KR100855189B1 - Oral Disintegrating tablets - Google Patents

Abstract

The present invention relates to orally disintegrating tablets, and more particularly, containing loratadine or desloratadine as pharmaceutically effective active ingredients, using water-soluble carbohydrates as excipients, spray-dried starch and spray drying as disintegrating agents. By using the mixed lactose, the tablet prepared as it disintegrates rapidly in the oral cavity to promote the absorption of the active ingredient in vivo, so that the expression of the drug is fast, and there is little residue in the oral cavity when taking it, so there is little residue and foreign body feeling. The present invention relates to an improved oral quick disintegrating tablet which can be mass-produced at low cost since the fast disintegrating tablet has a hardness that is easily disintegrated in the oral cavity and has a hardness of more than easy handling.

Oral fast disintegrating tablets, loratadine, desloratadine, excipients, disintegrant, residual, foreign body

Description

Oral disintegrating tablets

The present invention relates to an orally disintegrating tablet, comprising an antihistamine such as loratadine or desloratadine as an active ingredient and a pharmaceutically active ingredient requiring rapid disintegration, using a water-soluble carbohydrate as an excipient, and spray drying as a disintegrant. A tablet consisting of a composition using a mixture of starch and spray-dried lactose, which rapidly disintegrates in the oral cavity, has little residual and foreign body feeling in the oral cavity when taken, and has a hardness of at least a level that is easy to handle after formulation. It can be produced simply using the production equipment of the general solid preparation.

In general, tablets and capsules, which make up most of the oral preparations, are not easy to take in the elderly or children who are difficult to swallow the medicine, and in the case of other powders and granules, they may easily remain in the mouth after administration, causing discomfort. Dosing the correct dose is difficult.

On the other hand, fast disintegrating tablets disintegrate rapidly in the mouth, the drug is expressed quickly and can be easily taken at rest, so it can be said that the formulation is most suitable for the improvement and treatment of allergy symptoms.

Several drugs that dissolve or disintegrate in such oral cavity are known as fast disintegrating tablets.

For example, Japanese Patent Laid-Open No. 62-50445 describes a matrix-type fast disintegrating preparation after preparing an aqueous solution containing gelatin together with a pharmaceutically acceptable active ingredient and lyophilizing it.

However, the manufacturing method according to the patent publication is difficult to manufacture by using the manufacturing equipment of the conventional solid preparation, and thus the investment of the equipment must follow, there is a disadvantage that takes much time compared to the general solid preparation in actual production However, despite the fast disintegration time (within 10 seconds) of the finished formulation, it is not widely used.

On the other hand, Japanese Patent Laid-Open No. H2-32014 also describes the fast disintegrating tablet in the oral cavity prepared by freeze-drying the sugar, but as in the above technique, it did not solve the problem of equipment for manufacturing and freeze-drying the mold. Mass production is difficult, and due to the nature of the manufacturing method, the hardness of the formulation is low, there is a difficulty in normal packaging (PTP) or handling.

U. S. Patent No. 3,885, 026 discloses a method for preparing porous tablets by mixing volatile excipients such as urea, urethane, ammonium carbonate, naphthalene and the like with other tablet components, followed by tableting and heating to volatilize the volatile excipients. However, the disadvantage is that excipients remaining in these tablets can cause fatal harm to the patient.

Meanwhile, examples of commercially available fast disintegrating preparations include products such as Zofran zydis (ondansetron preparation, Glaxowelcome) and Claritin RediTab (loratadine preparation, Schering).

The above product has the advantage of quickly dissolving in the oral cavity within 2 to 3 seconds, but after injecting the drug solution into the pre-molded container, and freeze-dried under special temperature conditions, it is difficult to mass production due to low productivity during manufacture, Even after manufacturing, it is required to be packed with a special material, and thus has a disadvantage of low economical efficiency due to high production cost.

In addition, as a commercially available formulation, Zomig Rapimelt (zolmitriptan formulation, AstraZeneca) is a tablet formulation containing an effervescent substance, but it does not have satisfactory oral disintegration and also has a disadvantage of poor medication due to generation of oral foaming gas. have.

The above-described prior art and products manufactured and distributed using the same do not have a mechanical strength that is easy to handle, and have a common manufacturing method, which requires complicated investment and expensive packaging and production equipment investment. Has disadvantages

Therefore, the inventors of the present invention, as a pharmaceutically acceptable active ingredient, antihistamine, which is a pharmaceutical ingredient requiring rapid expression, shows rotatadine or desloratadine as an active ingredient, shows fast disintegration, and a feeling of retention when taking Efforts have been made to achieve the above-mentioned problems, such as the satisfaction of normal handleable hardness.

As a result, it was found that the above-mentioned problems can be solved by selecting and using a specific excipient having water solubility, and mixing starch and lactose, particularly spray-dried, as a disintegrating agent, thereby completing the present invention.

Tablets made of the composition of the present invention has a disintegration rate, such as the disintegration rate of sokbung tablets manufactured and distributed by conventional lyophilization method, so that the disintegration is excellent, especially the active ingredient requiring fast expression of the drug such as histamine as an active ingredient Useful when used.

In addition, tablets made of the composition of the present invention is good in taking less oral residue and foreign body feeling.

In addition, the composition proposed by the present invention can also be easily produced as a production equipment of the general solid preparation is advantageous in terms of cost reduction, it is possible to manufacture a tablet that maintains the hardness that can be handled in normal.

Accordingly, an object of the present invention is to provide a novel oral fast disintegrating tablet comprising loratadine or desloratadine as an antihistamine as an active ingredient.

The present invention relates to a fast disintegrating tablet containing loratadine or desloratadine with pharmaceutically effective antihistamine activity, comprising: a water-soluble carbohydrate as excipient, a spray-dried starch as a disintegrant and a mixture of spray-dried lactose, a disintegration aid and a pharmaceutical Orally quick disintegrating tablets comprising a generally acceptable additive.

Hereinafter, the present invention will be described in detail.

The present invention comprises loratadine or desloratadine as a pharmaceutically effective active ingredient, water-soluble carbohydrates as excipients, and spray-dried starch and spray-dried lactose as a disintegrant, thereby mixing It disintegrates rapidly in the oral cavity and can promote the absorption of the active ingredient in vivo, so the expression of the drug is fast.There is little residue in the oral cavity when taking it, and there is no foreign body feeling. It is directed to an improved fast disintegrating tablet which can be easily prepared by using fast dispersing tablets in the production of general solid preparations.

Hereinafter will be described in detail for each component constituting the fast disintegrating tablet of the present invention.

As a pharmaceutically effective fast-acting active ingredient used in the fast disintegrating tablet of the present invention, loratadine, desloratadine, or a combination thereof was used as an antihistamine requiring fast expression of the drug and effective improvement of allergy symptoms. In addition, cetirizine, fexofenadine, etc., which have a similar mechanism of action and are capable of being absorbed by rapid disintegration of the preparation in the oral mucosa or the gastrointestinal tract, may be used.

Such active ingredients are preferably contained in an amount of 1 to 30% by weight in the total weight of the tablet composition, the content varies depending on the amount of the active ingredient is used to show the pharmacological activity.

The fast disintegrating tablets of the present invention, in addition to the pharmaceutically effective active ingredients described above, contain a proportion of a mixture of water-soluble carbohydrates as excipients, starch spray dried as a disintegrant and spray dried lactose, disintegrating aids and pharmaceutically acceptable additives. Include.

The fast disintegrating tablet of the present invention is optionally used as an excipient as a water-soluble excipient that can be dissolved by saliva among the excipients generally used in solid preparations. The excipients are not limited in kind and particle size unless granulated separately.

As such excipients, water-soluble carbohydrates are used. Specifically, sugar alcohols having 4 to 12 carbon atoms, sugars including monosaccharides and disaccharides, and water-soluble carbohydrates selected from starch hydrolysates may be used. More specifically, the excipients include mannitol, sorbitol, xylitol, erythritol, maltitol and lactitol as sugar alcohols, glucose, maltose, dextrose, sucrose, fructose, trehalose, sucralose and polydextrose as sugars. As the starch hydrolyzate, one or a mixture of two or more selected from dextrin, maltodextrin and the like can be used. The water-soluble carbohydrate used in the above-mentioned selection exhibits proper disintegration regardless of its kind.

At this time, the excipient is used in the range of 20 to 50% by weight, preferably 30 to 50% by weight of the total weight of the tablet composition, when the amount of the excipient exceeds 50% by weight, the resulting tablet is cured to delay the disintegration rate. When the amount of excipient used is less than 20% by weight, the disintegration time is not significantly delayed, but the components other than the excipient are relatively increased, and in particular, the proportion of starch which is insoluble in water increases, which increases the residual feeling in the mouth after disintegration. Show a tendency.

The fast disintegrating tablets of the present invention use a proportion of a mixture of spray dried starch and spray dried lactose as disintegrants. As the disintegrant, it is possible to directly tablet among disintegrants generally used in solid preparations in the art, and used a disintegrant having hygroscopicity. In the present invention, the starch is selected to satisfy these characteristics, and the starch having a porous structure is spray-dried in order to rapidly disintegrate when the water is taken together with water to be made faster.

On the other hand, the spray-dried starch selected as the disintegrant and the excipient alone can obtain a tablet that disintegrates within a short enough time, but does not completely remove the residual feeling in the oral cavity caused by the excipient or the disintegrant remaining in the oral cavity when taken. There is a problem.

Thus, in the present invention, there is one feature in the technical configuration of mixing spray dried starch and spray dried lactose as a disintegrating agent to solve the residual feeling. That is, the lactose is a material having a moderate water solubility between the water-soluble carbohydrate used as an excipient and the dry powder starch selected as a disintegrant, in the present invention spray-dried to increase the moisture penetration of the lactose more porous Spray dried lactose having the structure of was selected and used.

In addition, in order to quickly disintegrate in the oral cavity, the mixing ratio of spray dried starch and spray dried lactose, which is used as a disintegrant, was adjusted. That is, when the spray-dried starch and the spray-dried lactose are used in a ratio of 2: 8 to 4: 6 by weight, the disintegration time in the oral cavity is shortened. At this time, when the ratio of starch is excessively increased beyond the above range, the residual and foreign body feeling in the oral cavity is increased due to the water insolubility of starch, and on the contrary, when the ratio of lactose is excessively high beyond the above range, stickiness during oral disintegration process is observed. Occasionally, the dosage is not good, and the overall disintegration time tends to be delayed.

At this time, the disintegrant mixture is used in the range of 30 to 70% by weight, preferably 40 to 60% by weight of the total weight of the tablet composition, when the amount of disintegrant exceeds 70% by weight tends to increase the residual feeling When the amount of disintegrant is less than 30% by weight, the disintegration rate in the oral cavity tends to be slow.

On the other hand, the use ratio of the excipient and the disintegrant is also important, but in the present invention, the use ratio of the excipient and the disintegrant is adjusted to a weight ratio of 1: 1 to 2, preferably 1: 1, so that the retention of oral cavity and tablets Good for quick disintegration.

The disintegration adjuvant may generally use a pharmaceutically acceptable disintegration adjuvant in the art, specifically, for example, starch sodium glyconate, crospovidone, croscarmellose sodium, carboxymethylcellulose calcium, pregelatinized starch And one or a mixture of two or more selected from ion exchange resins and the like. At this time, the disintegration aid may use 1 to 5% by weight of the total weight of the tablet composition, if the amount of the disintegration aid exceeds the above range, after disintegration in the oral cavity, there is a tendency to increase the residual feeling.

The fast disintegrating tablet of the present invention may use pharmaceutically acceptable additives in the art, in addition to the above components, by the choice of those skilled in the art. Such pharmaceutically acceptable additives are not particularly limited, but specifically, one or two or more mixtures selected from sweeteners, lubricants, acids and alkalizing agents, foaming agents, microporous agents, and the like may be used. It is preferred to use in the range of 5 to 20% by weight of the total weight of the composition.

As such additives, representatively, the sweetening agent may be selected from aspartame, stevioside, saccharin, sucrose, altam, acesulfame potassium and sucralose phosphorus, and the lubricant is a colloidal silicon dioxide Examples of acids and alkalizers include organic acids such as ascorbic acid, citric acid, succinic acid, tartaric acid, malic acid, sodium phosphate, potassium phosphate, sodium hydroxide, hydroxide, and talc, magnesium stearate and sodium stearyl fumarate, stearic acid, and glyceryl behenate. As the blowing agent such as potassium and ammonium hydroxide, one or a mixture of two or more selected from light silicic anhydride, povidone, magnesium metasilicate and the like can be used as the fine pore forming agent such as sodium hydrogen carbonate, sodium carbonate, calcium carbonate and the like. It is not obvious.

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

Example 1

As a active ingredient, loratadine was apologies in a 40 mesh sieve, and mannitol as an excipient, spray dried starch as a disintegrant, and spray dried lactose were added to a V-type mixer and mixed for 10 minutes. Stevioside was mixed as a sweetener to this mixture, sodium starch glyconate was added as a disintegration aid, and then added to a V-type mixer and mixed for 3 minutes. To this mixture, colloidal silicon dioxide was added for the purpose of lubrication, and magnesium stearate was added again to a V-type mixer and finally mixed. At this time, the composition components and the amount used are shown in Table 1 below.

The mixture was compressed into tablets under a pressure of 3.0 to 6.0 kN, a thickness of 3.0 to 4.0 mm, and a rotation speed of 30 rpm using a rotary tableting machine (MRC-33, Sejong) to prepare fast disintegrating tablets. The hardness was maintained at 4-5 kp to allow for packaging.

Examples 2-9 and Comparative Examples 1-4

Fast disintegrating tablets were prepared under the same conditions as in Example 1, wherein the composition components and the amount used were as shown in Table 1 below.

However, instead of mannitol of Example 1, sorbitol (Example 5), maltose (Example 6), dextrose (Example 7) and fructose (Example 8), and desloratadine (Example 9) as active ingredients There is a difference in what was used.

Experimental Example 1

The tablets prepared according to Examples 1 to 9 and Comparative Examples 1 to 4 were used to measure the disintegration time in the mouth and the residual feeling when taking the medicine by the method shown below, and the results are shown in Table 3 below.

1) Intraoral disintegration time: The time until complete disintegration of tablets in the oral cavity was measured in 10 adult men, and the test was repeated three times to indicate an average value.

2) Residual feeling: The degree of residual feeling was measured according to the following Table 2 until 10 tablets were completely removed from the oral cavity in 10 adult men.

Precision Residual A There is hardly any residual feeling or other foreign matter. B There is some residual light, but it disappears within 60 seconds. C A feeling of residual that does not disappear within 60 seconds is felt. D Induces discomfort due to residual feeling that does not disappear within 60 seconds E Disintegration does not occur within 60 seconds.

division Hardness (kp) Disintegration time (sec) Residual Example 1 4.0 40-50 B Example 2 4.2 40 to 45 B Example 3 4.2 30 to 35 A Example 4 4.2 40-50 B Example 5 5.0 40 to 45 A Example 6 4.6 35 to 45 A Example 7 4.6 35 to 45 A Example 8 4.5 40 to 45 A Example 9 4.1 30 to 35 A Comparative Example 1 4.0 50 to 60 D Comparative Example 2 6.0 More than 120 E Comparative Example 3 4.1 60 to 70 C Comparative Example 4 4.2 80 to 90 D

As shown in Table 3 above, in Comparative Example 1, the residual feeling and stickiness caused by starch and lactose after the disintegration in the oral cavity were severe, causing unpleasantness of the tester, and in the case of Comparative Example 2, curing of the tablet occurred at the same tableting pressure. The time was greatly delayed and a feeling of crystallinity was felt.

In the case of Comparative Example 4, the residual feeling was felt after disintegration in the oral cavity, and Comparative Example 3 felt an unpleasant stickiness during the disintegration process after invasion due to lactose.

As described above, the tablets presented by the present invention can easily prepare tablets having mechanical strength (4 to 5 kp) without difficulty in normal handling and distribution by using existing production facilities of general solid preparations. In addition, since the tablet prepared by the composition disintegrates rapidly in the oral cavity, it can promote the absorption of the active ingredient in vivo, so that the expression of the drug can be expressed quickly. This shows a reduced effect.

Claims (18)

In the fast disintegrating tablet containing loratadine or desloratadine as an active ingredient having pharmaceutically effective antihistamine activity, At least one water-soluble carbohydrate selected from sugar alcohols having 4 to 12 carbon atoms as an excipient, sugars including monosaccharides and disaccharides, and at least one starch hydrolyzate selected from dextrin and maltodextrin; A mixture of spray dried starch and spray dried lactose as a disintegrant in a ratio of 2: 8 to 4: 6 by weight; Disintegration aids; And Oral fast disintegrating tablet, characterized in that prepared by mixing, tableting and pharmaceutically acceptable additives. The tablet according to claim 1, wherein the active ingredient comprises 1 to 30% by weight of the total weight of the composition. delete According to claim 1, wherein the sugar alcohol is at least one selected from mannitol, sorbitol, xylitol, erythritol, maltitol and lactitol; The sugars include glucose, maltose, dextrose, white sugar, fructose, trehalose, sucralose and polydextrose; A starch hydrolyzate, characterized in that at least one selected from dextrin and maltodextrin. The tablet of claim 1, wherein the excipient comprises 20-50 wt% of the total weight of the composition. The tablet of claim 1, wherein the disintegrant is 30 to 70% by weight of the weight of the composition. delete The tablet according to claim 1, wherein the excipient and the disintegrant are included in a weight ratio of 1: 1 to 2. The tablet of claim 1, wherein the disintegration aid is at least one selected from sodium starch glyconate, crospovidone, croscarmellose sodium, calcium carboxymethyl cellulose, pregelatinized starch and ion exchange resin. The tablet of claim 1, wherein the disintegration aid is included in an amount of 1 to 5% by weight based on the total weight of the composition. The tablet according to claim 1, wherein the pharmaceutically acceptable additive is at least one selected from sweeteners, glidants, acids and alkalizing agents, foaming agents and micropore formers. The tablet according to claim 1, wherein the pharmaceutically acceptable additive is contained in an amount of 5 to 20% by weight of the composition. 12. The tablet according to claim 11, wherein the sweetener is at least one selected from aspartame, stevioside, saccharin, sucrose, altam, acesulfame potassium and sucralose. The tablet according to claim 11, wherein the lubricant is at least one selected from colloidal silicon dioxide, talc, magnesium stearate and sodium stearyl fumarate, stearic acid, glyceryl behenate and magnesium metasilicate aluminate. The method of claim 11, wherein the acid and alkalizing agent is citric acid, succinic acid, tartaric acid, acetic acid, phosphoric acid, malic acid, lactic acid, potassium phosphate, sodium phosphate, sodium hydroxide, potassium hydroxide, ammonium acetate, ammonium hydroxide, triethylamine, triethanolamine Tablets, characterized in that at least one selected from potassium citrate and sodium citrate. 12. The tablet according to claim 11, wherein the blowing agent is at least one mixture selected from sodium carbonate, sodium bicarbonate and potassium hydrogen carbonate. 12. The tablet according to claim 11, wherein the microporous agent is at least one mixture selected from hard silicic anhydride, povidone and magnesium metasilicate aluminate. delete