KR101216301B1 - Method for preparing rapidly disintegrating formulation for oral administration and medicine packing machine for the same - Google Patents

Abstract

The present invention relates to a method for preparing oral administration fast-acting preparations, and to a pharmaceutical packaging device for preparing the same, characterized in that the packing is filled with a mixed powder comprising a pharmaceutically active ingredient and sugars or sugar alcohols, and then the filling is heated. According to the present invention, it is possible to easily and economically prepare an oral dosage form for oral administration which has high drug compliance and rapidly dissolves in the oral cavity.

Rapid preparations, heating, manufacturing, packaging

Description

METHOD FOR PREPARING RAPIDLY DISINTEGRATING FORMULATION FOR ORAL ADMINISTRATION AND MEDICINE PACKING MACHINE FOR THE SAME}

The present invention relates to a method for preparing oral administration preparations using melt bonding, a pharmaceutical packaging device for the preparation thereof, and a rapid preparation which is rapidly dissolved in the oral cavity produced thereby.

In general, a method of preparing a fast-solving tablet includes a lyophilization method, a method using a disintegrant or a sublimable substance, a method by humidification and dehumidification, and the like.

Representative examples of fast-acting tablet formulations known to date are those prepared by lyophilizing a solution containing a drug (US Pat. Nos. 5,631,023 and 5,976,577 to RP Scherer). formulations are Pepsi de ^® Al PD (Pepcid ^® RPD) (famotidine preparations, Merck), Morozov is ^® Xi disk (Zofran ^® zydis) (ondansetron preparation, Glaxo Wellcome), Claritin ^® Ready Taps (Claritin ^® RediTabs) Products such as; These products have the advantage of quickly dissolving in the oral cavity within 2 to 3 seconds, but have low productivity, such as the need to freeze-dry them under special temperature conditions after injecting the drug solution into preformed containers. The necessity of packaging increases the cost of production.

Instead of the lyophilization method having such disadvantages, Yamanouchi, Japan, has developed the WOWTAB technology. In the related patent document WO 99/47126, a water-soluble polymer is used as a binder. And a method of preparing a fast solvent containing no residual organic solvent by compressing the same with a high-humidity condition and then drying it, and WO 93/12769 discloses a suspension of an active ingredient, agar, sugar, and the like. To a mold and dried at -760mmHg at 30 ℃ discloses a method for removing moisture. However, these methods have the disadvantage of low productivity and difficulty in maintaining quality uniformity between products.

As another method of manufacturing fast-acting tablets, Cima Labs developed Orasolv technology, which is described in US Patent Nos. 5,178,878 and 6,024,981. As the representative product formulated using this technique there is a Jimmy that ^® Rafi melt (Zimig ^® Rapimelt) (jolmi trip Zeneca burnt agents, Astra), the product is a tablet formulation containing a foaming material have an oral disintegrant degradable satisfactory Not only that, there is a disadvantage in that the medication is poor due to the generation of foam gas in the oral cavity.

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

In addition, US Pat. No. 4,134,943 discloses a solvent having a freezing point in the range of -30 to 25 ° C, such as water, cyclohexane, benzene, tert-butanol, etc., to the remaining purification components, and then cooling the mixture to below freezing point. Disclosed is a method of preparing a porous tablet by solidifying the solvent followed by tableting and evaporating the solvent. However, this method has the disadvantage of low productivity and very high toxicity of the organic solvent used.

As can be seen from the above, conventional methods for preparing fast-acting preparations are prepared by preparing a formulation containing a specific component that can be removed by a method such as sublimation, volatilization, dehumidification, and the like. It is based on the removal of the method to form a pore by the removal of its components, so that saliva and the like can rapidly penetrate into such a passage when taken. However, according to this conventional method, there is a fear that the physical properties of the preparation are significantly lowered or the properties are severely changed while a passage which is not present in the initial preparation is forcibly made.

Therefore, there is an urgent need to develop a method for preparing a fast-acting preparation that can be easily produced and easily taken without causing problems due to such existing methods.

Accordingly, it is an object of the present invention to provide a method and a pharmaceutical packaging device for manufacturing the same, which can easily and economically prepare a fast-acting formulation which has high drug compliance and is rapidly dissolved in the oral cavity.

The above objects and various advantages of the present invention will become more apparent from the preferred embodiments of the invention described below with reference to the accompanying drawings by those skilled in the art.

In the present invention to achieve the above object,

(A) filling the packaging with a mixed powder comprising the pharmaceutically active ingredient and sugars or sugar alcohols; And

(B) heating the filler obtained in step (A);

It provides a method for producing a rapid-release formulation for oral administration comprising a.

In addition, the present invention provides a rapid preparation for oral administration prepared by the above production method.

Furthermore, in the present invention,

Molded film supply unit for supplying a molded film;

A film molding part for molding the molded film to produce a lower pocket film having a container-shaped pocket;

A medicine injecting unit for filling and injecting a mixed powder or a shaped tablet by pressing the mixed powder into the pocket of the lower pocket film;

A heater unit for heating and melting bonding the filling material in the molding pocket film;

A sealing part attaching an upper cover film to the lower pocket film;

Cutting portion for cutting the packaging material of the lower pocket film and the upper cover film attached in a predetermined unit; And

A control unit for operation control;

It provides a pharmaceutical packaging device for the manufacture of a rapid-release formulation for oral administration comprising a.

Hereinafter, the present invention will be described in more detail.

The method according to the present invention, unlike the conventional method of forcibly creating a passage through sublimation, volatilization, dehumidification, etc., is filled with a mixed powder of a pharmaceutically active ingredient having a large number of passages and sugars or sugar alcohols (step (A )) And by heating (step (B)) by melting bonding to maintain the existing passage as it is.

Such a method of the present invention is not only an excellent method without deterioration of the properties and physical properties of the formulation by forcible passage formation, but also a simple and economical method consisting of a series of mixing / filling / heating processes.

Step (A)

Compositions (mixed powders) used in the preparation of the preparations in the present invention include pharmaceutically active ingredients and sugars or sugar alcohols, in addition to these may further comprise pharmaceutically acceptable additives.

Hereinafter, the components of the composition used in the present invention will be described in detail.

(1) pharmaceutically active ingredients

① antipyretic, analgesic or anti-inflammatory

For example, tramadol, ibuprofen, dexibuprofen, aspirin, acetaminophen, indomethacin, diclofenac sodium, ketoprofen, isopropyl antipyrine, phenacetin, fluorobiprofen, phenylbutazone, etodollac, selecock Sieve, etoricoxib, and pharmaceutically acceptable salts thereof.

② anti-gastric ulcer

For example, cimetidine, pamotidine, ranitidine, nizatidine, loxatidine and pharmaceutically acceptable salts thereof.

③ cardiovascular or vasodilator

Examples include nifedipine, amlodipine, verapamil, captopril, diltiazem hydrochloride, propranolol, oxprenol, nitroglycerin, enalapril and pharmaceutically acceptable salts thereof.

④ antibiotics

For example, ampicillin, amoxicillin, cephalexin, cefuroxime, ceftinir, cepadroxil, ceftprozil, cefpodoxim, ceftudirene, sefacller, seppicsim, cepradine, loraka bep, cefti Butenes, cepatrizine, cefefen, erythromycins, tetracyclines, quinolones, and pharmaceutically acceptable salts thereof.

⑤ antitussives or asthma treatment

For example, theophylline, aminopyrin, codeine phosphate, methylephedrine hydrochloride, dextromethorphan, noscarpine, salbutamol, ambroxol, glenbuterol, terbutalin, montelukast and pharmaceutically acceptable salts thereof There is this.

⑥ Antiseptic or gastric function regulator

For example, ondansetron, metoclopramide, domperidone, trimebuterine maleic acid, cisapride, levosulfide and pharmaceutically acceptable salts thereof.

⑦ Erectile Dysfunction Treatment

Drugs that block the degradation of nitric oxide include, for example, sildenafil, vardenafil, tadalafil, udenafil and pharmaceutically acceptable salts thereof.

⑧ Dementia Treatment

For example, donepezil, galantamine, rivastigmine, acetyl carnitine, memantine, zaliproden and pharmaceutically acceptable salts thereof.

In addition to prostatic hyperplasia such as tamsulosin; Migraine medications such as sumatriptan, zolmitriptan, lizatriptan; Mental stimulant; Antimicrobial agents; Antihistamines such as loratadine and fexofenadine; Oral diabetic agents such as glimepiride; Allergic agents; Birth control pills; Vitamins; Anticoagulants; Muscle relaxants; Brain metabolism improvers; Diuretics such as torsemide, furosemide; Antiepileptic drugs such as gabapentin, pregabalin, valproic acid, topiramate, carbamazepine, lamotrigine, oxcabazepine; Parkinson's disease drugs such as selegiline; Antipsychotics such as risperidone, ziprasidone, quetiapine, olanzapine, clozapine, paliperidone, and pharmaceutically acceptable salts thereof may also be used. It is also applicable to biological agents such as oral vaccines.

The active ingredient may be used in an amount of 0.01 to 90% by weight, preferably 0.02 to 70% by weight relative to the total weight of the mixed powder.

(2) sugars or sugar alcohols

Sugars or sugar alcohols maintain their shape and determine the rate of dissolution during preparation of the formulation. In the oral cavity, sugars or sugar alcohols are important components that affect sweetness, solubility, and touch, and should have good sweetness and water solubility. Sugars and sugar alcohols that can be used include lactose, glucose, sucrose, fructose, mannitol, sorbitol, xylitol, erythritol, rebulose, maltitol, maltose, maltodextrin, paratinose, trehalose, dextrose and their Mixtures, and the like, but are not limited thereto.

The sugar or sugar alcohols may be used in an amount of 10 to 99.9% by weight, preferably 20 to 95% by weight based on the total weight of the mixed powder. If the content of the sugar is less than 10% by weight, there is a problem in that the sweetness and the mouth feel are poor.

(3) pharmaceutically acceptable additives

In the present invention, optionally one or more pharmaceutically acceptable additives may be used in addition to the pharmaceutically active ingredient and sugars or sugar alcohols for the purpose of improving the flowability, ease of taking and physical properties of the mixture prior to filling. Examples of pharmaceutically acceptable additives include low melting point binders, disintegrants, glidants, excipients (eg sweeteners, fillers) and the like.

The low-melting binder component is used to help maintain the shape of the product when handling and storing the product as a component that assists in the rigidity of the fast-acting preparation. As the low melting point binder component, any one can be used as long as it has a melting point of 100 ° C. or less and can impart strength to a formulation commonly used in the art. For example, it is preferable that melting | fusing point, such as polyethyleneglycol, poloxamer, HCO, glycerin, propylene glycol, glycerides, derivatives thereof, and mixtures thereof, is 100 degrees C or less. Preferred examples include polyethylene glycol 200, 300, 400, 600, 1000, 1500, 2000, 3000, 4000, 6000, 8000 and 20000, poloxamer 188, 237, 338 and 407, HCO-50, HCO-60, glycerin, glycerol Reel behenate, glyceryl monostearate, glyceryl monooleate, propylene glycol, medium chain triglycerides, fatty acid glycerides and the like.

The disintegrant component is a component for disintegrating the fast-acting preparation more rapidly in the oral cavity, specifically, crosslinked polyvinylpyrrolidone, crosslinked carboxymethyl cellulose, sodium starch glycolate, calcium carboxymethyl cellulose, these Mixtures thereof and the like can be used.

As the lubricant component, magnesium stearate, talc, silica, sodium stearyl fumarate, valine, sucrose fatty acid ester, hydrogenated castor oil, mixtures thereof and the like can be used.

In addition, as a pharmaceutical excipient to aid in formulation, sweetener components such as aspartame, stevioside, sucralose, acesulfame, filler components such as microcrystalline cellulose, calcium phosphate, calcium carbonate, starch and the like can be used.

The pharmaceutically acceptable additive may be used in an amount of 0.01 to 50 parts by weight, preferably 0.1 to 30 parts by weight, based on 100 parts by weight of the mixed powder.

In the present invention, the pharmaceutically active ingredient, sugars or sugar alcohols and any pharmaceutically acceptable additives may be mixed by dry mixing or wet mixing. The dry mixing method in which all components are homogeneously mixed in a mixer, and the wet mixing method in which wet granules are made of some or all of the ingredients and then dried again may be used.

Subsequently, the resultant mixed powder is filled into the packaging material, in particular, in the lower pocket film for packaging, and as the material of the packaging material, aluminum, polyvinyl chloride (PVC) or polyvinylidene chloride (PVDC) is suitable. In consideration of the subsequent high temperature heating process, an aluminum material that can withstand temperatures ranging from 200 to 1,000 ° C. is more preferred. If PVC or PVDC materials are used, the packaging material may be deformed by heating, but in this case, the packing material may be prevented by selectively heating only the filled powder. To prevent the patient or consumer from confusing the medicine (to ensure grain identification), the molded lower pocket film can be used as a packaging material to mold or emboss the embossed or engraved letters or patterns on the product surface. Misuse can be prevented beforehand.

Step (B)

The filler obtained in step (A) is heated to 200 to 1,000 ° C. for 1 to 60 seconds, preferably 1 to 30 seconds, using radiant heat to form a rapid preparation having a form from the mixed powder. At this time, since the rapid preparation may stick to the packaging material contacting portion depending on the properties of the mixed powder and the heating conditions, it is prevented by appropriately adjusting the composition ratio and heating conditions of the mixed powder.

In the present invention, the degradation of the pharmaceutically active ingredient can be minimized by exposing the fill to very high temperatures for a few seconds to several tens of seconds, the exposure time being appropriately selected depending on the type of ingredient used in the mixed powder. As a heating means, a halogen lamp, an infrared (IR) irradiator, a heating tunnel, etc. can be used, and a halogen lamp is preferable among these.

The top cover film may then be adhered to the bottom pocket film of the generic formulation having a form formed by heating to complete packaging of the product. Aluminum is suitable as a material of the cover film, but any material can be peeled or peeled off easily.

The form of the fast-acting preparation according to the present invention may be variously selected depending on the purpose of tablets, pills, capsules or powders, but preferably may be a tablet.

As described above, according to the method of the present invention, a rapid oral dosage preparation for oral administration which is high in compliance with medications and rapidly dissolved in the oral cavity can be produced easily and economically without deteriorating the properties and physical properties of the preparation by forcible passage formation. Can be.

According to the present invention, a method of manufacturing and packaging a rapid preparation for oral administration which is high in compliance with medications and rapidly dissolves in the oral cavity without degrading the properties and physical properties of the preparation by forcibly forming a passage is a series of single processes. Through the simple and economical effect can be manufactured.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

Example  One

After homogeneously mixing 20 mg of pamotidine as a pharmaceutically active ingredient per sugar and 300 mg of xylitol as sugar alcohols, the mixed powder was filled into a lower pocket film made of molded aluminum. Subsequently, the filler was heated with an infrared lamp at about 800 ° C. for 6 seconds to form a fast preparation having a form, and then the top cover film made of aluminum was attached to the bottom pocket film to prepare the fast preparation.

Example  2

Rapid preparations were prepared in the same manner as in Example 1, except that the packing was heated for 20 seconds using an infrared lamp at about 400 ° C.

Example  3

Rapid preparations were prepared in the same manner as in Example 1 except that the packing was heated for 15 seconds using an infrared lamp at about 600 ° C.

Example  4

Rapid preparations were prepared in the same manner as in Example 1 except that the packing was heated for 30 seconds using an infrared lamp at about 400 ° C.

Example  5

Rapid preparations were prepared in the same manner as in Example 1 except that the packing was heated for 2 seconds using an infrared lamp at about 1000 ° C.

Example  6 to 10

As the sugar alcohols, instead of 300 mg of xylitol, each fast-acting formulation was prepared in the same manner as in Example 1 except that 300 mg of sorbitol, 150 mg of xylitol and 150 mg of sorbitol, 300 mg of maltitol, 300 mg of mannitol, and 300 mg of erythritol were used, respectively.

Example  11 to 20

Instead of xylitol as sugar alcohols, except that sugar, lactose, glucose, sucrose, fructose, maltose, paratinose, rebulose, maltodextrin, trehalose and dextrose were used in the same amount as xylitol, respectively. Each fast preparation was prepared in the same manner as in Example 1.

Example  21 to 45

As a pharmaceutically active ingredient, instead of 20 mg of famotidine, 50 mg of tramadol hydrochloride, 50 mg of ibuprofen, 50 mg of dexibuprofen, 50 mg of aspirin, celecoxib 50mg, 20 mg of vadenafil hydrochloride, 5 mg of amlodipine, 50 mg of ceftinir, 50 mg of ondansetron 4 mg, sildenafil 50 mg, donepezil 5 mg, galantamine 4 mg, hydrochloric acid tamsulosin 0.2 mg, sumatriptan 4 mg, montelukast 4 mg, loratadine 10 mg, glymepiride 2 mg, fexofenadine 30 mg, torsemide 5 mg, topiramate 50 mg, risperidone 2 mg, olanzapine 10 mg Each fast preparation was prepared in the same manner as in Example 1 except that 2.5 mg of zolmitriptan and 5 mg of montelukast were used.

Example  46 to 51

As in Example 1, except that PEG 6000 10 mg, PEG 6000 20 mg, PEG 6000 40 mg, Poloxamer 188 10 mg, Poloxamer 188 20 mg, and Poloxamer 188 40 mg were added to the mixed powder as the low melting point binder, respectively. The formulation was prepared.

Example  52

As sugar alcohols, instead of 300 mg of xylitol, 300 mg of mannitol was dissolved in 10 mg of water and 10 mg of ethanol to prepare wet granules, and a rapid preparation was prepared in the same manner as in Example 1 except that the dried product obtained by drying was used.

Example  53

As a sugar alcohol, instead of 300 mg of xylitol, a mixture of 150 mg of xylitol and 150 mg of mannitol was dissolved in 5 mg of water and 10 mg of ethanol to prepare wet granules, and the same formulation as in Example 1 was used except that the dried product obtained by drying was used. Was prepared.

Example  54

As sugar alcohols, instead of 300 mg of xylitol, a mixture of 50 mg of xylitol and 250 mg of mannitol was dissolved in a mixed solvent of 5 mg of water, 10 mg of ethanol and 5 mg of medium chain triglyceride (MTC oil) to prepare wet granules, and then dried. Except for using, the same formulation was prepared in the same manner as in Example 1.

Example  55

As sugar alcohols, instead of 300 mg of xylitol, a mixture of 50 mg of xylitol and 250 mg of mannitol was dissolved in a mixed solvent of 5 mg of water, 10 mg of ethanol and 5 mg of medium chain triglyceride (MTC oil) to prepare wet granules, and then dried on a dried product. A rapid preparation was prepared in the same manner as in Example 1, except that 30 mg of cross-linked polyvinylpyrrolidone was used in combination.

Comparative example  One

Commercially available gasster oral disintegrating tablets (famotidine 20 mg, Dong-A Pharmaceutical) were used as comparative examples. At this time, the gastric oral disintegrating tablet is prepared using the WOWTAB (WOWTAB) technology.

Test Example  One : Speed  Formulation Disintegration  Property evaluation

[Disintegration time]

Purified water was tested according to the disintegration test method of the Korean Pharmacopoeia General Test Methods. The time required for the tablet to completely dissolve and disappear.

[In vitro disintegration time]

A 90 mm diameter filter paper was placed on a petri dish (100 x 10 mm), 7 mL of purified water was poured into the plate, and the plate was tilted while being careful not to bubble. When the filter paper was all wet, the tablets were placed on a plate and the purified water was increased by the capillary action. Six tablets were tested in each dish to determine the time required for the tablets to fully wet.

[Intraoral disintegration time]

When a healthy adult man puts the tablet on the tongue in the oral cavity and rubs it gently without putting water in the oral cavity, the time until complete disintegration and dissolution is measured.

The disintegration characteristics evaluation results of the present invention fast-acting preparation prepared in Example and the gasster oral disintegrating tablet of Comparative Example are shown in Table 1 below.

As can be seen from the results of Table 1, the fast-acting preparation of the present invention prepared by the Example was softly dissolved in the oral cavity between 2 to 33 seconds and excellent in medication compliance so that it can be taken without water. The castor oral disintegrating tablets used as the process took more than 40 seconds to disintegrate in the oral cavity.

On the other hand, the pharmaceutical packaging device that can be prepared in large quantities for the preparation of a rapid-release preparation by applying the production method of the present invention will be described in detail.

A general pharmaceutical packaging device is a blister packaging machine, which is a blister packaging machine, which is formed from a flat film made of synthetic resin or a metal, and forms a container shape. Refers to a packaging technique that produces one packaging unit by punching and cutting. Such blister packaging was originally developed to package tablets or capsules of pharmaceutical companies in one pack, and is used in confectionery, cosmetics, or household goods in large quantities. Since blister packaging uses transparent film compared to other packaging methods, it is easy to identify the product, and by packaging the film, the packaging shape can be freely changed by a shape or molding tool such as a product. Excellent product protection by using, easy to open the product when in use has the advantage that anyone can easily use, carry.

Conventional pharmaceutical packaging device is configured as follows approximately.

(1) Molded film supply unit: Supplying a flat molded film for the manufacture of the lower pocket film for packaging, the uncoiler (unoiler) to release and supply the molded film in general, and pulled and transported the molded film from the uncoiler at a constant speed And draw-off means.

(2) Film forming part: seating a mold manufactured in a shape corresponding to the shape of the product, placing the molded film on the mold, and forming a pocket recessed on the molded film by pressing the molding pressing rod downward. In order to improve film formability, it can be provided with the preheating part which preheats a molded film previously.

(3) Content input part: A product is provided with a hopper for storing the product and puts the product into the pocket of the lower pocket film.

(4) Sealing part: The upper cover film for sealing is attached to the lower pocket film into which the contents were put, and the uncoiler and sealing machine which rolled up the cover film in roll form are provided.

(5) Cutting part: It cuts the product into a certain packing unit. If necessary, embossing machine to emboss the product number or manufacturing date, slitting machine to engrave the cutting line, and punching. (punching) may include a punching machine and the like.

(6) Control unit: It is installed on the front of the device to be operated by the operator to control the operation, it can be implemented as a control panel (control panel).

Looking at the operation of such a drug packaging device, first, the molded film wound on the uncoiler of the molded film supply unit enters at a constant speed, the molded film enters the preheating unit of the film forming unit is preheated to a temperature suitable for molding, and immediately It is pressed by the molding pressure bar to form a container-shaped pocket on which the contents can be accommodated on the molded film. In this way, the formed film having the pocket becomes a lower pocket film for packaging, and then the contents (pills, etc.) are introduced into the pocket by the contents input portion, and the lower pocket film into which the contents are injected goes to the sealing portion and is integrally compressed with the upper cover film. It seals the contents, and then reaches the cut portion, which is cut into a predetermined packaging unit.

Pharmaceutical packaging device applied to the present invention has the above configuration and operation manner in principle, the specific form and function is not limited. In other words, if only basic blister packaging function can be applied to the present invention.

1 is a block diagram of a pharmaceutical packaging device for the preparation of a rapid-release formulation for oral administration according to the present invention.

The pharmaceutical packaging device 100 for the preparation of the oral dosage form for oral administration according to the present invention is basically a molded film supply unit 110, a film forming unit 120, a sealing unit ( 170, a cutting unit 180, and a control unit 190, and presses the mixed powder 20 or the mixed powder 20 to form a tablet 22 in the pocket 10a of the lower pocket film 10. It has a medicine injecting unit 130 to replace the above-described contents input unit to be added, and additionally provided with a heating unit 160 for heating and melt-bonding the fillings injected into the lower pocket film (10).

Accordingly, the molding film supply unit 110, the film molding unit 120, the drug injection unit 130, the heating unit 160, the sealing unit 170, and the cutting unit 180 are sequentially disposed.

The drug injecting unit 130 is a lower pocket film 10 in which a raw material mixed powder 20 containing a pharmaceutically active ingredient and sugars or sugar alcohols or a tablet 22 pressurized with the mixed powder 20 is already molded. Into the pocket 10a.

2 is a schematic view of one configuration form of the drug input unit 130.

The drug injecting unit 130 fills and pressurizes the mixed powder 20 in an appropriate amount at the 'powder pressurized position' to make the mixed powder 20 into a tablet 22 having a form, and then moves to the 'drug discharge position'. The tablet 22 is thrown into the pocket 10a of the lower pocket film 10 previously conveyed.

The configuration according to the example, the disk (disk) having the two or more filling holes (132a) sequentially positioned in the 'powder pressurized position' and the 'medicine discharge position' is loaded with the mixed powder 20 on the upper surface ( 132 and the lower filling hole 132a is closed and the lower filling hole 132a has an opening hole 134a for its opening and is provided on the lower side of the filling disc 132; Pressing rods 136 and filling disks provided on the upper side to correspond to every filling hole 132a and simultaneously descending into the filling holes 132a to press the mixed powder 20 or discharge the tablets 22 and then rise. And a hopper 138 for supplying the mixed powder 20 on the 132.

Here, the filling disk 132 is a circular plate, and has two or more vertically penetrating filling holes 132a spaced at equal intervals along the circumferential direction, and the filling disc 132a is rotated so that the filling holes 132a and the 'powder pressurized position' and the like. Sequentially move to 'Drug Release Location'.

Therefore, in the state where the mixed powder 20 is supplied from the hopper 138 and loaded on the filling disk 132, the filling disk 132 is rotated so that one side of the filling hole 132a is pressurized from the drug discharge position. A portion of the mixed powder 20 loaded in the process of moving to the position 'naturally flows into the filling hole 132a, and then the filling hole 132a is stopped at the' powder pressurized position '. Thereafter, the pressure bar 136 is lowered into the filling hole 132a to compress the mixed powder 20 introduced therein into a tablet 22 having a bonding strength to some extent and then rise. Subsequently, the filling disk 132 is rotated again by a predetermined angle so that the filling hole 132a is stopped at this time the 'drug discharge position', and then the pressure bar 136 is lowered into the filling hole 132a again and then inside. The tablet 22 is pushed downward and discharged, and the discharged tablet 22 is dropped into the pocket 10a of the lower pocket film 10 previously transferred to the 'drug discharge position'.

Of course, all the pressure rods 136 are elevated at the same time, 'powder pressurization' and 'drug discharge' is carried out at the same time.

In summary, the operation of the drug injecting unit 130 includes the step of filling the mixed powder 20, the step of pressing the filled mixed powder 20, and the step of discharging the tablet 22.

At this time, the filling and pressing step may be carried out in two or more multi-steps to meet the dose of the drug, for this purpose is provided with the required number of filling holes (132a) and the pressure rod 136, the rotation of the filling disk 132 The steps can be multiplied as much.

Of course, in multistage filling and pressurization steps, if the required amount of the desired product, ie, the active ingredient of the fast dissolving tablet, is low or the cohesion of the active ingredient is high, the number of steps can be reduced.

In addition, when the tablet 22 is made in the 'powder pressurized position' and when the made tablet 22 is transferred from the 'powder pressurized position' to the 'drug ejection position' and at the point of time when stopped at the 'drug ejection position', The upper cover for the lower pocket film 10 and the marketability of the tablet 22 and later to be carried out by blocking the inflow of the surrounding mixed powder 20 into the filling hole 132a in which the tablet 22 is located. In order to ensure the sealing property of the film, as shown in Figure 3, the inlet blocking may be in the form of a plate on the upper surface of the filling disk 132 from the 'powder pressurized position' front side position to the rear side position of the 'drug discharge position' Means 137 may be provided.

For reference, reference numeral 112 denotes a guide rail block 112 for guiding the movement of the lower pocket film 10, and reference numeral 139 denotes an outflow of the mixed powder 20 loaded on the filling disc 132. Outflow blocking plate to block.

In addition, in the above, after the mixed powder 20 is made into the tablet 22 and then into the lower pocket film 10, the mixed powder 20 may be simply added into the lower pocket film 10 as it is. .

On the other hand, the heating unit 160 by heating the filling in the lower pocket film 10 to 200 to 1,000 ℃ for a very short time of several seconds to several tens of seconds to melt-bond the filler while minimizing the decomposition of the active pharmaceutical ingredients, In the case of the mixed powder form, the mixed powders are melt-bonded to each other to form a gathered tablet form, and in the case of tablet form, the aggregation power may be further enhanced.

4 is a schematic view of one configuration form of the heating unit 160.

The heating unit 160 is provided on the upper side with respect to the lower pocket film 10 that is moved and stopped on the guide rail block 112 to generate heat to heat the heating means for heating the melt in the lower pocket film 10 by bonding. 162 and a shutter which opens and closes the progress of the high heat from the heat generating means 162 by advancing and retreating between the heat generating means 162 and the lower pocket film 10 to adjust the heating exposure time and to allow repeated heating ( shutter) means (164).

Here, as the heat generating means 162, a halogen lamp, an infrared lamp or the like capable of instantaneous heating of 200 ° C. or more may be used, and a plurality of them may be used depending on the situation.

Shutter means 164 may be implemented as a plate that covers the lower pocket film 10 to block the exposure to the heating means 162, the exposure time according to the retreat is the type of the pharmaceutical component and the lower pocket film ( 10) can be adjusted according to the material.

Therefore, the lower pocket film 10 proceeds sequentially, and the filling means in the lower pocket film 10 may be repeatedly heated to a predetermined exposure time while the shutter means 164 is opened and closed.

Furthermore, the pharmaceutical packaging device 100 for the preparation of the rapid-release preparation for oral administration according to the present invention, as shown in Figure 5, the pressing portion 140 between the drug injecting unit 130 and the heating unit 160 The pressing unit 140 may be provided to the tablet 22 having the same shape as the shape of the pocket 10a by pressing the filling material introduced into the pocket 10a of the lower pocket film 10 through the medicine injecting unit 130. Make it.

As shown in FIG. 6, the pressing part 140 may include a tamping rod 142 that descends into the pocket 10a of the lower pocket film 10, presses the filling material, and then rises. have.

At this time, by pressing the filling in multiple stages to make the form closer to the shape of the pocket (10a) can be repeatedly pressed by placing the tamping rods 142 before and after, primarily on the drawing mainly press the outer portion of the mixture drug Note is shown for primary tamping rods and secondary tanking rods that primarily press the center of the mixture drug.

In addition, the tamping rod 142 may be rotated at a fine angle while the filling material is pressed, and thus the filling material may be uniformly spread without being biased in the pocket 10a.

In addition, the drug packaging device 100 for the preparation of a rapid-release drug preparation for oral administration according to the present invention, as shown in Figure 7, the suction (suction) between the drug injection unit 130 and the heating unit 160 150 may be provided, and the section 150 may generate suction pressure on the lower pocket film 10 into which the filling material is injected to forcibly suck unnecessary fine powder attached to the lower pocket film 10. By removing it, the drug property of a chemical | medical agent is improved and the sealing property of the upper cover film with respect to the lower pocket film 10 is ensured later.

As shown in FIG. 8, the configuration of the cushion unit 150 is connected to a vacuum utility line or a vacuum pump in the factory and generates a suction nozzle 152 for generating a vacuum suction pressure to the lower pocket film 10. And a screen net 154 provided to intervene between the suction nozzle 152 and the lower pocket film 10 to prevent the filling from being pulled up by the vacuum suction pressure.

In this case, the suction nozzle 152 may be operated to move up or down with respect to the lower pocket film 10.

It will be described a general operation example of the pharmaceutical packaging device 100 for the preparation of the oral dosage form for oral administration according to the present invention having the configuration as described above.

First, the molded film is supplied from the molded film supply unit 110 at a constant speed, and the molded film is preheated in the film forming unit 120 and then press-molded to form a container-shaped pocket 10a on the molded film. Thus, the lower pocket film 10 is produced.

Thereafter, the filling material is introduced into the pocket 10a of the molded lower pocket film 10 in the form of a powder or tablet through the medicine injecting unit 130, and then the pressing unit 140 of the lower pocket film 10 The filling in the pocket 10a is pressed into a tablet 22 that is identical in shape to the pocket 10a.

Thereafter, the powder that is unnecessarily attached to the lower pocket film 10 through the cushioning unit 150 is removed by vacuum suction.

Then, the filler in the lower pocket film 10 is heated and melt-bonded in the heating unit 160 to be formulated into an oral fast-acting tablet in tablet form having a firm binding force.

Thereafter, the lower pocket film 10 having the oral rapid tablet contained therein is compressed and sealed with the upper cover film in the sealing unit 170 to complete packaging, and then cut in a predetermined packing unit in the cutting unit 180. do.

Finally, the oral rapid-release product completed up to packaging is slowly cooled to room temperature in the package.

In this way, oral rapid tablets can be conveniently and economically mass-produced through a series of single processes.

In addition, according to the present invention, it is possible to make the same product even if the heating is carried out after the packaging is completely attached to the top cover film without heating through the heating unit 160 as described above. Obviously, for this purpose, after the packaging of the oral fast-acting product, it can be charged into a heating chamber (chamber) to be heated separately.

It will be appreciated by those skilled in the art that changes may be made to the present invention without departing from the spirit and scope of the invention as defined by the appended claims.

1 is a block diagram for the configuration of a pharmaceutical packaging device for the preparation of a rapid-release formulation for oral administration according to the present invention,

Figure 2 is a cross-sectional view showing a medicament input unit of the pharmaceutical packaging device for the preparation of a rapid-release formulation for oral administration according to the present invention,

Figure 3 is a schematic perspective view showing the main portion of the drug injector of the drug packaging device for the preparation of the rapid-release preparation for oral administration according to the present invention,

Figure 4 is a cross-sectional view showing a heating portion of the pharmaceutical packaging device for the preparation of the oral formulation for oral administration according to the present invention,

Figure 5 is a block diagram for the configuration of a pharmaceutical packaging device for the preparation of a rapid-release formulation for oral administration according to another embodiment of the present invention,

Figure 6 is a cross-sectional view showing the pressing part of the pharmaceutical packaging device for the preparation of the oral formulation for oral administration according to another embodiment of the present invention,

Figure 7 is a block diagram for the configuration of a pharmaceutical packaging device for the manufacture of a rapid-release formulation for oral administration according to another embodiment of the present invention,

Figure 8 is a cross-sectional view showing a cushioning portion of the pharmaceutical packaging device for the preparation of a rapid-release formulation for oral administration according to another embodiment of the present invention.

<Description of the symbols for the main parts of the drawings>

10: lower pocket film 10a: pocket

20: mixed powder 22: tablets

100: pharmaceutical packaging device 110: molded film supply unit

112: guide rail block 120: film forming part

130: drug input unit 132: filling disk

132a: Filling hole 134: Lower disc

134a: opening hole 136: pressure rod

137: inflow blocking means 138: hopper

139: spill blocking plate 140: pressing part

142: tamping rod 150: cushion portion

152: cushion nozzle 154: screen network

160: heating unit 162: heating means

164: shutter means 170: sealing part

180: cutting unit 190: control unit

Claims (28)

delete delete delete delete delete delete delete delete delete delete delete delete delete delete A pharmaceutical packaging device that manufactures and packages a rapid-release preparation for oral administration in a single process, Molded film supply unit for supplying a molded film; A film molding part for molding the molded film to produce a lower pocket film having a container-shaped pocket; A medicine injecting unit filling and injecting a medicine into the pocket of the lower pocket film; A heater unit for heating and melting bonding the filling material in the molding pocket film; A sealing part attaching an upper cover film to the lower pocket film; Cutting portion for cutting the packaging material of the lower pocket film and the upper cover film attached in a predetermined unit; And A control unit for operation control; Pharmaceutical packaging device for packaging of the oral dosage form for oral administration comprising a. delete 16. The method of claim 15, The medicine input unit, A filling disc having the two or more filling holes sequentially positioned at a 'powder pressurized position' and a 'drug discharge position' having the mixed powder loaded on an upper surface thereof; A lower disc provided below the filling disc to close the filling hole on one side and open the filling hole on the other side; It is provided on the upper side corresponding to each of the filling hole at the same time descending into the filling hole to press the mixed powder in the filling hole in the 'powder pressing position' and in the filling hole in the 'drug discharge position' A pressure rod that rises after discharging the tablets; And A hopper for supplying the mixed powder on the filling disc; Characterized in that, comprising a pharmaceutical packaging device for the packaging of the oral dosage form for oral administration. The method of claim 17, The filling disc is rotated, Pharmaceutical packaging device for packaging the oral dosage form for the oral administration, characterized in that the mixed powder loaded in the rotation process is introduced into the filling hole. The method of claim 17, The 'powder pressing position' is formed at two or more places, Pharmaceutical packaging device for packaging the oral dosage form for the oral administration, characterized in that the mixed powder inlet, pressurized in multiple stages. The method of claim 17, The medicine input unit, An inlet blocking means provided on the filling disc in the 'powder discharge position' rear side position at the 'powder pressurization position' front side to prevent the inflow of the mixed powder into the filling hole; Further comprising, Pharmaceutical packaging device for packaging of the oral formulation for oral administration. 16. The method of claim 15, The heating unit, Heating means for generating heat to heat the filling in the lower pocket film; And Shutter means for entering and exiting between the heat generating means and the lower pocket film to adjust the heating exposure time; Characterized in that, comprising a pharmaceutical packaging device for packaging of the oral dosage form for oral administration. 22. The method of claim 21, The heat generating means, Pharmaceutical packaging device for the packaging of oral dosage form for oral administration, characterized in that the halogen lamp or infrared lamp. 16. The method of claim 15, A pressing part which presses the filling in the pocket of the lower pocket film to form the same shape as the pocket shape through the medicine input part; Further comprising, Pharmaceutical packaging device for packaging of the oral dosage form for rapid administration. 24. The method of claim 23, The pressing portion, A tamping rod that descends into the pocket of the lower pocket film and rises after pressing the filling material; Characterized in that, comprising a pharmaceutical packaging device for packaging of the oral dosage form for oral administration. 25. The method of claim 24, The pressing portion, Pharmaceutical packaging device for the manufacture of a rapid-release formulation for oral administration, characterized in that pressing sequentially two or more times using the tamping rods arranged sequentially. 25. The method of claim 24, The tamping rod of the pressing portion, And lowering the lower pocket film into the pocket so as to rotate the pressed material while pressing the filler to uniformly spread the filler in the pocket. The method of claim 15 or 23, A suction unit generating suction pressure on the lower pocket film to suck and remove unnecessary fine powder attached on the lower pocket film; Further comprising, Pharmaceutical packaging device for packaging of the oral dosage form for rapid administration. 28. The method of claim 27, The section, A suction nozzle for generating a vacuum suction pressure on the lower pocket film; And A screen net provided between the suction nozzle and the lower pocket film to prevent the filling in the pocket from being pulled up by a vacuum suction pressure; Characterized in that, comprising a pharmaceutical packaging device for packaging of the oral dosage form for oral administration.

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