JP2017214299A - Semisolid formulation and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a semisolid formulation that contains a poorly water-soluble medicine and has high heat stability.SOLUTION: A semisolid formulation contains (A) a poorly water-soluble medicine, (B) mannitol, (C) a gelator, and (D) water, with the mass of (D) component of 50 mass% or less relative to the total mass of the semisolid formulation. The mass ratio represented by (B) component/(A) component is preferably 0.001-0.15.SELECTED DRAWING: None

Description

  The present invention relates to a semi-solid preparation and a method for producing the same.

  Most oral preparations are tablets or powders, but may be difficult to take for reasons such as the dosage of the preparation and the size of the preparation. In particular, children and the elderly may have difficulty swallowing, and a dosage form that is easier to take is desired. Examples of dosage forms that can be easily taken include semi-solid preparations such as orally disintegrating tablets, gummi, and jelly.

  The method described in Patent Document 1 can be used as a method for containing a drug component of a pharmaceutical at a uniform concentration in a semi-solid preparation having a low water content, such as a gummy agent.

JP-A-10-130140

Many of the drug components of pharmaceuticals are poorly water-soluble, and the drug components are suspended and incorporated in the base material of the semi-solid preparation instead of being dissolved. However, semi-solid preparations with low water content may be sticky because the surface and the interior melt in a high-temperature environment (for example, 40 ° C or higher) due to suspension blending of poorly water-soluble drug components. Decline). This phenomenon is thought to be caused by the poorly water-soluble drug component destroying the gel network of the semi-solid preparation.
Therefore, the present invention aims at a semi-solid preparation containing a poorly water-soluble drug and having high heat stability.

The present invention has the following aspects.
[1] Contains (A) a poorly water-soluble drug, (B) mannitol, (C) a gelling agent, and (D) water, and the mass of the component (D) is 50% by mass or less based on the mass of the entire semi-solid preparation. A semi-solid preparation.
[2] The semi-solid preparation according to [1], wherein the mass ratio represented by the component (B) / the component (A) is 0.001 to 0.15.
[3] The semi-solid preparation according to [1] or [2], wherein the component (A) and the component (B) are present as a granulated product containing the component (A) and the component (B).
[4] The semi-solid preparation according to any one of [1] to [3], wherein the component (A) is at least one selected from the group consisting of berberine tannate, ibuprofen, and allylisopropylacetylurea.
[5] The semi-solid preparation according to any one of [1] to [4], wherein the component (C) is at least one selected from the group consisting of gelatin and pectin.

[6] The method for producing a semisolid preparation according to any one of [1] to [5], wherein the component (A) and the component (A) and the component (D) in which the component (C) is dissolved A method for producing a semi-solid preparation, comprising dispersing the component (B).
[7] The method for producing a semi-solid preparation according to [6], comprising forming the component (A) and the component (B) as a granulated product.
[8] The method for producing a semisolid preparation according to [7], wherein the granulated product is formed by a wet granulation method.

  According to the semi-solid preparation of the present invention, high thermal stability can be maintained even when a poorly water-soluble drug is contained.

(Semi-solid preparation)
The semi-solid preparation in the present invention is obtained by gelling a drug component or the like with a water-soluble gelling agent. For example, a preparation having a jelly property or a gummi property is exemplified.
The semi-solid preparation in the present invention is a preparation having a jelly property or a gummy property, and preferably has a jelly strength of 10 to 2000 g. The jelly strength of the semi-solid preparation is more preferably 50 to 2000 g, and further preferably 100 to 1600 g. If the jelly strength of the semi-solid preparation is equal to or higher than the lower limit, the strength of the semi-solid preparation is improved and the ingestion is improved. If the jelly strength of the semi-solid preparation is less than or equal to the above upper limit value, the strength will not be too high, and the dosage will be improved.
According to JIS K6503, the jelly strength in the present invention is a weight (unit: g) when a load is applied to a semi-solid preparation with a 12.7 mm diameter plunger at 10 ° C. and the surface of the semi-solid preparation is pushed down by 4 mm. ).
The semi-solid preparation in the present invention generally includes what is called an oral jelly or tablet.

The semi-solid preparation of the present invention is a composition containing the following components (A) to (D).
<(A) component>
Component (A) is a poorly water-soluble drug. A poorly water-soluble drug is a poorly water-soluble drug component (active ingredient) in a semi-solid preparation. The “poorly water-soluble component” is determined by the solubility measurement method prescribed in the Japanese Pharmacopoeia, from “extremely insoluble (0.1 g / 100 mL or less) to hardly soluble (0.01 g / 100 mL or less) (20 ° C.)”. The compound classified into "is shown. The solubility is measured by a test according to the 16th Japanese Pharmacopoeia.

As the component (A), berberine tannate (solubility 0.01 g / 100 mL or less), ibuprofen (solubility 0.01 g / 100 mL or less), allyl isopropylacetylurea (solubility 0.01 g / 100 mL or less), etenzaamide (solubility 0. 1 g / 100 mL or less), mefenamic acid (solubility 0.01 g / 100 mL or less), sulindac (solubility 0.01 g / 100 mL or less), indomethacin (solubility 0.01 g / 100 mL or less), felbinac (solubility 0.01 g / 100 mL or less) Etodolac (solubility 0.01 g / 100 mL or less), flurbiprofen (solubility 0.01 g / 100 mL or less), ketoprofen (solubility 0.02 g / 100 mL), naproxen (solubility 0.01 g / 100 mL or less), oxaprozin (solubility) 0.01 g / 100 mL), zaltoprofen (solubility 0.01 g / 100 mL or less), piroxicam (solubility 0.01 g / 100 mL or less), meloxicam (solubility 0.01 g / 100 mL or less), lornoxicam (solubility 0.01 g / 100 mL) And the like).
Among these, berberine tannate, ibuprofen, and allyl isopropyl acetylurea are preferable from the viewpoint of improving the thermal stability as a semi-solid preparation.
These may be used individually by 1 type and may use 2 or more types together.

  The content of the component (A) in 100% by mass of the semisolid preparation varies depending on the type of the component (A), and can be appropriately selected according to the type, but is preferably 50% by mass or less. More preferably, the content is 0.01 to 50% by mass. The content of the component (A) is more preferably 0.01 to 30% by mass, and particularly preferably 1.0 to 10% by mass from the viewpoints of doseability and ease of production. If content of (A) component is more than the said lower limit, the effectiveness by (A) component will improve. If content of (A) component is below the said upper limit, there will be no roughness and discomfort at the time of taking, and taking property will improve.

<(B) component>
The component (B) is mannitol. The semi-solid preparation of the present invention has good thermal stability by including the component (B). Generally, when the semi-solid preparation contains the component (A), the gel stability of the semi-solid preparation is destroyed, so that the thermal stability tends to be lowered. On the other hand, the semi-solid preparation of the present invention improves the miscibility of water (component (D)) and component (A) by including component (B), and component (B) destroys the gel network. Suppress. As a result, even if the semisolid preparation contains the component (A), the thermal stability is unlikely to decrease.

The content of the component (B) in the semi-solid preparation is 0.001 to 0.15 in terms of mass ratio represented by the component (B) / component (A) from the viewpoint of ingestion and ease of production. The amount is preferably 0.01 to 0.1, more preferably 0.03 to 0.08.
If the mass ratio represented by (B) component / (A) component is more than the said lower limit, the heat stability of a semi-solid formulation will improve more. If the mass ratio represented by (B) component / (A) component is below the said upper limit, there will be no roughness and discomfort at the time of taking, and taking property will improve.
Moreover, 0.001-5 mass% is preferable and the compounding quantity of (B) component per single dose of a semi-solid preparation has more preferable 0.002-1 mass%.

The component (B) may be contained in the semi-solid preparation as a granulated product containing the component (A) and the component (B). The granulated product has a form in which the component (B) is attached to the surface of the granular component (A). However, there may be a granulated product in which part or all of the component (B) is dissolved in the production process of the semisolid preparation and the component (B) is not attached to the component (A).
The average particle size of the granulated product contained in the semi-solid preparation is preferably 5 to 100 μm, and more preferably 5 to 80 μm.
The particle size of the granulated product contained in the semi-solid preparation is a value obtained by averaging the maximum particle sizes of five arbitrary granulated products in an arbitrary cut surface image of the semi-solid preparation.
Of course, not as a granulated product, the component (A) and the component (B) may be separately dispersed in the semi-solid preparation.

<(C) component>
Component (C) is a gelling agent. (C) A component is for making a semi-solid formulation form a gel so that it may become a jelly state or a gummy state.

Examples of the component (C) include gelatin, pectin, agar, gellan gum, carrageenan, xanthan gum, locust bean gum, guar gum, gellan gum and the like. Among these, gelatin and pectin are preferable, and it is more preferable that both gelatin and pectin are contained. These may be used individually by 1 type and may use 2 or more types together.
There is no restriction | limiting in particular about the kind etc. as gelatin, According to the kind, use, etc. of (A) component and (B) component, it can select suitably. Examples include those derived from bones and skins such as cows and pigs, whales and fish. The gelatin may be acid-treated gelatin (isoelectric point pH 6-9) or alkali-treated gelatin (isoelectric point pH 4.8-5.2). The gelatin jelly strength is preferably 100 g or more, more preferably 150 g or more, and even more preferably 200 g or more. The jelly strength is measured by the method described above.
Pectin is a polysaccharide contained in plants and is mainly composed of polygalacturonic acid partially methylated. As pectin, low methoxyl pectin (LM pectin) in which the proportion of methylated galacturonic acid is less than 50% by mass in the total galacturonic acid, and high methoxyl pectin (HM in which the proportion of methylated galacturonic acid is 50% by mass or more) Pectin) and the like, and HM pectin is preferable.

  As for content of (C) component in 100 mass% of semi-solid preparations, 1-20 mass% is preferable. When the component (C) is gelatin, the content of the component (C) in 100% by mass of the semisolid preparation is preferably 1 to 20% by mass, more preferably 5 to 15% by mass. More preferably, it is -12 mass%. When the component (C) is pectin, the content of the component (C) in 100% by mass of the semisolid preparation is preferably 1 to 20% by mass, more preferably 1 to 15% by mass. More preferably, it is 10 mass%. If content of (C) component in 100 mass% of semi-solid preparations is more than the said lower limit, the intensity | strength of a semi-solid preparation will improve. If content of (C) component in 100 mass% of semi-solid preparations is below the said upper limit, since the intensity | strength of a semi-solid preparation will not become high too much, ingestibility will improve.

<(D) component>
(D) A component is water and is a base material in a semi-solid preparation.

  The content of the component (D) in 100% by mass of the semi-solid preparation is 50% by mass or less, preferably 5 to 50% by mass, and more preferably 10 to 30% by mass. If content of (D) component in 100 mass% of semi-solid preparations is more than the said lower limit, since a semi-solid preparation is hard to collapse into a powder form and is not too hard, taking property improves. If the content of the component (D) in 100% by mass of the semi-solid preparation is not more than the above upper limit value, the semi-solid preparation will not be deformed and divided when it is pinched, so that it is easy to handle and the dosage is improved. To do.

<Optional component>
The semi-solid preparation of the present invention may contain optional components other than the components (A) to (D) as long as the effects of the present invention are not impaired.
Examples of the optional component include medicinal components other than the component (A), for example, drugs dissolved in water (0.1 g / 100 mL or more) and additives.

  Additives include sweeteners (reduced maltose starch syrup, granulated sugar and other white sugar, fructose glucose liquid sugar, honey, sorbitol, erythritol, maltitol, fructose, reduced palatinose, xylitol, aspartame, acesulfame potassium, sucralose, etc.) Agents (sodium edetate, water-soluble polymers, etc.), solubilizers (anionic surfactants, nonionic surfactants, amphoteric surfactants, etc.), solvents (ethanol, glycerol, etc.), polyols (propylene glycol, glycerol, Polyethylene glycol, etc.), preservatives (ethyl paraoxybenzoate, methyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, etc.), antioxidants, flavoring agents / fragrances, cooling agents, colorants, pH adjusters (Citric acid), buffering agents, etc. It is.

(Production method)
One embodiment of the method for producing a semisolid preparation of the present invention will be described.
The manufacturing method of the semi-solid preparation of this embodiment has a mixed solution preparation process which disperse | distributes (A) component and (B) component in (D) component which dissolved (C) component.
When the semi-solid preparation contains a sweetener, the mixed solution preparation step includes a sugar solution manufacturing operation and a mixed solution preparation operation described below. Moreover, the mixed solution preparation process may include the granulated product granulation operation shown below.

<Sugar solution manufacturing operation>
In the sugar solution production operation, the above-mentioned sweetener, for example, reduced maltose starch syrup, sorbitol, granulated sugar and the (D) component are heated and dissolved at about 80 to 140 ° C. and boiled until the water content reaches an arbitrary amount. obtain.

<Granulated product granulation operation>
In the granulation operation, a granulated product containing the component (A) and the component (B) is produced. The granulated product containing the component (A) and the component (B) can be produced by, for example, a dry granulation method or a wet granulation method.
In the wet granulation method, for example, a fluidized bed granulator is used to spray an aqueous solution or dispersion containing the component (B) into the component (A) (optional components may be added as necessary). Then, a granulated product is produced by drying (fluidized bed granulation method).
In the dry granulation method, for example, using a dry granulator, the components (A) and (B) are charged into the dry granulator, and granulated so that the volume average particle diameter is 5 to 100 μm. A granulated product of powder is prepared.
In addition, the manufacturing method of the semi-solid preparation of this invention does not need to include granulated material granulation operation.

<Mixed solution preparation operation>
In the mixed solution preparation operation, a mixed solution in which the component (A) and the component (B) are dispersed in the component (D) in which the component (C) is dissolved is prepared.
Specifically, after the component (C) is swollen in advance with twice the amount of the component (D) with respect to the component (C), it is heated to about 40 to 80 ° C. and dissolved, and the component (D) Alternatively, in addition to the sugar solution obtained by the sugar solution manufacturing operation, the mixture is heated and stirred at about 60 to 140 ° C.
Next, the pH is adjusted with an organic acid such as citric acid, and the granulated product containing the component (A) and the component (B) or the component (A) and the component (B) obtained by granulation operation. In addition, a mixed solution is obtained by stirring and mixing.
The obtained mixed solution may be cooled and used as a semi-solid preparation as it is. Moreover, you may shape | mold a semisolid formulation by the semisolid formulation formation process mentioned later.

<Semi-solid preparation process>
The obtained mixed solution is filled into a starch mold so as to be 800 to 5000 mg per piece, and solidified at room temperature for 6 to 18 hours to obtain a semi-solid preparation.
The obtained semi-solid preparation can be filled into an aluminum pouch, a PTP container, a glass bottle or the like.

  EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated in detail, this invention is not limited by the following description.

(Raw materials used)
<(A) component>
A-1: Berberine tannate (trade name “berberine tannate”, manufactured by Alps Pharmaceutical Co., Ltd.).
A-2: Ibuprofen (trade name “Ibuprofen”, manufactured by BASF Japan Ltd.).
A-3: Allylisopropylacetylurea (trade name “allylisopropylacetylurea”, manufactured by Kongo Pharmaceutical Co., Ltd.)
<(B) component>
B: Mannitol (trade name “PEARLITOL50C”, manufactured by Rocket Japan Co., Ltd.).
<(B ′) component>
B ′: maltitol (trade name “maltitol”, manufactured by Mitsubishi Corporation Foodtech Co., Ltd.).
<(C) component>
C-1: Gelatin (trade name “AP-270”, manufactured by Nippi Corporation).
C-2: Pectin (trade name “USP-HM”, manufactured by Sanki Co., Ltd.).

<Optional component>
Sweetener: Reduced maltose starch syrup (powder) (trade name “Amalty”, manufactured by Mitsubishi Corporation Foodtech Co., Ltd.).
Sweetening agent: sorbitol (trade name “D-sorbitol”, manufactured by Mitsubishi Corporation Food Tech Co., Ltd.).
Sweetener: Granulated sugar (trade name “Granulated Sugar”, manufactured by Mitsui Sugar Co., Ltd.).
pH adjuster: citric acid (trade name “citric acid”, manufactured by Fuso Pharmaceutical Co., Ltd.).
Fragrance: Grapefruit fragrance (trade name “Grapefruit fragrance SY-1521”, manufactured by Takasago Fragrance Co., Ltd.).

(Measurement of jelly strength)
The jelly strength of the semi-solid preparations obtained in Examples 1 to 14 and Comparative Examples 1 to 3 was measured according to JIS K6503. Specifically, at 10 ° C., with a 12.7 mm diameter plunger, a load was applied to the semi-solid preparation, and the weight (unit: g) when the surface of the semi-solid preparation was pushed down by 4 mm was measured. Jelly strength was assumed.

(Thermal stability test)
The semi-solid preparations obtained in Examples 1 to 14 and Comparative Examples 1 to 3 were encapsulated in an aluminum pouch (inner layer: polyethylene), and stored for 1 month at 40 ° C. and 75% humidity. Then, it was allowed to stand until it reached room temperature, the semi-solid preparation taken out from the aluminum pouch was cut with a knife, and the thermal stability was evaluated. The thermal stability was a visual evaluation of the degree of melting (stickiness) of the semi-solid preparation. The evaluation criteria were set as follows, and C evaluation or better was judged as good.
A: Stickiness on the surface and inside is not seen.
B: Surface stickiness is slightly seen, but internal stickiness is not seen.
C: Slight stickiness on the surface and inside is seen.
D: Stickiness on the surface and inside is observed.
E: The prototype of the semi-solid preparation is not retained.

Example 1
In accordance with the formulation shown in Table 1, reduced maltose starch syrup, sorbitol, granulated sugar and component (D) were mixed, dissolved by heating at about 80 to 140 ° C., and boiled until an arbitrary amount of water was obtained (sugar Liquid manufacturing operations). However, the component (D) was 1.2 times the amount described in Table 1.
After swelling the component (C-1) with the component (D) (twice the amount of the component (C-1)), the solution dissolved by heating at about 70 ° C. is added to the sugar solution, and the temperature is 60 to 140 ° C. The mixture was heated and stirred to the extent. Furthermore, (D) component (1 time amount with respect to citric acid) and (A-1) component, (B) component, and 7.5 mg of fragrance | flavor which melt | dissolved 75 mg of citric acid were added, and it stirred and mixed, the mixing | blending shown in Table 1 A mixed solution having a ratio was obtained (mixed solution preparation operation). The obtained mixed solution was filled into a starch mold so as to be 2500 mg per piece and solidified at room temperature for 12 hours to obtain a semi-solid preparation (semi-solid preparation molding step). The heat stability test was performed by filling a semi-solid preparation into an aluminum pouch.

(Example 2)
A sugar solution was produced in the same manner as in Example 1 (sugar solution production operation).
Separately, an aqueous solution for spraying having a concentration of 4% by mass was prepared by dissolving the component (B) in water. Next, using a fluidized bed granulator MP-01 (manufactured by POWREC Co., Ltd.), the spray rate of the aqueous solution for spraying is 20 mL / min, the intake air temperature is 80 ° C., the air volume with respect to 300 g of the raw powder of component (A-1). Spraying of the spraying aqueous solution at 0.6 m ³ / min, and finishing the drying when the exhaust temperature reaches 55 ° C. after the spraying is completed, the mass ratio represented by B / A shown in Table 1 A granulated product was obtained (granulated product granulating operation).
After swelling the component (C-1) with the component (D) (twice the amount of the component (C-1)), the solution dissolved by heating at about 70 ° C. is added to the sugar solution, and the temperature is 60 to 140 ° C. The mixture was heated and stirred to the extent. Furthermore, (D) component (1 time amount with respect to citric acid) which melt | dissolved 75 mg of citric acid, the granulated material obtained by granulation operation, and 7.5 mg of fragrance | flavors were added and stirred and mixed, A mixed solution having a blending ratio shown in 1 was obtained (mixed solution preparation operation). The obtained mixed solution was filled into a starch mold so as to be 2500 mg per piece and solidified at room temperature for 12 hours to obtain a semi-solid preparation (semi-solid preparation molding step). The heat stability test was performed by filling a semi-solid preparation into an aluminum pouch.

(Examples 3 to 7)
A granulated product was produced in the same manner as in Example 2 except that the mass ratio represented by B / A was changed to the value shown in Table 1 in the granulated product granulation operation.
A mixed solution was prepared in the same manner as in Example 2 except that the obtained granulated product was used so that the blending ratio shown in Table 1 was obtained, thereby obtaining a semisolid preparation. The stability test was also performed in the same manner as in Example 2.

(Example 8)
(A-1) component and (B) component are put into a dry granulator (manufactured by Turbo Kogyo Co., Ltd .: roller compactor), and granulation of a powder having a mass ratio represented by B / A shown in Table 2 The product was obtained (granulated product granulation operation).
A mixed solution was prepared in the same manner as in Example 2 except that the obtained granulated product was used so that the blending ratio shown in Table 2 was obtained, and a semi-solid preparation was obtained. The stability test was also performed in the same manner as in Example 2.

(Examples 9 and 10)
In (A), instead of (A-1), (A-2) (Example 9) or (A-3) (Example 10) is used. A granulated product was produced in the same manner as in Example 2 except that the mass ratio was changed to the value shown in Table 2.
A mixed solution was prepared in the same manner as in Example 2 except that the obtained granulated product was used so that the blending ratio shown in Table 2 was obtained, and a semi-solid preparation was obtained. The stability test was also performed in the same manner as in Example 2.

(Examples 11 and 12)
A granulated product was produced in the same manner as in Example 2 except that the mass ratio represented by B / A was changed to the value shown in Table 2 in the granulated product granulation operation.
Table 2 shows the obtained granulated product and (C-2) (Example 11) or (C-1) and (C-2) (Example 12) as the component (C). A mixed solution was prepared in the same manner as in Example 2 except that the mixture ratio was adjusted to obtain a semi-solid preparation. The stability test was also performed in the same manner as in Example 2.

(Example 13)
A granulated product was produced in the same manner as in Example 2 except that the mass ratio represented by B / A was changed to the value shown in Table 2 in the granulated product granulation operation.
A mixed solution was prepared in the same manner as in Example 2 except that the obtained granulated product was used so that the blending ratio shown in Table 2 was obtained, and a semi-solid preparation was obtained. The stability test was also performed in the same manner as in Example 2.

(Example 14)
A granulated product was produced in the same manner as in Example 2 except that the mass ratio represented by B / A was changed to the value shown in Table 2 in the granulated product granulation operation.
A semi-solid preparation was obtained in the same manner as in Example 2 except that the obtained granulated product was used to heat and mix the mixed solution until it became a mixed solution having the blending ratio shown in Table 2. The stability test was also performed in the same manner as in Example 2.

(Comparative Example 1)
A semi-solid preparation was obtained in the same manner as in Example 1 except that a mixed solution having the blending ratio shown in Table 3 was prepared without using the component (B). The thermal stability test was also performed in the same manner as in Example 1.

(Comparative Examples 2 and 3)
Example except that (B ′) component was used instead of component (B) and the mass ratio represented by B / A was changed to the value shown in Table 3 in the granulation operation. A granulated product was produced in the same manner as in No. 2.
A mixed solution was prepared in the same manner as in Example 2 except that the obtained granulated product was used so that the blending ratio shown in Table 3 was obtained, thereby obtaining a semi-solid preparation. The stability test was also performed in the same manner as in Example 2.

  About the semi-solid preparation of each Example and a comparative example, jelly strength was measured and thermal stability was evaluated, and the result is shown in Tables 1-3.

As shown in Tables 1-2, Examples 1-14 had good thermal stability.
From the results of Examples 1 and 6, it was found that when the component (A) and the component (B) were mixed into a semi-solid preparation as a granulated product, the thermal stability was further increased.
From the results of Examples 4 and 8, it can be seen that the granulated product has good thermal stability regardless of whether it is wet or dry, but in the case of wet, the thermal stability is better. It was.
From the results of Examples 9 and 10, it was found that the thermal stability was good even when the component (A) was (A-2) and (A-3).
From the results of Examples 11 and 12, it was found that even the component (C-2) had good thermal stability.
From the results of Examples 13 and 14, it was found that the lower the moisture content, the better the thermal stability, but if it was 50% by mass or less, the thermal stability was good.
In Comparative Example 1 containing no component (B), stickiness was observed on the surface and inside of the semi-solid preparation, and the heat stability was poor.
In Comparative Examples 2 and 3 containing the component (B ′) instead of the component (B), stickiness is observed on the surface and inside of the semi-solid preparation, or the original shape is not retained, and the heat stability is poor. .
From the above results, it was confirmed that by applying the present invention, high heat stability can be maintained even if the semi-solid preparation contains a poorly water-soluble drug.

Claims (5)

  (A) a poorly water-soluble drug, (B) mannitol, (C) a gelling agent, and (D) water, and the mass of the component (D) with respect to the mass of the entire semi-solid preparation is 50% by mass or less. Semi-solid formulation.   The semi-solid preparation according to claim 1, wherein a mass ratio represented by the component (B) / the component (A) is 0.001 to 0.15.   The semi-solid preparation according to claim 1 or 2, wherein the component (A) and the component (B) are present as a granulated product. It is a manufacturing method of the semisolid preparation according to any one of claims 1 to 3,
A method for producing a semi-solid preparation, comprising dispersing the component (A) and the component (B) in the component (D) in which the component (C) is dissolved.   The manufacturing method of the semi-solid preparation of Claim 4 which has forming the said (A) component and the said (B) component as a granulated material.