JP2003104881A - Suspension for internal application - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a suspension for an internal application containing ibuprofen and gelatinized starch. SOLUTION: The suspension contains ibuprofen stable for a long period and keeping the property even by the addition of a sweetener. Accordingly, the liquid has reduced stimulation and bitter taste of ibuprofen and is easy to drink and useful as antipyretic analgesic liquid and combination cold remedy liquid takable even by aged persons and child.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a suspension for oral administration which contains ibuprofen, is excellent in dispersion stability and has reduced irritation and bitterness and is easy to take.

[0002]

BACKGROUND OF THE INVENTION Ibuprofen is widely used as an analgesic, antipyretic, general cold remedy, etc. because of its excellent anti-inflammatory and analgesic / antipyretic action. But ibuprofen stimulates,
Since it has a bitter taste and has low solubility in water, it has been conventionally applied to preparations such as tablets and granules in which taste masking is easy.

However, in recent years, the liquid medicine for internal use is preferable in consideration of the taking ability for the elderly and children. Therefore, attempts have been made to use ibuprofen as an internal liquid preparation, and for example, for the purpose of masking taste, Japanese Patent No. 2847134, Japanese Patent Laid-Open No. 8-333245, and Japanese Patent Laid-Open No. 8-333.
No. 246, JP-A-8-333265, and JP-A-8-337524 are reported.

[0004]

In order to use ibuprofen as a liquid preparation for oral administration, a sweetener is often added to mask irritation when taking ibuprofen, for example, 30 mL in JP-A-8-333245. Medium 10
g of sweetener is used. However, it has been found that such a large amount of sweetener increases the specific gravity of the liquid and the suspended ibuprofen particles float to the liquid surface. On the other hand, if the content of the sweetener is small, the specific gravity of the liquid is small, and the suspended ibuprofen particles will settle to the bottom of the container. It was also found that when the ibuprofen particles were aggregated or solidified at the bottom of the container when they settled to the bottom of the container, redispersion became difficult. It was also found that when the ibuprofen floated on the liquid surface, the ibuprofen was exposed to the air on the liquid surface and dried, and adhered to the periphery of the container in a short time.

Therefore, an object of the present invention is to contain ibuprofen, which maintains a suspended state for a long period of time and can be easily redispersed without being aggregated or solidified at the bottom of a container even if it is once settled. To provide a suspension for internal use.

[0006]

The inventors of the present invention have conducted various investigations for a dispersant capable of stabilizing the suspension of ibuprofen, and as a result, the use of pregelatinized starch has no need to incorporate a surfactant. It was also found that ibuprofen maintains a stable suspended state for a long period of time, can be easily redispersed even once separated, and retains these effects even if a sweetener is added, and completes the present invention. Came to.

That is, the present invention relates to ibuprofen and α
The present invention provides a suspension for internal use containing modified starch.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the suspension for oral administration of the present invention, ibuprofen is 0.1 to 10 W / V%, more preferably 0.25 to 5.0 w / v from the viewpoint of efficacy, irritation and dispersion stability.
%, Particularly 0.5 to 2.0 w / v% is preferable. Further, ibuprofen is preferably used after being pulverized, but if it is made too fine, irritation becomes strong, so that the particle diameter is particularly preferably 10 to 200 μm. The pulverization may be performed with ibuprofen alone, as a mixture with other medicinal ingredients, or with an excipient such as purified sucrose.

The pregelatinized starch is obtained by heating starch to be completely pregelatinized. Pregelatinization of starch is disrupted by heating to break the hydrogen bonds maintained by micelles, that is, the regular arrangement of the chains of amylose, causing water molecules to enter between the micelles, causing them to collapse and expand. Is to be in a state. The pregelatinized starch is obtained, for example, by heating wheat starch, corn starch, potato starch and the like with water to pregelatinize and rapidly drying. Of these, pregelatinized starch derived from potato starch is particularly preferable. As a commercial product,
For example, Amycol (trade name, manufactured by Nitto Chemical Co., Ltd.), matsunoline (trade name, manufactured by Matsutani Chemical Co., Ltd.), or pregelatinized starch (trade name, manufactured by Freund Industrial Co., Ltd.) can be used. From the viewpoint of dispersion stability of ibuprofen, the content is 0.1 to 1.0 W / V%, more preferably 0.25 to 5.0 W / V%, and particularly 0.5 to 1.0 W / V in the suspension agent. V
% Is preferred. In the present invention, pregelatinized starch may be mixed with ibuprofen and other components to prepare a suspension for internal use. However, after starch is dissolved and heated until the starch is completely pregelatinized, ibuprofen is then added. By adding other components, pregelatinized starch may be used in the preparation process of the preparation of the present invention.

The suspension for internal use of the present invention preferably further contains xanthan gum from the viewpoint of dispersion stability. Xanthan gum is a natural gum substance obtained by purifying a fermented polysaccharide, and there are a clear soluble type and an opaque dispersed type in water, which may be used in the present invention, or may be used in combination. Good. Examples of commercially available products include Echo Gum (trade name, manufactured by Dainippon Pharmaceutical), Neosoft (trade name, manufactured by Kojin), Rhodigel (trade name, manufactured by Rhone Poulin Japan), or xanthan gum (trade name, Saneigen F / F).・ Made by Ai) or the like can be used. From the viewpoint of dispersion stability, the content of these xanthan gums is 0.1 to 0.5 W / V%, particularly 0.2 to 0.4 W in the suspension agent.
/ V% is preferable.

In addition to the above-mentioned components, the suspension of the present invention is a pharmaceutical additive usually used in medicine, such as pH.
Modifiers, other thickeners, sweeteners, preservatives, flavors, stabilizers, other dispersants, suspension stabilizers, water and the like can be added. Examples of suspension stabilizers include anhydrous citric acid and sodium citrate. As the sweetener, for example, purified sucrose, glucose, fructose, monosaccharides or oligosaccharides such as trehalose, erythritol, xylitol, sugar alcohol such as sorbitol, stevia,
Examples thereof include, but are not limited to, glycyrrhizic acid and its salts, natural sweeteners such as thaumatin, synthetic sweeteners such as saccharin, sodium saccharin and sucralose, and amino acid sweeteners such as aspartame.

The pH of the suspension of the present invention is 2-5, especially 2
It is desirable to adjust to ~ 4 for stable storage.
At this time, various buffers that can be used as additives for pharmaceuticals can be used as the pH adjuster.

Surfactants generally have a peculiar odor and bitterness, and many of them decompose at pH 4 or less, which is particularly difficult to use in liquid preparations. On the other hand, the suspension agent of the present invention has excellent dispersion stability even if such a conventional surfactant is not blended, and it is not necessary to blend the surfactant substantially.

The suspension of the present invention contains ibuprofen as a medicinal component, and if necessary, other antipyretic analgesics, muscle relaxants, antispasmodics, antihistamines, sympathomimetics, various vitamins, antitussives, expectorants. Agents, crude drugs and Chinese herbs can be mixed.

The suspension agent of the present invention is, for example, 80 ° C. or higher,
Preferably, pregelatinized starch and other additives are added to and dissolved in water at 80 to 95 ° C, and then cooled to 60 ° C or lower, preferably room temperature to 60 ° C, to which ibuprofen and other medicinal components are directly or previously prepared. It is preferably produced by suspending in water, adding and then uniformly dispersing.

[0016]

The present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

Examples 1 to 5 and Comparative Examples 1 to 3 Suspension agents of Examples 1 to 5 and Comparative Examples 1 to 3 were produced according to the formulations shown in Tables 1 to 3. Purified water is heated to 80 ° C or higher and 95 ° C or lower, propyl gallate, saccharides, xanthan gum and pregelatinized starch are sequentially dissolved with stirring, and then cooled to 60 ° C or lower and room temperature or higher. At this time, the sugar, xanthan gum and pregelatinized starch may be mixed in advance. To this solution, a solution in which other drug is dissolved and a water-insoluble or poorly water-soluble drug is suspended is added and uniformly dispersed.

[0018]

[Table 1]

[0019]

[Table 2]

Dispersion stability test: Using the suspensions prepared in the above Examples and Comparative Examples, a dispersion stability test and a redispersibility test were conducted.

(Test method) 50 mL of a suspension agent immediately after production
In a 50 mL graduated cylinder, 40 ℃ and 50 ℃
After standing at each temperature, the height of the supernatant was read and the ratio to the total liquid height was calculated (water separation rate). Moreover, when the suspended particles floated on the liquid surface, it was designated as “floating”. Redispersion was performed on samples that had taken off or floated on the last day of the observation period. When the graduated cylinder was slowly turned upside down 3 times, the suspended particles were visually uniformly dispersed and no aggregation of particles was observed. The redispersibility was "good". The redispersibility was "poor" when the suspended particles were not visually uniform or the particles were aggregated even if they were uniform.

(Results) The results are shown in Tables 3 and 4.

From the results shown in Tables 3 and 4, 40 ° C. was obtained in Comparative Example 1 in which both xanthan gum and pregelatinized starch were omitted.
Also, the suspended particles floated up to 4 months at 50 ° C., and it can be said that the dispersion stability is extremely poor. Also in Comparative Example 2 in which only xanthan gum was blended, suspended particles floated after 50 ° C. for 2 months, and the dispersion stability was poor. In addition, in Comparative Example 3 in which starch solubilized by acid decomposition was added instead of pregelatinized starch and xantham gum was added, suspended particles floated after 2 weeks at 50 ° C., and it can be said that the dispersion stability is extremely poor. In addition, Comparative Examples 1, 2 and 3 were also poor in redispersibility.

On the other hand, in Examples 1 to 5, although water was released up to 4 months at 50 ° C., suspended particles did not float and the redispersibility was good. Dispersion was maintained in Examples 3 and 5 up to 40 ° C. for 4 months, and redispersibility was also good in Examples 1, 2 and 4 after water separation. From the above, in Examples 1 to 5, by adding the pregelatinized starch,
Compared to Comparative Examples 1, 2 and 3, the dispersion is stable, the redispersibility is good, and it is easy to take.

[0025]

[Table 3]

[0026]

[Table 4]

[0027]

INDUSTRIAL APPLICABILITY The suspension of the present invention has a stable suspension of ibuprofen for a long period of time, and since this state is maintained even if a sweetener is added, irritation and bitterness of ibuprofen are reduced, and it can be drunk. Since it is easy, it is useful as an antipyretic analgesic solution, a general cold solution, etc. that can be taken by the elderly and children.

   ─────────────────────────────────────────────────── ─── Continued front page    F term (reference) 4C076 AA16 BB01 CC04 CC15 EE30F                       EE38F FF16 FF36 FF43                       FF52 FF66 FF68                 4C206 AA01 AA02 DA24 KA01 MA02                       MA03 MA05 MA41 MA72 NA03                       NA09 NA10 ZA07 ZA08 ZA59                       ZB11

Claims (6)

[Claims] 1. A suspension for internal use containing ibuprofen and pregelatinized starch. 2. The ibuprofen content is 0.1 to 10 W.
/ V% and the content of pregelatinized starch is 0.1 to 10 W
The suspension for internal use according to claim 1, which is / V%. 3. The suspension for internal use according to claim 1 or 2, which further contains xanthan gum. 4. The content of xanthan gum is 0.1 to 0.
The suspension for internal use according to any one of claims 1 to 3, which is 5 W / V%. 5. The suspension for internal use according to any one of claims 1 to 4, which has a pH of 2 to 5. 6. The internal-use suspension agent according to claim 1, which does not contain a surfactant.