JPH0426618A - Troche - Google Patents

Abstract

PURPOSE:To provide a troche containing ibuprofen singly or in combination with cyclodextrin and effective in mitigating the laryngeal inflammation and pain by the direct action to the oral mucosa and laryngeal mucosa. CONSTITUTION:The objective troche contains 10-50mg (preferably 5-30mg) of ibuprofen which is a non-steroidal analgesic anti-inflammatory agent and, as necessary, 2-10 pts.wt. (preferably 4-6 pts.wt.) of cyclodextrin based on 1 pt.wt. of ibuprofen. An excellent remedying effect can be attained in spite of low content of the drug component compared with a commercially available peroral drug and the troche has decreased stimulation.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a lozenge containing ibuprofen alone or ibuprofen and cyclodextrin.

[Prior Art] Ibuprofen preparations are non-steroidal analgesic and anti-inflammatory agents, and are relatively safe drugs that are widely used for oral administration. However, ibuprofen itself has low solubility in water, and has a specific taste and a unique pungent odor that strongly irritate the tip of the tongue, so it is not always easy to formulate various dosage forms.

In order to improve these drawbacks, for example, oral preparations using cyclodextrins were developed in Japanese Patent Application Laid-Open No. 55-92.
No. 341 and No. 56-46837, etc., but no concrete knowledge has yet been found regarding other dosage forms, especially those for intraoral use, and they have not yet been put to practical use.

In addition, it is known that oral preparations of ibuprofen are quickly absorbed from the gastrointestinal tract after administration and enter the circulating bloodstream, where they are then delivered to the site of action and exert their effects. Even if you take it for the purpose of suppressing pain,
The amount of drug delivered to the site of inflammation is extremely small compared to the dose, and in order to improve local symptoms, it is necessary to take a larger amount of drug than is originally necessary.

[Problems to be Solved by the Invention] The present inventors attempted to apply (contact) ibuprofen directly to the oral mucosa, pharyngeal mucosa, etc. for the purpose of treating inflammation and pain in the pharynx and larynx. A lozenge with good therapeutic effects and reduced irritation despite a smaller amount of drug compared to oral formulations (75 or 100 mg/tablet, maximum daily dose of 450 to 600 mg) The present invention was successfully completed.

That is, an object of the present invention is to provide a troche containing ibuprofen alone or ibuprofen and cyclodextrin.

[Means for Solving the Problems] The lozenge according to the present invention contains ibuprofen alone or ibuprofen and cyclodextrin, and the amount of ibuprofen used as an active ingredient is 1 to 50 Il per tablet, preferably 5 to 50 Il per tablet. It is 30 mg. That is, when used as a lozenge, if the ibuprofen content is less than 1 mg, the effect may be insufficient.
Moreover, if it exceeds 50 mg, the irritating bitterness peculiar to ibuprofen becomes strong, making it unsuitable for practical use.

In the present invention, if the ibuprofen content per lozenge is low, cyclodextrin is not necessarily required, but if the content is high, the irritant bitterness characteristic of ibuprofen is enhanced, so irritation is reduced. It is necessary to add cyclodextrin for the purpose of (improving taste).

The cyclodextrin used in this case is
Either α-1β- or γ-type cyclodextrin can be used, and is usually used in an amount of 2 to 10 parts by weight, preferably 4 to 6 parts by weight, per 1 part by weight of ibuprofen.

Examples of how cyclodextrin is used include adding and mixing it in the same way as excipients and other additives used in the production of lozenges, or including it using a solution method or kneading method. .

Among these, inclusion by the solution method involves adding ibuprofen as it is or a solution dissolved in an alcoholic solvent to an aqueous solution of cyclodextrin, and mixing and stirring, while inclusion by the crosstalk method involves adding water to cyclodextrin. to make a paste, add ibuprofen powder corresponding to the clathrate equivalent, thoroughly knead using a kneader-1 mortar, etc., and then dry the paste to obtain a powdered clathrate compound. can.

Furthermore, by using cyclodextrin together with saccharides used as excipients when manufacturing lozenges, the irritant bitterness characteristic of ibuprofen can be completely removed.

Furthermore, in the present invention, when the content of ibuprofen is low, the irritation-reducing effect can be obtained by blending saccharides used as excipients without using cyclodextrin. In this case, the amount of saccharide used is 70 to 99.5 parts by weight, preferably 85 to 95 parts by weight, per 1 part by weight of ibuprofen.

The lozenge of the present invention does not require any special operations in its manufacturing method, and can be produced in accordance with conventional methods.

For example, ibuprofen as it is, or with an excipient, a binder, or other suitable additives, and if necessary, water or an organic solvent may be added, and the mixture may be homogeneously mixed and then directly compression-molded, or it may be made into granules. It is then manufactured by adding lubricants and compression molding.

Sugars are mainly used as excipients, and white sugar, powdered sugar, lactose, fructose, starch syrup, reduced maltose, D-mannitol, D-sorbitol, sucrose, etc. are used alone or in combination of two or more.

Further, as the binder, polyvinylpyrrolidone, hydroxypropyl cellulose, corn starch, gelatin, gum arabic, etc. are used, and as the lubricant, magnesium stearate, talc, silosaccharide fatty acid esters, etc. are appropriately selected and used.

Furthermore, as a flavoring agent that is added as necessary for the purpose of improving ease of administration, organic acids such as citric acid, tartaric acid, fumaric acid, ascorbic acid, and malic acid, glycyrrhizin, and menthol are added, and as a flavoring agent, natural or synthetic fragrances are used. etc. are selected and used as appropriate.

The amounts of these additives used are within the range of amounts normally used in the manufacture of lozenges, unless otherwise specified.

[Examples and Test Examples] The present invention will be described in more detail below with reference to Examples and Test Examples.

Example 1 After thoroughly mixing 1.3 g of ibuprofen, 82.0 g of powdered sugar, and 16.4 g of D-mannitol, 0.3 g of magnesium stearate was added and gently mixed again. The obtained powder was molded into a molding machine (diameter 10 mm, molding pressure 3t,
305ec) to obtain 250 lozenges each containing 400 mg (containing 5.2B of ibuprofen).

Example 2 Ibuprofen 2.7. After thoroughly mixing 76.6 g of powdered sugar, 15.4 g of D-mannitol, and 5.0 g of citric acid, 0.3 g of magnesium stearate was added and gently mixed again. The obtained powder was molded into a molding machine (diameter 1
0mm, molding pressure 3t, 305ec) 1 tablet 40'
250 lozenges of 0 m4 (containing 10.8 B of ibuprofen) were obtained.

Example 3 After thoroughly mixing 5.4 g of ibuprofen, 4 g of powdered sugar 7B, 15.7 g of mannitol, and 0.2 g of menthol, 0.3 g of magnesium stearate was added and gently mixed again. The obtained powder was molded into a molding machine (diameter 1
0mm, molding pressure 3t, 305ec), 1 tablet 400
+ng (containing 21.6 mg of ibuprofen) 250 lozenges were obtained.

Example 4 1.5 g of ibuprofen and 8 β-cyclodextrin
．． Add 2g and mix thoroughly in a mortar. This powder contains powder @175.0g, D-mannitol 15.0g
After adding and mixing thoroughly, add 0.0% magnesium stearate.
3g was added and gently mixed again. The obtained powder was molded into a molding machine (diameter 20mm, molding pressure 5t, 305ec)
Using this method, 50 lozenges of 2.0 g (containing 30.0 mg of ibuprofen) were obtained.

Example 5 8.2 g of β-cyclodextrin was added to a solution of 1.5 g of ibuprofen dissolved in 10 ml of ethanol and 20 ml of warm water.
After mixing and stirring the solution dissolved in 0 ml, the solution was concentrated to dryness under reduced pressure. The obtained crystalline material was placed in a mortar and thoroughly mixed and ground to obtain a powder. Powdered sugar 75. After adding 15.0 g of Og, D-mannitol and thoroughly mixing, 0.3 g of magnesium stearate was added and gently mixed again. The obtained powder was molded into 2 tablets using a molding machine (diameter 20 mm, molding pressure 5 tons, 30 seconds). Fifty lozenges of Cog (containing 30.01 g of ibuprofen) were obtained.

Example 6 50 ml of purified water was added to 80 g of starch syrup, and 16.5 K of β-cyclodextrin was further added, followed by dissolution and mixing. Next, heat and dissolve with stirring until just before caramelization (approximately 147°C).
) to stop heating. This was cooled to about 120° C. or lower, 3.0 g of ibuprofen was added, and thoroughly kneaded. This was left to stand and cooled to around room temperature, and powdered in a mortar (pulverizer). Then magnesium stearate 0. 6
g and gently mixed again. The resulting powder was molded into 100 lozenges each weighing 2.0 g (containing 30 mg of ibuprofen) using a molding device (diameter 20 m, molding pressure 57, 305 ec).

Test Example 1 11 plates of indigo blood (Method) Following the same operating procedure as Examples 1 to 6,
Ibuprofen 1.5.10.20.30 and 50 m
Taste stimulation was tested by 6 or 7 panelists using each lozenge obtained at the addition level of g/tablet.

(Results) Shown in Tables 1 to 6.

As is clear from the table, it was observed that even when the ibuprofen content was high, the irritation of ibuprofen was reduced by adding cyclodextrin.

Note that the numerical values for the degree of stimulation are as follows.

+2=I feel a lot of stimulation +1=I feel a little stimulation 0: I don't know - I don't feel much stimulation -2=I don't feel any stimulation Table 1 (Formulation of Example 1) Table 2 (Formulation of Example 2) Table 3 ( (Preparation of Example 3) 112 = Table 5 (Preparation of Example 5) = 13 - Test Example 2 11 Nattoba 11 (Method) Lozenges (ibuprofen) obtained according to the same operating procedure as Examples 1 and 4 5 and Long) was administered one tablet at a time to 8 subjects (4 subjects each) who had symptoms of pain in the pharynx region or hoarseness due to colds, etc., and the therapeutic effects thereof were investigated.

(Results) Shown in Table 7.

As is clear from the table, most of the subjects experienced effects such as alleviating pain symptoms and improving their voice.

The symbols used in effect determination are as follows.

A: Very good B: Fairly good C: Good D=Slightly good E: No effect Table 7 [Effect of the invention] The lozenge containing ibuprofen according to the present invention has a content in one tablet that is lower than that of the commercially available oral Although the amount is small compared to other preparations, it is a highly safe drug that can alleviate inflammation and pain in the pharynx and larynx by acting directly on the oral mucosa and pharyngeal mucosa, and has no side effects.

Patent applicant: Japan Tobacco Inc.

Claims (1)

[Claims] 1. A lozenge containing ibuprofen. 2. A lozenge containing ibuprofen and cyclodextrin. 3. The lozenge according to claim 1 or 2, which contains 1 to 50 mg of ibuprofen. 4. The lozenge according to claim 2 or 3, which contains 2 to 10 parts by weight of cyclodextrin per 1 part by weight of ibuprofen.