JP2002275054A - Easily administrable solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid preparation suppressing sliminess feeling and feeling of adhesion to the oral cavity in taking, which is slippery, easily administrable for an infant, an aged and a patient of swallowing difficulty, or the like, and is easily producible by utilizing a conventional coating method. SOLUTION: The composition of the easily administrable solid preparation includes (a) 5-25 pts.wt. of a gelling agent, (b) 5-25 pts.wt. of a binder and (c) 40-90 pts.wt. of a sugar alcohol based on 100 pts.wt. of the total of a coating layer. The invention includes the solid preparation coated with the coating composition and the production method for the solid preparation by dissolving the coating composition in water, or the like, in the concentration of 3-50 wt.% of the coating composition per 100 pts.wt. of the solid content of the coating, coating the solid materials with the solution and then drying.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for easy-to-take coating of an oral solid preparation. More specifically, the present invention relates to an easy-to-take coating composition containing a gelling agent, a binder and a sugar alcohol, which can be swallowed smoothly when taking an oral solid preparation, and a solid preparation coated with the composition.

[0002]

2. Description of the Related Art In Japan, the average life expectancy is increasing year by year and the society is aging, and in the medical field, the number of medications for elderly patients is increasing, and further increase is expected in the future. Have been. At present, oral pharmaceuticals account for a large proportion of pharmaceuticals, and solid pharmaceuticals are the mainstream, but the problem is that with oral disabilities, it is difficult for elderly people to take oral medications due to poor vision and reduced motor function. Has also increased. Tablets occupy the mainstream of solid preparations, but tablets are sometimes difficult to take for elderly people, and often difficult for children and patients with reduced swallowing function to take.

In order to solve such problems, orally disintegrating tablets and jelly-like preparations have already been developed and sold as preparations which are friendly to the elderly. However, these preparations are not affected by the physical properties of the main drug. Therefore, there are various problems that must be solved in practical use, such as causing problems in formulation and difficulty in industrialization.

[0004] As for the coating of tablets generally used as solid preparations, film tablets and sugar-coated tablets are predominant, and film tablets are said to be simple to produce and have a short production process time because the weight of the film layer is small. It is used more than dragees because of its economic advantages. However, for film tablets, hydroxypropylmethylcellulose (HPMC) or the like, which is widely used as a film base material, has an unpleasant slimy or sticky feeling (or "stickiness") characteristic of celluloses when taken by patients. )) Occur in the oral cavity, making swallowing difficult and causing pain for the patient. Sugar-coated tablets, on the other hand, have no slimy or sticky sensation in the mouth and are generally said to be easy to drink, but due to the heavy weight of the sugar-coated layer, the tablet size is large, making them unsuitable for coating large tablets. In addition, there are disadvantages that the production process time is long, the production is complicated, and the economy is poor.

[0005] As a method for improving the ingestibility of tablets, it is known to use a gelling agent as a coating base. For example, JP-A-9-104621 discloses a gelling agent and a lubricating agent. A drug is described in which a lubricant is coated around the main drug, so that it can be easily taken by elderly people who have a weak swallowing power. It describes a drug-containing substance that is easily wrapped in a substance and easily taken in from the mouth without water or the like. However, JP-A-9-104621 discloses a gelling agent, a lubricant, a specific combination of a lubricant, a production method thereof, and a gelling agent, a binder, and a sugar alcohol of the present invention described below. No specific combination or production method is described at all.
Japanese Patent Application No. 0-7589 does not disclose any specific components of the coating layer and no specific production method thereof.

Further, Japanese Patent Application Laid-Open No. Hei 8-143473 discloses a dry-coated tablet characterized in that a rapidly disintegrating compression coating layer is provided around an easily swallowable inner core containing a pharmaceutically active ingredient. Formulations for oral administration have been described. However, the compression-coated tablet described in the above publication, in which tableting is performed using the coating layer as a compression coating layer, is not practical because the operation is more complicated than in the case of manufacturing with a normal tableting machine, and a dedicated tableting machine is used. Doing so is also economically disadvantageous.

On the other hand, WO 99/22769 describes preparations coated with gellan gum, one of gelling agents, and use of gellan gum as a coating agent. However, although the publication describes the use of gellan gum as a gelling agent, when a tablet is coated with an aqueous solution to which a saccharide is added as a component other than gellan gum, for example, such a coating composition is used to form a tablet. Has a problem that the adhesive force of the coating is weak and the coating layer is generally peeled off from the tablet. Also, as described in the publication, the addition of sodium citrate alone results in a slow film increase rate,
It is not practical to coat a sufficient weight as a normal film, and it is necessary to coat the tablets in advance, and this leads to an increase in the number of production steps, which is not economical. Also, simply adding hydroxypropylmethylcellulose (HPMC) described in the publication as a binder to increase the adhesive force of the gellan gum aqueous solution produces a slimy feeling and an adhesive feeling ("stickiness") of the celluloses, and is easy to drink. It is hard to say. In addition, the combination of gellan gum, sucrose and HPMC tends to cause sticking of the tablets during coating, resulting in manufacturing problems.

[0008]

Means for Solving the Problems As described above, the present inventors have made intensive studies to solve various problems of conventionally known easy-to-drink formulations, and as a result, have found that a gelling agent, a binder, and a sugar A composition containing alcohol in a specific ratio facilitates swallowing of the solid preparation, enabling the solid preparation to exhibit performance that is easy for patients to take, and is easily coated using a conventional coating method. It has been found that a solid preparation can be manufactured.

According to the present invention, a coating composition for easy-to-wear containing the following component compositions a), b) and c), based on 100 parts by weight of the total coating layer, a) a gelling agent 5 to 25 parts by weight, b) 5 to 25 parts by weight of binder, c) 40 to 90 parts by weight of sugar alcohol.

And a solid preparation coated with the above composition for easy-to-take coating, and a) a gelling agent of 5 to 25 with the total amount of the coating layer being 100 parts by weight.
Parts by weight of a composition comprising b) 5 to 25 parts by weight of a binder and c) 40 to 90 parts by weight of a sugar alcohol, at a weight concentration of 3 to 5 parts per 100 parts by weight of solids to be coated.
0% by weight is dissolved in water alone or a mixed solvent of water and alcohol to form a coating solution, and a non-pre-coated solid or a pre-coated solid is coated with the coating solution and then dried. A method for producing a solid preparation is provided.

Hereinafter, terms of the present invention will be described.

[0012] The gelling agent means a base material that gels by containing water, and includes, for example, xanthan gum, tamarind gum, carrageenan, locust bean gum, gellan gum, and agar, with xanthan gum and gellan gum being preferred. One or more of these gelling agents are selected as necessary.

The term "binder" means a substance which has a binding force when dissolved in water. Examples of such a binder include pullulan, hydroxypropylmethylcellulose, hydroxypropylcellulose and methylcellulose. Pullulan is preferred. One or two or more are selected depending on the situation.

Specific examples of the sugar alcohol include mannitol, erythritol, xylitol, and sorbitol. Mannitol is preferred, and one or more of these sugar alcohols are selected as necessary.

The composition for easy-to-take coating according to the present invention, when used as a coating layer, usually contains the following component composition based on 100 parts by weight of the total coating. a) 5-25 parts by weight of a gelling agent b) 5-25 parts by weight of a binder c) 40-90 parts by weight of a sugar alcohol

Preferably, the composition contains the following components. a-1) 10-20 parts by weight of gelling agent B-1) 10-20 parts by weight of binder C-1) 50-80 parts by weight of sugar alcohol

More preferably, the composition contains the following components. a-2) Gelling agent 12 to 18 parts by weight b-2) Binder 12 to 18 parts by weight c-2) Sugar alcohol 60 to 70 parts by weight

Accordingly, a particularly preferred embodiment is a composition containing the following components. a-3) Xanthan gum or gellan gum 12-18
Parts by weight b-3) pullulan 12 to 18 parts by weight c-3) mannitol 60 to 70 parts by weight

Various auxiliaries can be added to the composition of the present invention, if necessary, such as lubricants such as titanium oxide and talc, coloring agents, plasticizers, surfactants, sweeteners and flavoring agents. ,
One or more odorants, fragrances, and other auxiliaries may be added as necessary, but it is preferable to add at least one lubricant. These components are usually used in an amount of not more than half of the total amount of the coating layer, and preferably not more than 30 parts by weight.

Thus, for example, as another preferred form,
A composition containing the following composition components with the total amount of the coating being 100 parts by weight is exemplified. a-4) 10-20 parts by weight of a gelling agent b-4) 10-20 parts by weight of a binder c-4) 40-60 parts by weight of a sugar alcohol d) 10-30 parts by weight of a lubricant

The composition of the present invention may further contain a clinically effective active drug (hereinafter simply referred to as “drug”), but may be a non-precoated solid or a precoated solid described below. It is preferable to preliminarily contain a drug.

Any drug can be added to the composition or solid preparation of the present invention as long as it can be formulated as a usual solid preparation. For example, anti-inflammatory analgesic acetaminophen, ketoprofen, antiallergic agent Diphenhydramine, ebastine, erythromycin and sparfloxacin, antibiotics and antibacterials,
Alacepril, a CE inhibitory antihypertensive, mosapride citrate, a gastrointestinal motility promoter, berberine hydrochloride or its salts, anti-psychotic, haloperidol, an antipsychotic, nitrazepam, an anxiolytic, antidepressant Certain imipramine, moclobemide, antiepileptic phenytoin, zonisamide, sodium valproate, anti-ulcer agent farnesol, bronchodilator ephedrine hydrochloride or salts thereof, antitussive codeine phosphate,
Examples thereof include acid addition salts of morphine such as morphine hydrochloride and morphine sulfate which are narcotic analgesics, brotizolam which is a hypnotic, verapamil and diltiazem which are therapeutic agents for angina, and gliclazide which is a hypoglycemic agent. Furthermore, the present invention is not limited to these drugs, and solid preparations and solids coated with the composition of the present invention can also be used for over-the-counter drugs (OTC drugs) and health foods.

The solids coated with the coating composition of the present invention are oral solids, tablets,
Examples include pills, capsules, granules, powders, crystal powders, etc., and tablets and pills are preferred. These solids can be produced by a conventional method according to a method of producing tablets, pills, capsules, granules, powders and the like. The solid may be a non-precoated solid (for example, an uncoated tablet in the case of a tablet), or may be a solid coated in advance for the purpose of controlling release of an enteric film or the like or for another purpose (hereinafter referred to as “precoated”). May be referred to as "coated solids"). The solid to be coated usually contains a drug, but may be a placebo (eg, lactose) as a mimic.

The method of preparing the composition of the present invention into a coating solution is to dissolve the composition in water alone or a mixed solvent of water and an alcohol such as ethanol, but water is preferred in view of discharge into the environment. . In the dissolution method, the solution may be stirred by hand, but a mechanical mixing device such as a stirrer can also be used, and the solution can be obtained by heating as necessary. The concentration of the coating solution is usually
For 100 parts by weight of solid material to be coated, 3
Although it can be used at ５０50% by weight, 5 to 40% by weight is preferred, and 5 to 20% by weight is more preferred.

The above-mentioned coating solution is solid (for example,
As a method for coating tablets), a pan coating device, a fluidized bed coating device, a vented rotary drum device, and the like can be used, but a vented rotary drum coating device is preferably used. The coating liquid can be supplied continuously by using a spray nozzle or intermittently by supplying a fixed amount of the coating liquid at a time. It is preferable to supply continuously using a nozzle.

The amount of the coating layer is appropriately adjusted depending on the type, size, shape, and the like of the solid material to be coated (hereinafter, also referred to as “non-precoated solid material or precoated solid material”). However, if the weight of the solid material to be coated is 100 parts by weight, it is preferably 0.5 to 50 parts by weight, more preferably 1 to 30 parts by weight. The preparation coated with the composition of the present invention can be subjected to a polishing operation by a conventionally known method.

[0027] Oral solid preparations are usually taken with water, but in the case of elderly people, children or patients with reduced swallowing function, they only swallow water when taking tablets or the like with water. Tablets may remain in the mouth or pharynx. In addition, in the case of a patient whose water intake is restricted due to a disease, the amount of water to be taken must be restricted, and in this case, it is difficult to take the water.

According to the present invention, an unprecoated solid or a precoated solid (eg, a tablet,
Pills, capsules, and granules) with a composition containing a gelling agent, a binder, and a sugar alcohol in a specific ratio, so that when the coated tablet gets wet with a small amount of water, it becomes slimy or sticky. Since a coating layer having no feeling and rich in lubricity is formed, swallowing of the oral solid preparation can be facilitated. Therefore, when the coating composition of the present invention is used, swallowing of the oral solid preparation becomes easy, and the amount of water to be taken for patients such as children, elderly people or patients with reduced swallowing function, as well as elderly people, is also increased. It is also clinically useful for dosing patients with limited fluid intake, such as reducing the burden of continuous dosing. In particular, it is useful for the patient to improve the compliance with the medication instruction from the doctor. Further, the solid preparation produced by coating the coating composition of the present invention has an advantage that it has an excellent feeling of taking without increasing the coating weight as compared with a sugar-coated tablet.

In addition, the method for producing a solid preparation by coating the coating composition of the present invention into a solid preparation can be carried out in the same manner as in the conventional film coating. Can be.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.

[0031]

[Example] Reference example : Solid material to be coated (uncoated tablet)
Production of lactose (DMV) 6 as a solid material to be coated
9 parts by weight, corn starch (manufactured by Japan Food Processing) 30
100 parts by weight of 1 part by weight and 1 part by weight of magnesium stearate (manufactured by Taihei Chemical Industry) are mixed in a plastic bag, and one tablet is used using a small rotary tableting machine (Clean Press Collect 18K: manufactured by Kikusui Seisakusho). Each tablet was formed into a tablet (uncoated tablet) having a weight of 250 mg, a diameter of 8.5 mm, and a thickness of 4.3 mm.

Example 1 The components shown in Table 1 below were mixed,
Dissolve the composition in water to a weight concentration of 10%,
20 mg per tablet (8 weight ratio based on uncoated tablet)
%) (Aqua coater A
After coating with QC-48T (manufactured by Freund), it was blown dry to obtain a coated tablet.

[0033]

[Table 1] Xanthan gum (Echo gum SF: Kelco) 15 parts by weight Pullulan (Hayashibara Shoji) 15 parts by weight Mannitol (D-mannitol: Kao) 70 parts by weight ───────────── ───────────────── Total 100 parts by weight

Example 2 The components shown in Table 2 below were mixed,
Dissolve the composition in water to a weight concentration of 10%,
20 mg per tablet (8 weight ratio based on uncoated tablet)
%) (Aqua coater A
After coating with QC-48T (manufactured by Freund), it was blown dry to obtain a coated tablet.

[0035]

[Table 2] Gellan gum (manufactured by Monsanto) 15 parts by weight Pullulan (manufactured by Hayashibara) 15 parts by weight Mannitol (D-mannitol: manufactured by Kao) 70 parts by weight ──────────────── ────────────── Total 100 parts by weight

Example 3 The components shown in Table 3 below were mixed,
Dissolve the composition in water to a weight concentration of 35%,
20 mg per tablet (8 weight ratio based on uncoated tablet)
%) And the pan coating machine (NO-16-
D: manufactured by Kikusui Seisakusho Co., Ltd.) and then blown dry to obtain coated tablets.

[0037]

[Table 3] Gellan gum (Monsanto) 5 parts by weight Pullulan (Hayashibara Shoji) 6 parts by weight Mannitol (D-mannitol: Kao) 89 parts by weight ──────────────── ────────────── Total 100 parts by weight

Example 4 The components shown in Table 4 below were mixed,
The composition is dissolved and dispersed in water so as to have a weight concentration of 10%, and the above uncoated tablet is coated with a coating apparatus (Aqua Coater AQC-48T: Freund: 8 mg / weight ratio of 20% per tablet). Co., Ltd.) and dried by blowing air to obtain coated tablets.

[0039]

[Table 4] Xanthan gum (Echo gum SF: manufactured by Kelco) 15 parts by weight Pullulan (manufactured by Hayashibara) 15 parts by weight Mannitol (D-mannitol: manufactured by Kao) 50 parts by weight Titanium oxide (Ishihara Sangyo) 20 parts by weight ────────────────────────── Total 100 parts by weight

Comparative Example 1 : In the case where a general coating composition was used --- The components shown in Table 5 below were mixed, and the composition was subjected to a weight concentration of 1
It is dissolved and dispersed in water so as to be 0% to form a coating solution, and a coating device (Aqua Coater AQC-48T: manufactured by Freund Corporation) so that the above uncoated tablet has a weight of 20 mg per tablet (8% by weight based on the uncoated tablet). , And dried by blowing air to obtain a coated tablet.

[0041]

[Table 5] HPMC (TC-5R: manufactured by Shin-Etsu Chemical) 70 parts by weight Titanium oxide (titanium oxide: Ishihara Sangyo) 20 parts by weight Macrogol 6000 (Macrogol 6000: manufactured by NOF Corporation) 10 parts by weight ────── ───────────────────────────── Total 100 parts by weight

Comparative Example 2 : In the case where only the gelling agent was used as the coating composition --- The composition shown in Table 6 below was dissolved in water so as to have a weight concentration of 1%, and the above uncoated tablets were 20 mg per tablet. Coating was attempted with a coating device (Aqua Coater AQC-48T: manufactured by Freund) so that the weight ratio was 8% based on the uncoated tablet, but the coating layer was peeled off and coating was impossible.

[0043]

[Table 6] Xanthan gum (Echo gum SF: manufactured by Kelco) 100 parts by weight 計 Total 100 parts by weight

Comparative Example 3 : In the case where a composition containing only a gelling agent and a binder was used as a coating composition --- The composition shown in Table 7 below was dissolved in water so as to have a weight concentration of 2%, Coating was attempted on a tablet with a coating device (Aqua Coater AQC-48T: manufactured by Freund) so that the weight per tablet became 20 mg (weight ratio to the uncoated tablet: 8%), but the coating time was 5 times longer than that of Comparative Example 1. Utility was extremely bad.

[0045]

[Table 7] Xanthan gum (Echo gum SF: 50 parts by weight manufactured by Kelco) Pullulan (manufactured by Hayashibara Shoji) 50 parts by weight 部──── Total 100 parts by weight

Comparative Example 4 : In the case where a composition having an appropriate amount of a gelling agent, a large amount of a binder, and a small amount of a sugar alcohol was used as a coating composition--the composition shown in Table 8 below was used at a concentration of 10% by weight. And dissolved in water so as to give 20 mg per tablet (8% by weight based on the uncoated tablet) with a coating device (Aqua Coater AQC-48T: manufactured by Freund) and then blown dry. To obtain coated tablets.

[0047]

[Table 8] Xanthan gum (Echo gum SF: manufactured by Kelco) 20 parts by weight Pullulan (manufactured by Hayashibara Shoji) 50 parts by weight Mannitol (D-mannitol: manufactured by Kao) 30 parts by weight ───────────────── Total 100 parts by weight

Test Method 1 : The coated tablets of Examples 1, 2, 3 and 4 and the coated tablets of Comparative Examples 1 and 4 which could be produced were slimy and sticky (sticky) by five skilled panelists. ) And a sensory test of slipperiness were performed. Table 9 shows the results. Slimy feeling,
Regarding the stickiness and the slipperiness, the degree of the touch, such as the presence or absence of each touch when each tablet was contained in the oral cavity, was used as a criterion.

[0049]

[Table 9]

Degree of feel: not felt <somewhat
<Yes <Strong

The coated tablets of Examples 1, 2, 3 and 4 all had a reduced sliminess and stickiness.
In addition, there was a slippery feeling, and all of them showed good taking characteristics.

On the other hand, the coated tablet of Comparative Example 1 had an unfavorable result that it had a strong slimy feeling, had a sticky feeling, and did not feel slippery. The coated tablet of Comparative Example 4 was different from the coated tablet of Comparative Example 1. Although the sticky feeling was suppressed, the slimy feeling was not eliminated.

Test Method 2 : Each tablet was immersed in water for 1 second, and then placed on a stainless steel plate at an angle of 30 °, and the sliding distance of the tablet was examined. The maximum travel distance when falling down is 8
cm, and the tablets that have slid so far are regarded as tablets having good slippage (marked as “○” in Table 10), and the tablets that did not slip to the maximum movement distance are tablets with poor slippage (marked as “x” in Table 10). Was considered. This test was performed three times, and the results are shown in Table 1.
0 is shown.

[0054]

[Table 10]

：: Tablet with good sliding, ×: Tablet with poor sliding, (): Actual measured value of moving distance

The coated tablets of Examples 1, 2, 3 and 4 all slid to the maximum travel distance and were very slippery.
The coated tablet of Comparative Example 4 also slid to the maximum moving distance, but was slightly harder to slip than the coated tablets of Examples 1, 2, 3 and 4 from the observation of the sliding manner. On the other hand, Comparative Example 1
The coated tablet did not almost slip on the stainless steel plate.

[0057]

As described above, by coating the composition for easy-to-consume coating of the present invention on a solid substance, slimy feeling and sticking feeling (or sticky feeling) in the oral cavity at the time of ingestion are suppressed, A solid preparation that is slippery and easy to take for children, the elderly, patients with reduced swallowing function, and the like can be obtained.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C076 AA44 AA45 BB01 DD67T EE30L EE30P EE32L FF25 FF31 FF35 FF70 GG16

Claims (13)

[Claims] 1. An easy-to-wear coating composition comprising the following component compositions a), b) and c), based on 100 parts by weight of the total amount of the coating layer in the coating layer, a) 5 to 25 weight parts of a gelling agent Parts) b) 5 to 25 parts by weight of binder; c) 40 to 90 parts by weight of sugar alcohol. 2. The composition for easy-to-wear coating according to claim 1, wherein the gelling agent is selected from one or more selected from the group consisting of xanthan gum, tamarind gum, carrageenan, locust bean gum, gellan gum and agar. . 3. The composition for easy-wearing coating according to claim 1, wherein the binder is one or more selected from the group consisting of pullulan, hydroxypropylmethylcellulose, hydroxypropylcellulose and methylcellulose. 4. The composition for easy-coating coating according to claim 1, wherein the sugar alcohol is selected from one or more selected from the group consisting of mannitol, erythritol, xylitol and sorbitol. . 5. The composition according to claim 1, further comprising one or more selected from the group consisting of a lubricant, a colorant, a plasticizer, a surfactant, a sweetener, a flavor, a odorant, and a fragrance. The composition for easy-to-take coating according to any one of the above. 6. A solid preparation coated with the composition for easy-to-take coating according to any one of claims 1 to 5. 7. The solid preparation according to claim 6, which is a tablet or a pill. 8. A solid preparation, wherein the precoated solid is further coated with the composition for easy-to-wear coating according to any one of claims 1 to 5. 9. The solid preparation according to claim 8, wherein the precoating is for controlling the enteric release. 10. The composition according to claim 6, further comprising a drug.
10. The solid preparation according to any one of 9. 11. The solid weight to be coated is 100.
The solid preparation according to any one of claims 6 to 10, wherein the weight of the coating layer is 0.5 to 50 parts by weight based on part by weight. 12. The solid preparation according to any one of claims 6 to 11, wherein the surface of the coating layer is slippery when taken. 13. Assuming that the total amount of the coating layer is 100 parts by weight, a) 5 to 25 parts by weight of a gelling agent, and b) 5 to 5 parts of a binder
A composition comprising 25 parts by weight and c) 40 to 90 parts by weight of a sugar alcohol is coated with a solid weight of 100 to be coated.
A coating solution was prepared by dissolving in water alone or a mixed solvent of water and alcohol so as to have a weight concentration of 3 to 50% by weight based on parts by weight, and a non-pre-coated solid or a pre-coated solid was coated with this coating liquid. And then drying.