceutically acceptable salt thereof and the above-mentioned hypromellose into a spray-dried powder form, the above-mentioned low-substituted hydroxypropyl cellulose may be used The mixed powder prepared by adding together with pharmaceutically acceptable additives optionally is included in the aforementioned oral solid preparation. The meaning of the above "may be included as a mixed powder in the above-mentioned oral solid preparations" is interpreted to include the following cases: directly including the mixture, filling the capsules to include the above mixture, directly injecting the mixture, and using the mixed powder to prepare a granular form including The above-mentioned mixture includes the above-mentioned mixture in a state in which the properties of the mixed powder are not maintained due to another processing process such as tableting the granules of the above-mentioned mixture into tablets.

The solvent used to prepare the above mixed solution may be amorphous sofrinacin or a pharmaceutically acceptable salt thereof and hypromellose, and any pharmaceutically acceptable solvent such as ethanol and water Mixed solvents. In a specific example, the mixed solvent is a mixed solution of ethanol and purified water, and more specifically, in a mixed solution of ethanol and purified water, the volume ratio of ethanol: water may be 1 to 9: 9 to 1, for example The volume ratio of ethanol: water may be about 5: 5, but is not limited thereto.

In a specific example, the solid preparation is a tablet, which may be a tablet made by a direct compression method of directly tableting the raw material mixture, or may be a tablet prepared by pelleting the raw material mixture. Tablets made by the granule compression method. In a specific example, the tablet may be a tablet made by a direct compression method.

The pharmaceutically acceptable additives included in the above-mentioned oral solid preparations of the present invention may be any additives normally included in oral solid preparations, such as optional free diluents, binding agents, disintegrants, lubricants, antioxidants, and the like And any combination of groups.

The above diluents are used for bulking, and can be selected from lactose or hydrates thereof, microcrystalline cellulose, mannitol, starch, sucrose, lactose, sorbitol, xylitol, glucose, calcium dihydrogen phosphate and the like. The group formed by the combination is not limited to this.

The above-mentioned binding agent may be selected from the group consisting of polyvinylpyrrolidone, copovidone, polyethylene glycol, light anhydrous silicic acid, and any combination thereof, but is not limited thereto.

The above disintegrants can be selected from freely cross-linked polyvinyl pyrrolidone, croscarmellose sodium, sodium starch gluconate, starch, alginic acid or its sodium salt, sodium carboxymethyl cellulose, microcrystalline cellulose, The group consisting of any combination of powdered cellulose, pregelatinized starch, and the like is not limited thereto.

The above lubricants can be selected from stearic acid, stearic acid metal salts (such as calcium stearate, magnesium stearate, etc.), talc, silicic acid gum, sucrose fatty acid esters, hydrogenated vegetable oils, waxes, glycerin fatty acids The group consisting of any combination of esters, glyceryl dibehenate, and the like is not limited thereto.

The above-mentioned antioxidant refers to any pharmaceutically acceptable additive effective in suppressing the oxidation of the active ingredient, and may be a neutral antioxidant. The neutral antioxidant may be an antioxidant including a phenol derivative, and more specifically, may be any one selected from the group consisting of butylhydroxytoluene, butylhydroxymethoxybenzene, propyl gallate, vitamin E, and the like. combination. In a specific example, the neutral antioxidant may be selected from butylhydroxytoluene, butylhydroxymethoxybenzene, propyl gallate, and any combination thereof.

In a specific example, each of the above-mentioned oral solid preparations may contain about 2.5 mg to 10 mg of sofenacin as an active ingredient or a pharmaceutically acceptable salt thereof as a free base, and more specifically, may Contains about 5 mg to 10 mg.

The above-mentioned oral solid preparations can be administered to mammals including humans having any indication of solifenacin or a pharmaceutically acceptable salt thereof. Therefore, the above-mentioned oral solid preparation can be used to treat or prevent any disease effective in terms of excellent selective antagonistic effect on muscarinic M ₃ receptors. The above diseases include urinary diseases such as frequent urinary frequency, neurogenic bladder, enuresis, allergic cystitis, bladder spasm (contracture) or chronic cystitis; respiratory organs such as chronic obstructive pulmonary disease, chronic bronchitis, asthma or rhinitis Disease is not limited to this. In a specific example, the aforementioned oral solid preparation can be used to treat allergic bladder disease.

In another embodiment of the present invention, there is provided a method for preparing the above-mentioned oral solid preparation according to an embodiment of the present invention, which comprises the following steps: The method includes the following steps: A step of spray-drying a mixed solution of cellulose to prepare amorphous sofenacin powder; and a solid preparation comprising the above-mentioned amorphous sofenacin powder together with low-substituted hydroxypropyl cellulose and pharmaceutically acceptable additives Steps.

The details of the method for producing an oral solid preparation of the present embodiment can be directly applied to the description of the above-mentioned oral solid preparation of one embodiment of the present invention.

In a specific example, any method known in the art can be prepared by solidifying the above-mentioned amorphous sofenacin powder together with low-substituted hydroxypropyl cellulose and pharmaceutically acceptable additives into a solid preparation. The solid preparation step can be performed by any known method of forming a pill, capsule, tablet, powder, granule, or dry syrup, for example.

In a specific example, the above solid preparation step may be the following method: after mixing the amorphous solifenacin powder together with the low-substituted hydroxypropyl cellulose and a pharmaceutically acceptable additive, the method is performed by tableting. Preparation of tablets. The above-mentioned tabletting may be an indirect tableting method in which tableting is performed after the pellets are prepared, or a direct tableting method in which tableting is performed after mixing with other pharmaceutically acceptable additives without performing the pellet preparation process. In a specific example, the above-mentioned ingot making is a direct ingot making method.

Hereinafter, the present invention will be described in detail based on the following examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

[Example]

Example 1 : Preparation of amorphous solifenacin succinate tablets According to the composition as shown in Table 1 below, first, solfenacin succinate, hypromellose and butylhydroxytoluene were dissolved in ethanol and A liquid obtained by purifying a mixture of water (ethanol: water = 5: 5) was spray-dried to obtain an amorphous solifenacin succinate spray-dried powder. After the above-mentioned amorphous solfenacin succinate spray-dried powder was dried at 60 ° C, sieving was performed using 30 mesh, and then all remaining ingredients were added to prepare a mixture. Thereafter, the above mixture was ingoted by a rotary punching machine (GRC-18, Sejong Machinery, Korea) using a circular punch having a diameter of 8.0 mm to prepare sofina having a hardness of about 5 kp to 12 kp. New succinate tablets. Thereafter, the liquid obtained by dispersing Opadry Pink in purified water was used as a coating liquid to coat the above-mentioned sofenacin succinate tablet.

[Table 1]

Examples 2 to 3 : Preparation of amorphous sofosinacin succinate tablets The hypromellose content of Examples 2 to 3 shown in Table 1 was used in place of the hypromellose of Example 1 above. The content of methylcellulose was performed in the same manner as in Example 1 described above to prepare a solfenacin succinate tablet.

Comparative Example 1 : Preparation of amorphous solifenacin succinate tablet According to the composition shown in Table 2 below, first, solfenacin succinate, lactose hydrate and butylhydroxytoluene were dissolved in ethanol and purified water. The liquid obtained by using a mixed solvent (ethanol: water = 5: 5) was spray-dried to obtain an amorphous sofosinacin succinate spray-dried powder. After the above-mentioned amorphous solfenacin succinate spray-dried powder was dried at 60 ° C, sieving was performed using 30 mesh, and then all remaining ingredients were added to prepare a mixture. Thereafter, the above mixture was ingoted by a rotary punching machine (GRC-18, Sejong Machinery, Korea) using a circular punch having a diameter of 8.0 mm to prepare sofina having a hardness of about 5 kp to 12 kp. New succinate tablets. Thereafter, the prepared sofoenacin succinate tablet was coated with a liquid obtained by dispersing Opadry pink into purified water as a coating liquid.

[Table 2]

Comparative Example 2 to Comparative Example 3 : Preparation of Amorphous Sofinafil Succinate Tablets D-mannitol or polyvinylpyrrolidone in the content of Comparative Example 2 to Comparative Example 3 shown in Table 2 above was used instead of the above comparison The above-mentioned lactose hydrate of Example 1 was prepared in the same manner as in Comparative Example 1 above to prepare a solfenacin succinate tablet.

Test Example 1 : Confirmation of crystal form under severe storage conditions The amorphous solifenacin succinate obtained in the above Examples 1 to 3 and Comparative Examples 1 to 3 was stored under the severe conditions described below. After spray-dried powder, the crystal form was analyzed by XRD.

<Severe storage conditions> Storage conditions: Packed in HDPE bottles at 60 ° C Test time: Initial, 2 weeks, and 4 weeks Analytical object: Amorphous sofenacin succinate

＜ XRD analysis conditions of solifenacin succinate ＞ Equipment: XRD (Bruker D8 ADVANCE, Germany)

The crystal form changes of the amorphous sofosinacin succinate measured under the above conditions are shown in Table 3 below. In addition, XRD results of Examples 1 to 3 after 4 weeks are shown in FIGS. 1, 2, and 3, and XRD results of Comparative Examples 1 to 3 after 2 weeks are shown in FIG. 4, Figure 5 and Figure 6.

[table 3]

According to the XRD analysis results in Table 3 and FIG. 1 to FIG. 6 described above, it was confirmed that when hypromellose was contained, the amorphous solifenacin succinate remained amorphous even under severe storage conditions for a long time. In contrast, when it contains other polymers, it becomes a crystalline form.

Example 4 to Example 7 : Preparation of amorphous solifenacin succinate tablets According to the composition shown in Table 4 below, firstly, the solfenacin succinate, hypromellose and butylhydroxytoluene A liquid obtained by dissolving a mixture of ethanol and purified water (ethanol: water = 86: 14) was spray-dried to obtain an amorphous sofosinacin succinate spray-dried powder. After the above-mentioned amorphous solfenacin succinate spray-dried powder was dried at 60 ° C, sieving was performed using 30 mesh, and then all remaining ingredients were added to prepare a mixture. Thereafter, the above mixture was ingoted by a rotary punching machine (GRC-18, Sejong Machinery, Korea) using a circular punch having a diameter of 7.5 mm to prepare sofina having a hardness of about 5 kp to 12 kp. New succinate tablets. Thereafter, the prepared sofoenacin succinate tablet was coated with a liquid obtained by dispersing Opadry pink into purified water as a coating liquid.

[Table 4]

Comparative Example 4 to Comparative Example 7 : Preparation of Amorphous Sofenacin Succinate Tablets According to the composition shown in Table 4 above, firstly, the solfanacin succinate, hypromellose and butylhydroxytoluene A liquid obtained by dissolving a mixture of ethanol and purified water (ethanol: water = 86: 14) was spray-dried to obtain an amorphous sofosinacin succinate spray-dried powder. After the above-mentioned amorphous solfenacin succinate spray-dried powder was dried at 60 ° C, sieving was performed using 30 mesh, and then all remaining ingredients were added to prepare a mixture. Thereafter, the above mixture was ingoted by a rotary punching machine (GRC-18, Sejong Machinery, Korea) using a circular punch having a diameter of 7.5 mm to prepare sofina having a hardness of about 5 kp to 12 kp. New succinate tablets. Thereafter, the prepared sofoenacin succinate tablet was coated with a liquid obtained by dispersing Opadry pink into purified water as a coating liquid.

Test Example 2 : Dissolution evaluation corresponding to the composition of the formulation The following conditions were used to evaluate the dissolution, together with the amorphous solifenacin succinate tablets obtained in the above Examples 4 to 7 and Comparative Examples 4 to 7 The agent was used to compare and evaluate the dissolution rate of 10 mg of Weixi Kang film-coated tablet (Vesicare Tab. 10 mg, manufactured by Aatella Pharmaceutical Co., Ltd.) as a control preparation.

<Sofinavir's new dissolution method and analysis conditions> Dissolution method: Korean Pharmacopoeia 10 revision, method 2 (stirring paddle 50 rpm) Dissolution medium: purified water Specimen: 6 tablets Equipment used: HPLC ( High Performance Liquid Chromatography (HPLC) (Hitachi 5000 series, Japan) Detector: UV spectrophotometer (measurement wavelength: 210 nm) Column: stainless steel tube with an inner diameter of about 4.6 mm and a length of about 15 cm is filled with pellets 5 μm diameter silica gel column (Develosil ODS Column) mobile phase-potassium phosphate buffer (pH 6.0): acetonitrile = 65:35 phosphate buffer (pH 6.0): at After dissolving 8.7 g of anhydrous dipotassium hydrogen phosphate in 1 L of water, phosphoric acid was added to adjust the pH to 6.0. Flow rate: 1.5 mL / min Column temperature: 40 ° C

The dissolution rate of each preparation measured under the above analysis conditions is shown in Table 5 and FIG. 7 below.

[table 5]

As shown in the dissolution rate results in Table 5 above, it was confirmed that the initial dissolution rates of Examples 4, 6, and 7 using 3% or more of low-substituted hydroxypropylcellulose were improved and showed a difference from the control formulation. Similar dissolution results. In contrast, Example 5 using less than 2% of low-substituted hydroxypropyl cellulose and Comparative Examples 4 to 7 which did not use low-substituted hydroxypropyl cellulose at all were confirmed in 15 minutes and 30 minutes. At the time point, the dissolution rate was significantly lower than that of the control preparation, and Comparative Example 5 in which the cross-linked polyvinylpyrrolidone was used as a powerful disintegrant with a 5.0% increase was also difficult to expect a dissolution improvement effect.

Test Example 3 : Evaluation of friability corresponding to the composition of the preparation The friability of the amorphous solifenacin succinate tablets obtained in the above-mentioned Examples 4 to 7 and Comparative Examples 4 to 7 to evaluate.

[TABLE 6]

As shown in the friability measurement results in Table 6 above, it can be confirmed that in Examples 4 to 6, where 10% by weight or less of the low-substituted hydroxypropyl cellulose was used, the comparison was made without using the low-substituted hydroxypropyl cellulose at all. The chipping properties and friability of Examples 4 to Comparative Example 7 met the benchmark.

However, it was confirmed that Example 7 in which more than 10% of the low-substituted hydroxypropyl cellulose was added had higher friability at the same hardness. In addition, when the tabletting pressure is increased in Example 7, the tablet can no longer withstand the tabletting pressure and it is difficult to set a hardness of 7 KP or more.

So far, the present invention has been described focusing on the preferred embodiments of the present invention. Those having ordinary knowledge in the technical field to which the present invention pertains will appreciate that the present invention can be implemented in a form deformed within a range not departing from the essential characteristics of the present invention. Therefore, the embodiments disclosed above should be considered from an illustrative point of view, rather than from a limiting point of view. The scope of the present invention is expressed by the scope of patent application, not by the above description, and it should be construed that all differences within the scope equivalent to the scope of patent application are included in the present invention.

no

Figures 1 to 3 show the harsh storage conditions of the sofinacin oral solid preparations of Examples 1 to 3 of the present invention in a high-density polyethylene (HDPE) bottle packaging state at 60 ° C. X-ray diffraction (XRD) graph after 4 weeks. FIG. 4 to FIG. 6 are XRD graphs of the sofanacin oral solid preparations of Comparative Examples 1 to 3 after being stored under severe storage conditions in HDPE bottles at 60 ° C. for 2 weeks. FIG. 7 is a graph showing the results of a dissolution test performed on the sofinacin oral solid preparations of Examples 4 to 7 and Comparative Examples 4 to 7 according to the stirring paddle method of the second method of the Korean Pharmacopoeia.

Claims (12)

An oral solid preparation comprising amorphous solifenacin or a pharmaceutically acceptable salt thereof, hypromellose and low-substituted hydroxypropylcellulose. The oral solid preparation according to item 1 of the scope of application for a patent, wherein about 0.1 parts by weight to 5.0 parts by weight relative to 1 part by weight of said amorphous sofenacin or a pharmaceutically acceptable salt thereof Hypromellose. The oral solid preparation according to item 2 of the scope of patent application, wherein the amorphous solifenacin or a pharmaceutically acceptable salt thereof is included in an amount of about 0.5 parts by weight to 3.0 parts by weight, relative to 1 part by weight of the amorphous solifenacin or a pharmaceutically acceptable salt thereof. Hypromellose. The oral solid preparation according to item 1 of the scope of patent application, wherein the low-substituted hydroxypropyl cellulose is included in an amount of about 2% to 10% with respect to the total weight of the oral solid preparation. The oral solid preparation according to item 4 of the scope of patent application, wherein the low-substituted hydroxypropyl cellulose is included in an amount of about 2% to 6% with respect to the total weight of the oral solid preparation. The oral solid preparation according to item 1 of the scope of the patent application, wherein the amorphous solifenacin or a pharmaceutically acceptable salt thereof is amorphous solifenacin succinate. The oral solid preparation according to item 1 of the scope of application, wherein the oral solid preparation is selected from the group consisting of pills, powders, granules, dry syrups, tablets and capsules. The oral solid preparation according to item 1 of the scope of the patent application, wherein each unit dosage form contains the amorphous sofenacin or a pharmaceutically acceptable salt thereof as a free base in an amount of about 2.5 mg to 10 mg. The oral solid preparation according to item 1 of the scope of application for a patent is an oral solid preparation for the treatment of allergic bladder disease. A method for preparing an oral solid preparation, the preparation of the oral solid preparation according to any one of claims 1 to 9 of the scope of application for patents, comprising: comprising sofinacin or a pharmaceutically acceptable salt thereof and A step of spray-drying a mixed solution of hypromellose to prepare an amorphous solifenacin powder; and the amorphous sofenacin powder together with low-substituted hydroxypropyl cellulose and a pharmaceutically acceptable additive The solid preparation step is performed together. The method for preparing an oral solid preparation according to item 10 of the application, wherein the solid preparation step is performed after mixing the amorphous solifenacin powder with the pharmaceutically acceptable additive. Tablets are prepared by tabletting. The method for preparing an oral solid preparation according to item 11 of the application, wherein the tabletting method is a direct tableting method.