HK1165769A1 - Packaging machine for preparation of rapid disintegrating agents for oral administration - Google Patents

Abstract

A method and packaging machine for preparing rapidly disintegrating formulations for oral administration are disclosed. The present invention is characterized in that a powdery mixture including a pharmaceutically active ingredient and a sugar or a sugar alcohol powder is filled into a packaging material and, thereafter, the mixture, filled in the packaging material, is heated. The present invention can simply and economically prepare an oral formulation which undergoes rapid disintegration in the oral cavity and provides for high-quality administration to patients.

Description

Packaging machine for preparing rapid disintegrating agent for oral administration

The present application claims the priority of Korean patent application No.10-2007-0063757 filed on 27.6.2007; the present application is a divisional application of chinese patent application No.200880022469.8 filed on day 12, month 28, 2009.

Technical Field

The present invention relates to a method and a packaging machine for preparing an oral dosage form that rapidly disintegrates in the oral cavity, and a rapidly disintegrating agent prepared thereby.

Background

Fast disintegrating agents are usually prepared by different methods using lyophilization, disintegrating agents, sublimation-like materials, humidification or dehumidification.

For example, U.S. Pat. nos. 5631023 and 5976577 disclose a formulation obtained by subjecting a solution containing a drug to lyophilization. This formulation was recently used to prepare products marketed by the companies Merck, GlaxoWelcome and Schering-Plough under the trademarks Pepcid RPD (a famotidine formulation), Zofran zydis (an Otamcinolone formulation) and Claritin Reditabs, respectively. These preparations disintegrate in the oral cavity within 2 to 3 seconds, but the process for preparing them requires the use of special equipment and packaging materials, resulting in a reduction in yield and high manufacturing costs.

To solve this problem, International patent publication No. WO99/47126 proposes a process for preparing a preparation free from residual organic solvents by compressing an active ingredient with a water-soluble polymer binder to form a tablet, and humidifying the resulting tablet under high humidity conditions, followed by drying. This method is known as the WOWTAB technique developed by Yamanouchi pharmaceutical corporation of japan. Further, international patent publication No. WO93/12769 discloses a method for preparing a dosage form by placing a suspension containing an active ingredient, agar and a sugar in a mold, and then drying the suspension at 30 ℃ under 760 mmHg. But this method brings about low productivity and non-uniformity in product quality.

Alternatively, the Orasolv technology for preparing fast disintegrating agents was developed by Cima laboratories and disclosed in U.S. patents nos. 5178878 and 6024981. The commercial product obtained by the Orasolv technology is given the trademark Zimig rapidelt (a zolmitriptan dosage form) marketed by the company Astrazeneka, but it does not produce a satisfactory disintegrating effect in the mouth and gives an uncomfortable feeling upon taking because of the generation of bubbling gas.

U.S. patent No. 3885026 discloses a method for making porous tablets by mixing active excipients such as urethane, urea, ammonium carbonate and naphthalene with other tablet components, compressing the mixture to form a tablet, and heating the tablet to remove the active excipients.

Still further, U.S. patent No. 4134943 describes a method for preparing porous tablets by mixing a solvent (water, cyclohexane, benzene, tertiary butanol) having a melting point between-30 ℃ and 25 ℃ with tablet components, cooling the mixture to solidify the solvent, compressing the solid mixture to form tablets, and then removing the solvent therefrom by evaporation, but such porous tablets may be toxic due to residual excipients or organic solvents.

As described above, the conventional fast disintegrants are prepared by forming a tablet containing a specific material that can be removed by purification, evaporation or dehumidification, and then removing the corresponding specific material therefrom, so that they become porous and allow rapid penetration of saliva. Such conventional dosage forms, however, have arbitrarily formed pores, resulting in significant deterioration of physical properties or undesirable dimensional changes.

Therefore, there is a need for the development of a rapid disintegrating agent which can be easily produced and provides a comfortable feeling to a patient when taken without causing the problems of the above-mentioned conventional methods.

Disclosure of Invention

It is therefore an object of the invention to provide a simple method and packaging machine for preparing an oral formulation which produces a rapid disintegration in the oral cavity and provides improved comfort to the patient when taking it.

In accordance with one aspect of the present invention, there is provided a method for preparing a fast disintegrant for oral administration, comprising: (A) mixing the pharmaceutically active ingredient with sugar or sugar alcohol powder to obtain a powdery mixture, and filling the powdery mixture into a packaging material; and (B) heating the mixture filled in the packaging material obtained in step (A) to solidify the mixture.

In accordance with another aspect of the present invention, there is provided a rapid disintegrant for oral administration prepared by the above method.

In accordance with still another aspect of the present invention, there is provided a packaging machine for preparing a fast disintegrant for oral administration, comprising: the film conveying unit is used for conveying the formed film; a film forming unit for forming the formed film to form a bottom pocket film (lower pocket film) designed with a pocket in the shape of a container; a drug material delivery unit to fill a powdery mixture or a tablet into the pocket of the bottom pocket film, which is formed by pressing the powdery mixture to have a predetermined shape; a heating unit for heating the filled mixture or tablet, thereby melting and combining the filled mixture or tablet; and a sealing unit for attaching an upper cover film (upper cover film) to the bottom pocket film.

In accordance with the present invention, an oral preparation which produces rapid disintegration in the oral cavity and allows for improved comfort when taken by a patient, can be prepared in a simple and economical manner through a single processing route, while avoiding deterioration of desired physical properties or generation of undesirable dimensional changes caused when a conventional method including any pore-forming step is used.

Drawings

The above and other objects, features and advantages of the present invention will be more clearly understood from the following detailed description taken together with the accompanying drawings, in which:

fig. 1 is a block diagram showing the construction of a packing machine for preparing a fast disintegrant for oral administration according to an embodiment of the present invention;

fig. 2 is a cross-sectional view of a drug material delivery unit of a packing machine for preparing a fast disintegrant for oral administration according to the present invention;

fig. 3 is a perspective view showing a key part of a drug material delivery unit of a packing machine for preparing a fast disintegrant for oral administration according to the present invention;

fig. 4 is a cross-sectional view of a heating unit of a packing machine for preparing a fast disintegrant for oral administration according to the present invention;

fig. 5 is a block diagram showing the construction of a packing machine for preparing a fast disintegrant for oral administration according to another embodiment of the present invention;

figure 6 is a cross-sectional view of a compression unit of a packaging machine for preparing a fast disintegrating dosage form for oral administration according to the embodiment of figure 5;

fig. 7 is a block diagram of a structure of a packing machine for preparing a rapidly disintegrating agent according to another embodiment of the present invention;

fig. 8 is a cross-sectional view of a pumping unit of a packing machine for preparing a fast disintegrant for oral administration in accordance with the embodiment of fig. 7.

Detailed Description

The present invention will be described in detail below.

The inventive method is characterized in that a mixture of a pharmaceutically active ingredient and sugar or sugar alcohol having many intrinsic pores is melt-combined, and a rapid disintegrant having intrinsic pores is formed by filling the mixture into a packaging material (step a) and heating (step B), unlike the conventional method of arbitrarily producing pores by purification, evaporation or drying.

The process of the invention does not result in deterioration of physical properties of the formulation or undesirable dimensional changes and it is very simple and inexpensive.

< step (A) >

A composition (mixed powder) for preparing the inventive preparation, which comprises a pharmaceutically active ingredient and a sugar or sugar alcohol, and which may further comprise a pharmaceutically acceptable additive.

Thus, the ingredients of the inventive composition for a fast dispersing formulation are described in detail below: selected from the group consisting of: tamsulosin, sumatriptan, zolmitriptan, rizatriptan, loratadine, fexofenadine, glimepiride, tolazamide, furosemide, gabapentin, pregabalin, valproate, topiramate, carbamazepine, lamotrigine, oxcarbazepine, selegiline, risperidone, ziprasidone, quetiapine, olanzapine, clozapine, paliperidone, pharmaceutically acceptable salts and mixtures thereof.

(1) Pharmaceutically active ingredients

Antipyretic, analgesic or anti-inflammatory agents, for example tramadol, ibuprofen, dexibuprofen, aspirin, acetaminophen, indomethacin, diclofenac sodium, ketoprofen, isopropylantipyrine, phenacetin, fluprofen, phenylbutazone, etodolac, celecoxib, etoricide and pharmaceutically acceptable salts thereof.

② antiulcer agent, such as cimetidine, famotidine, ranitidine, nizatidine, roxatidine and pharmaceutically acceptable salts thereof.

③ cardiovascular or vasodilatory agents, such as nifedipine, amlodipine, verapamil, captopril, diltiazem hydrochloride, propranolol, oxprenolol, nitroglycerin, enalapril and pharmaceutically acceptable salts thereof.

Antibiotics, such as ampicillin, amoxicillin, cephalexin, cefuroxime, cefdinir, cefadroxil, cefprozil, cefpodoxime, cefditoren, cefaclor, cefixime, cephradine, chlorocarbaceph, cefbutan, ceftriazine, Cefcarpen, erythromycin, tetracyclines, quinolones and pharmaceutically acceptable salts thereof.

Antitussives or antiasthmatics, for example theophylline, aminopyrine, codeine, phosphates, methamphetamine hydrochloride, dextromethorphan, noscapine, salbutamol, ambroxol, clenbuterol, terbutaline, montelukast and pharmaceutically acceptable salts thereof.

Sixth, antiemetics or gastric function modulators, such as ondansetron, metoclopramide, domperidone, trimebutine maleate, cisapride, levosulpiride, and pharmaceutically acceptable salts thereof.

(vii) agents for the treatment of impotence, such as sildenafil, vardenafil, tadalafil, udenafil and pharmaceutically acceptable salts thereof.

(viii) dementia-treating agents such as donepezil, galantamine, rivastigmine, acetylcarnitine, memantine, Zaliprodene and pharmaceutically acceptable salts thereof.

In addition to the above ingredients, the other active ingredients may comprise an agent for treating benign prostatic hyperplasia such as tamsulosin; an agent for treating periodic migraine such as sumatriptan, zolmitriptan and rizatriptan; a psychostimulant; an antibiotic agent; an antihistamine such as loratadine and fexofenadine; an oral antidiabetic agent such as glimepiride; an antiallergic agent; a contraceptive agent; a vitamin compound; an anticoagulant agent; a muscle relaxant; an agent for improving cerebral metabolism; an antidiuretic agent such as tolisamide and furosemide; an anti-spasmodic agent such as gabapentin, pregabalin, valproate, topiramate, carbamazepine, lamotrigine, oxcarbazepine; a parkinson's disease therapeutic agent such as selegiline; an antipsychotic agent such as risperidone, ziprasidone, quetiapine, olanzapine, clozapine, and paliperidone; and pharmaceutically acceptable salts thereof; and a biological vaccine.

The active ingredient may be employed in an amount of 0.01 to 90%, preferably 0.02 to 70%, by weight based on the total weight of the powdered mixture.

(2) Sugars or sugar alcohols

The sugar or sugar alcohol functions to maintain the shape of the preparation, determine its dissolution rate, and provide sweetness, solubility and a comfortable feeling in the mouth. It is therefore preferred that the sugar or sugar alcohol is sweet and water soluble. Representative examples thereof include lactose, glucose, sucrose, fructose, mannitol, sorbitol, xylitol, erythritol, ribulose, maltitol, maltose, maltodextrin, palatinose (Paratinose), trehalose, dextran, and one mixture thereof.

The sugar or sugar alcohol may be used in an amount of 10 to 99.99%, preferably 20 to 95%, based on the total weight of the powdery mixture. When the content is less than 10%, sweetness and comfort in the oral cavity are poor.

(3) Medicinal additive

In order to improve the flowability of the powder mixture before filling and the physical properties of the formulation, and also to provide comfort to the patient when taken, another pharmaceutically acceptable additive may be added to the inventive formulation in addition to the pharmaceutically active ingredient and the sugar or sugar alcohol. Examples are a low-melting binder, a dispersant, a lubricant and an excipient (e.g. sweetener, filler).

The low temperature melting binder functions to maintain the hardness and shape of the fast disintegrating agent during handling and storage. The low-temperature-melting binder may be any of conventional binders and has a melting temperature of 100 ℃ or less, and examples thereof include polyethylene glycol, poloxamer, HCO, glycerin, propylene glycol, glycerin ester, derivatives thereof, and mixtures thereof. Among them, preferred are polyethylene glycols 200, 300, 400, 600, 1000, 1500, 2000, 3000, 4000, 6000, 8000 and 20000, poloxamers 188, 237, 338 and 407, HCO-50, HCO-60, glycerol, glyceryl behenate, glyceryl monostearate, glyceryl monooleate, propylene glycol, medium chain triglycerides and fatty acid glycerides.

Disintegrants for faster dispersing formulations in the oral cavity can be selected from the group consisting of: crosslinked polyvinylpyrrolidone, crosslinked carboxymethylcellulose, sodium carboxymethyl starch, calcium carboxymethylcellulose, and mixtures thereof.

The lubricant may be selected from the group consisting of: magnesium stearate, talc, silicon dioxide, sodium stearyl fumarate, valine, sucrose fatty acid esters, hydrogenated castor oil, and mixtures thereof.

As excipients, sweeteners such as aspartame, stevioside, sucralose and acesulfame, or fillers such as microcrystalline cellulose, calcium phosphate, calcium carbonate and starch may be used.

Each 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 mixture.

In the present invention, the pharmaceutically active ingredient, the sugar or sugar alcohol powder, and optionally the pharmaceutically acceptable additives may be mixed according to a conventional dry or wet mixing method. All components were homogeneously mixed in a dry mixing manner in one mixer. The wet mixing method involves forming part or all of the components into a wet granular texture and drying the resulting wet granules.

Subsequently, a packaging material such as a bottom bag film having the function of a bottom packaging mold is filled with a predetermined amount of the thus obtained mixed powder. Suitable packaging materials may be aluminium, PVC or PVDC. In particular, aluminum is preferred, which is subjected to a heating range of 200 to 1000 ℃. In case of using PVC or PVDC, the filled powder alone can be selectively heated, thereby preventing thermal deformation of the packaging material. A bottom pocket film for packaging with a specific character or pattern can be used as an agent for obtaining a marking with such character or pattern. Preferably, after filling, the mixed powder in the packaging material may be compacted with a compaction rod to improve its consistency.

< step (B) >

The packaging material-filled mixture obtained in the present invention is heated to a temperature in the range of 200 to 1000 c for a period of 1 to 60 seconds, preferably 1 to 30 seconds, using radiant heating to cure the filled mixture and obtain the desired fast disintegrating agent. The adhesion of the preparation to the surface of the packaging material can be prevented by adjusting the ratio of the components of the mixed powder and the heating conditions.

In the present invention, the exposure of the mixture to high temperatures for a short period of time reduces thermal decomposition of the active ingredient. The exposure time may depend on the nature of each component used. The heating means may use, for example, a halogen lamp, an infrared heater, and a heating channel, and is preferably a halogen lamp.

The upper cover film can then be placed over and cover the bottom pocket film and form a contoured formulation to complete the shell of the formulation. The upper cover film may be made of aluminum, but is not limited thereto, and it may be any conventional material that allows easy peeling.

The solidified mixture obtained in step (B) may be formulated into tablets, pills, capsules or disintegrators, preferably tablets, according to conventional methods.

As described above, according to the method of the present invention, an oral preparation which produces rapid disintegration in the oral cavity and provides improved comfort when taken by a patient can be prepared in a simple and economical manner, avoiding deterioration of physical properties or undesirable dimensional changes which would be produced when using conventional methods involving any pore-forming step.

The following examples are intended to further illustrate the invention without limiting its scope.

Example 1

Famotidine as an active ingredient in an amount of 20 mg and xylitol as a sugar alcohol in an amount of 300 mg were uniformly mixed, and the mixed powder was filled in a pouch-shaped aluminum film (bottom pouch film). Then, the mixture contained in the bag-like film was heated at about 800 ℃ for 6 seconds using an infrared lamp to complete curing. Then, an aluminum film cover (upper cover film) was placed on the bottom pocket film and sealed to obtain the inventive fast disintegrant tablet.

Example 2

The procedure of example 1 was repeated except that the filled mixture was heated at about 400 ℃ for 20 seconds using an infrared lamp to obtain the inventive rapidly disintegrating tablet.

Example 3

The procedure of example 1 was repeated except that the filled mixture was heated at about 600 ℃ for 15 seconds using an infrared lamp to obtain an inventive rapidly disintegrating tablet.

Example 4

The procedure of example 1 was repeated except that the filled mixture was heated at 400 ℃ for 30 seconds using an infrared lamp to obtain the inventive rapidly disintegrating tablet.

Example 5

The procedure of example 1 was repeated except that the filled mixture was heated at about 1000 ℃ for 2 seconds using an infrared lamp to obtain an inventive rapidly disintegrating tablet.

Examples 6 to 10

The procedure of example 1 was repeated using one of 300 mg of sorbitol, a mixture of 150 mg of xylitol and 150 mg of sorbitol, 300 mg of maltitol, 300 mg of mannitol and 300 mg of erythritol as a sugar alcohol component, instead of 300 mg of xylitol, to obtain respective rapidly disintegrating agent tablets.

Examples 11 to 20

The procedure of example 1 was repeated using 300 mg of one of lactose, glucose, sucrose, fructose, maltose, palatinose (Paratinose), ribulose, maltodextrin, trehalose and dextran as a sugar component, instead of using xylitol as a sugar alcohol component, to obtain respective rapidly disintegrating tablet.

Examples 21 to 45

The procedure of example 1 was repeated using 50 mg tramadol hydrochloride, 50 mg ibuprofen, 30 mg dexibuprofen, 50 mg aspirin, 50 mg celecoxib, 20 mg hydrochloric acidVardenafilOne of 5 mg of amlodipine, 50 mg of cefdinir, 50 mg of teofilin, 4 mg of ondansetron, 50 mg of sildenafil, 5 mg of donepezil, 4 mg of galantamine, 0.2 mg of tamsulosin hydrochloride, 4 mg of sumatriptan, 4 mg of montelukast, 10 mg of loratadine, 2 mg of glimepiride, 30 mg of fexofenadine, 5 mg of tolazamide, 50 mg of topiramate, 2 mg of risperidone, 10 mg of olanzapine, 2.5 mg of zolmitriptan, and 5 mg of montelukast as an active ingredient, instead of 200 mg of famotidine, to obtain respective rapidly disintegrating tablets.

Examples 46 to 51

The procedure of example 1 was repeated except that one of 10 mg of PEG6000, 20 mg of PEG6000, 40 mg of PEG6000, 10 mg of poloxamer 188, 20 mg of poloxamer 188 and 40 mg of poloxamer 188 was further added to the mixed powder as a low-temperature-melting binder to obtain respective rapidly disintegrating agent tablets.

Example 52

The procedure of example 1 was repeated except that 300 mg of mannitol was dissolved in a mixture of 10 mg of water and 10 mg of ethanol, the solution was subjected to wet granulation, and the resulting wet granules were dried and used as sugar alcohol instead of 300 mg of xylitol, to obtain the inventive rapidly disintegrating tablet.

Example 53

The procedure of example 1 was repeated except that 150 mg of xylitol and 150 mg of mannitol were dissolved in a mixture of 5 mg of water and 10 mg of ethanol, the solution was subjected to wet granulation, and the resulting wet granules were dried and used as sugar alcohol instead of 300 mg of xylitol, to obtain the inventive rapidly disintegrating tablet.

Example 54

The procedure of example 1 was repeated except that 50 mg of xylitol and 250 mg of mannitol were dissolved in a mixture of 5 mg of water, 10 mg of ethanol and 5 mg of medium chain triglyceride (MTC oil), the solution was subjected to wet granulation, and the resulting wet granules were dried and used as sugar alcohol instead of 300 mg of xylitol to obtain the inventive rapidly disintegrating agent tablet.

Example 55

The procedure of example 1 was repeated except that 50 mg of xylitol and 250 mg of mannitol were dissolved in a mixture of 5 mg of water, 10 mg of ethanol and 5 mg of medium chain triglyceride (MTC oil), the solution was subjected to wet granulation, and the resulting wet granules were dried and used as sugar alcohol instead of 300 mg of xylitol, and 30 mg of crosslinked PVP as a disintegrant was further added to the mixed powder to obtain the inventive rapidly disintegrating tablet.

Comparative example 1

Gaster brand orally dispersible tablets (containing 20 mg of famotidine) commercially available from Dong-A pharmaceuticals, Inc. were used as the comparator. Gaster brand oral dispersible tablets were prepared using conventional WOWTAB technology.

Test example 1 decomposition test

[ disintegration Rate ]

The disintegration rate (sec) of the tablet was determined according to a basic test disclosed by korean pharmaceutical companies by putting 5 ml of distilled water (in a spoon) at room temperature and then measuring the time for it to completely decompose.

[ disintegration Rate in test tube ]

A90 mm diameter piece of filter paper was placed on a 100X 10 mm petri dish. 7 ml of distilled water was poured on the petri dish and the dish was allowed to tilt to completely wet the filter paper. The disintegration rate (seconds) of the tablet in the test tube was determined by placing it on wet filter paper and then measuring the time it was completely wetted due to capillary phenomenon.

[ disintegration Rate in oral cavity ]

The rate of disintegration of the tablet in the mouth (in seconds) was determined by placing it on the dry tongue of a healthy adult male and then measuring the time it takes for it to completely disintegrate and melt when rubbed.

The disintegration rate and the overall taste of the tablets obtained in examples 1 to 55 and comparative example 1 were determined as described above. The results are shown in Table 1.

TABLE 1

As shown in Table 1It can be seen that the inventive tablets obtained in the examples completely disintegrated in the oral cavity in a time of 2 to 33 seconds, while the resulting delay had a satisfactory taste for oral administration. In comparison, Gaster of comparative example 1^TMOral dispersible tablets require more than 40 seconds to completely disintegrate in the mouth.

Thus, a packaging machine for preparing a rapid disintegrating agent in a mass production manner using the preparation method of the present invention will be described in detail.

The blister pack machine is a typical pharmaceutical pack machine. The term blister pack means a packing method in which a container-shaped portion is formed on a flat film made of a composite or metal, the container-shaped portion is filled into an object, the container-shaped portion is covered with a lid sealed by an adhesive, and is drawn to a predetermined size and cut, thus forming a unit for packing the object. Originally, this bubble-packing method was developed in pharmaceutical companies and used to pack tablets or capsules in packages. The current bubble packaging method is widely used in the confectionery production or in the manufacturing process of cosmetics or household goods. Unlike other packaging methods, in the bubble wrapping method, since a transparent film is used, the product is easily observed, and since the product is wrapped with a film, the shape of the product wrapped with a film can be easily changed by changing the shape of a forming die having, for example, a shape corresponding to the product or other various shapes. Furthermore, the product can be reliably protected due to the use of the hard film. In addition, when it is desired to use the product, anyone can use the product because it is easy to open the product. Moreover, it has the advantage of being very portable.

Such a typical pharmaceutical packaging machine has the following components:

(1) and a film feeding unit for feeding a flat formed film for manufacturing a bottom bag film for packaging. The film feeding unit comprises an unwinder from which the formed film is removed and carried, and a removing tool which removes the formed film from the unwinder at a constant speed.

(2) A film forming unit including a mold having a shape corresponding to a desired shape of a product, which is operated by placing a formed film on the mold, and pressing the formed film by moving a pressing rod downward, thus forming a pressed pocket on the formed film. The film forming unit may include a preheating section that preheats the formed film to improve the plasticity of the film.

(3) And a contents input unit having a hopper in which the contents are contained and inputting the contents into the film pocket.

(4) And a sealing unit for sealing the upper cover film on the bottom pouch film into which the contents are put. The packaging unit comprises an unwinder on which a cover film is wound in a roll shape, and a sealing device.

(5) And the cutting unit is used for cutting the product into the packaging unit. The cutting unit may contain embossing devices to indicate a product number or production date, a slitting device to form perforation lines and an impact device to perform the impact operation, as required.

(6) And a control unit installed on a front surface of the machine. The control unit controls the operation of the machine in accordance with the manipulation instruction of the worker. The control unit may be implemented by a control board, for example.

The operation of the pharmaceutical packaging machine having the above-described construction will be described below. The formed film wound on the unwinder of the film feeding unit is conveyed at a certain speed and preheated by the preheating part of the film forming unit at a certain temperature suitable for forming. The formed film is then immediately compressed by a compression bar so that pockets with contents therein are formed in the formed film. Each pocket has the shape of the container. In this manner, the formed film with pockets becomes the bottom pocket film for packaging. Then, the contents (e.g., pills) are filled into the respective pockets by the contents input unit. The bottom pouch film, in which the contents are contained, is sent to a sealing unit and is combined with the upper cover film by pressing, thereby sealing the contents. Subsequently, it is cut into packaging units by a cutting unit.

In principle, the pharmaceutical packaging machine according to the invention has the above-described construction and operation, but its specific shape and function are not limited. In other words, any packaging machine can be used in the method of the present invention as long as it has a basic blister packaging function.

Fig. 1 shows a block diagram of a construction of a packaging machine for preparing a fast disintegrant for oral administration according to an embodiment of the present invention. Fig. 2 is a cross-sectional view of the pharmaceutical material delivery unit 130 of the packaging machine.

The packing machine 100 for preparing a fast disintegrant for oral administration according to the present invention has a film feeding unit 110, a film forming unit 120, a sealing unit 170, a cutting unit 180, and a control unit 190 as essential components, similar to a typical pharmaceutical packing machine. However, the packing machine 100 further includes a drug material-carrying unit 130 which inputs the powdered mixture 20 or the tablets 22, which are made by pressing the powdered mixture 20 to form a predetermined shape, into the pockets 10a of the bottom pouch film 10, unlike a typical pharmaceutical packing machine having a content-inputting unit. In addition, the packing machine 100 further includes a heating unit 160 that heats the mixture or tablets put into the bottom pouch film 10 to melt and fuse the mixture or tablets.

Accordingly, the film feeding unit 110, the film forming unit 120, the pharmaceutical raw material conveying unit 130, the heating unit 160, the sealing unit 170, and the cutting unit 180 are arranged in order of location.

The pharmaceutical raw material carrying heater 130 inputs the powdered mixture 20, which is obtained by mixing the pharmaceutically active ingredient with sugar or sugar alcohol powder, or the tablet 22, which is manufactured by pressing the powdered mixture 20 into the pocket 10a formed on the bottom pocket film 10.

For example, in the drug material delivery unit 130, an appropriate amount of the powdery mixture 20 is put into a hole of the powder pressing position and pressed, thus forming the tablet 22 of a predetermined shape. Subsequently, the tablets 22 are put into the pockets 10a of the bottom bag film 10, which are previously placed at positions corresponding to the discharge positions of the medicinal materials.

In this embodiment, the drug material delivery unit 130 includes a filling tray 132 having at least two filling holes 132a, which are alternately arranged between the powder pressing position and the drug material discharge position. The powdered mixture 20 is deposited on the upper surface of the fill pan 132. The drug material conveying unit 130 further includes a bottom plate 134 which is disposed below the filling plate 132 and has an opening 134a which opens to the filling hole 132a and is disposed at the drug material discharge position, while the filling hole 132a disposed at the powder pressing position is closed by the bottom plate 134. The pharmaceutical material delivery unit 130 further includes a pressing bar 136 provided on each filling hole 132a such that the pressing bar 136 moves downward into the corresponding filling hole 132a while pressing the powdery mixture 20 or discharging the tablets 22, and then moves upward, and includes a hopper 138 which transfers the powdery mixture 20 onto the filling tray 132.

Here, the filling tray 132 is a circular tray. At least two filling holes 132a are formed through the filling tray 132 at positions spaced apart from each other at regular angles. The filling hole 132a is moved by the rotation of the filling disk 132, and thus is alternately placed at the powder pressing position and the drug material discharge position.

Therefore, after the powdery mixture 20 is transferred from the hopper 138 onto the filling tray 132, when the filling tray 132 is rotated and the filling holes 132a are thus moved toward the powder pressing position and the pharmaceutical-material discharge position, respectively, some of the accumulated powdery mixture 20 is naturally sucked into the corresponding filling holes 132 a. The filling tray 132 is stopped when the filling hole 132a reaches the powder pressing position. Next, the corresponding pressing rod 136 is moved into the filling hole 132a to press the powdery mixture 20 into the filling hole 132a, so that the tablet 22 is formed with a satisfactory integration force. Subsequently, the pressing rod 136 is moved upward, and the filling tray 132 is rotated at a predetermined angle, so that the filling hole 132a is positioned at the medicine material discharge position. Next, the corresponding pressing rod 136 is moved downward into the filling hole 132a, thus discharging the tablet 22 downward out of the filling hole 132 a. The discharged tablet 22 falls into the pocket 10a of the bottom bag film 10, which is previously placed at the medicine material discharge position.

Of course, since all the pressing rods 136 move up and down at the same time, the powder pressing operation and the tablet discharging operation are performed at the same time.

In general terms, the operation of the pharmaceutical material delivery unit 130 includes a step of filling the powdered mixture 20 into the corresponding filling hole, a step of pressing the filled powdered mixture 20, and a step of discharging the tablet 22.

Here, each of the filling step and the pressing step is performed two or more times in order to fix the content of the tablet 22 to an appropriate level. To this end, the number of the filling holes 132a and the number of the pressing bars 136 may be increased as needed. In this case, the rotation step of the filling tray 132 is further subdivided.

Of course, when the number of filling and compression steps is further taken into account, the number of steps may be reduced if the required amount of active ingredient of a target product, i.e. a fast disintegrant, is relatively small, or if the density of the active ingredient is relatively high.

Meanwhile, when one tablet 22 is formed at the powder pressing position, when the formed tablet 22 is moved from the powder pressing position to the drug material discharge position, or when the tablet 22 is placed at the drug material discharge position, some of the powdery mixture 20, which is around the filling hole 132a in which the tablet 22 is contained, must be prevented from unexpectedly entering the filling hole 132a in order to improve the marketability of the tablet 22 and the sealing property between the upper cover film and the bottom pouch film 10. To achieve the above object, as shown in fig. 3, a powder blocking means 137, extending from a position in front of the powder pressing position to a position behind the medicine material discharge position, may be placed on the upper surface of the filling tray 132. The powder blocking tool 137 may have a plate-like shape.

In the figure, reference numeral 112 denotes a guide block which guides the movement of the bottom pouch film 10, and reference numeral 139 denotes a leakage preventing piece which prevents the powdery mixture 20 on the filling tray 132 from being unexpectedly separated from the filling tray 132.

Although the machine of the present invention is illustrated as being configured such that the powdered mixture 20 is formed into a tablet and then fed into the bottom pouch film 10, it may be configured such that the powdered mixture 20 is fed directly into the bottom pouch film 10.

Meanwhile, the heating member 160 heats the mixture or tablet input into the bottom pouch film 10 at a temperature ranging from 200 to 1000 degrees for a relatively short time ranging from several seconds to several tens of seconds, thus melting and fusing the mixture or tablet while reducing decomposition of one pharmaceutically active ingredient. In the case of a powdered mixture, the powdered mixture is melted and fused, thus forming a fused tablet shape. In the case of tablets, the fusion force can be further enhanced.

FIG. 4 shows a schematic diagram of one representative example structure of the heating unit 160;

the heating unit 160 includes a heat generator 162 disposed on the bottom pouch film 10 disposed on the guide block 112 so as to be movable. The heat generator 162 heats the mixture or tablet filled in the bottom pouch film 10, thus melting and fusing the mixture or tablet. The heating unit 160 further includes a barrier 164, which is reciprocally inserted into a space between the heat generator 162 and the bottom pouch film 10 to allow or block heat from being conducted from the heat generator 162 to the mixture or tablet, thus controlling the time the mixture or tablet is exposed to heat and enabling the heating operation to be repeatedly performed.

Here, a halogen lamp, an infrared lamp or the like, which can heat an object at a temperature of 200 degrees or more, may be used as the heat generator 162. Several lamps may be used as the heat generator 162 if necessary.

In addition, a plate, which can cover the bottom pouch film 10 and block heat from being conducted from the heat generator 162 to the bottom pouch film 10, may be used as the barrier 164. The time for which the bottom pouch film 10 is exposed to the heat source by the retraction of the shutter 164 may vary depending on the kind of the components in the drug material or the kind of the material used for the bottom pouch film 10.

The opening and closing of the shutter 164 is repeated while the bottom pouch film 10 is advanced, so that the mixture or tablet in the bottom pouch film 10 is heated for a predetermined exposure time. This operation may be performed repeatedly and continuously.

Meanwhile, as shown in fig. 5, the packing machine 100 for preparing a fast disintegrant for oral administration according to the present invention may further comprise a compressing unit 140 between the drug material-carrying unit 130 and the heating unit 160. The compressing unit 140 serves to compress the mixture or the tablet, which is input into the corresponding pocket 10a of the bottom pouch film 10 through the drug material-carrying unit 130, thus forming the tablet 22 having a shape corresponding to the pocket 10 a.

As shown in fig. 6, the pressing unit 140 includes a pressing rod 142 which moves downward into the pocket 10a of the corresponding bottom pocket film 10 to press the mixture or tablet and then moves upward.

Here, in order to compress the mixture or tablet in multiple steps and thus form a mixture or tablet more similar to the shape of the corresponding pocket 10a, several compression rods having different shapes may be placed at the front and rear positions to compress the mixture or tablet. In the figures, the compaction bar 142 is illustrated as comprising a first compaction bar that primarily compacts a peripheral portion of the mixture or tablet and a second compaction bar that secondarily compacts a central portion of the mixture or tablet.

In addition, each of the compression rods 142 can be rotated at a fine angle while the corresponding mixture or tablet filled in the bag-shaped film is in a compressed state. Therefore, the mixture or the tablet can be formed to have a uniform shape in the pocket 10a without causing the shape to be broken or to be inclined to one side.

Meanwhile, as shown in fig. 7, the packing machine 100 for preparing a fast disintegrant for oral administration according to the present invention further comprises a pumping unit 150 interposed between the drug material delivery unit 130 and the heating unit 160. The suction unit 150 generates suction pressure on the bottom pouch film 10 filled with the mixture or the tablet therein, thus drawing and removing unnecessary fine powder from the bottom pouch film 10, thereby improving the marketability of the product and the sealing performance between the upper cover film and the bottom pouch film 10.

As shown in fig. 8, the suction unit 150 includes a suction nozzle 152 connected to a vacuum facility line of a factory or a vacuum pump to generate a vacuum suction pressure on the bottom pouch film 10, and a screen 154 disposed at a position between the suction nozzle 152 and the bottom pouch film 10 to prevent the mixture or tablet filled in the bottom pouch film 10 from being sucked upward by the vacuum suction pressure.

Here, the suction nozzle 152 can be moved downward or upward so that it is adjacent to or removed from the bottom pocket film 10.

The general operation of the packing machine 100 for preparing a fast disintegrant for oral administration having the above-mentioned construction according to the present invention will be described as follows.

First, a formed film is fed at a constant speed from the film feeding unit 110. The formed film is preheated and pressed by the film forming member 120, so that the pocket 10a having a container shape is formed on the formed film, thereby forming the bottom pocket film 10.

Subsequently, the powdery mixture or tablets are put into the respective pockets 10a of the formed bottom pocket film 10 by the drug material delivery unit 130. The mixture or tablets filled in the inlet bag film are compressed in the corresponding pockets 10a of the bottom bag film 10 by the compressing unit 140, thus forming the tablets 22 having a shape corresponding to the shape of the pockets 10 a.

Subsequently, the unnecessary fine powder on the bottom pouch film 10 is removed by the vacuum pressure of the suction unit 150.

The mixture or the tablets in the bottom pouch film 10 are thereafter heated by the heating unit 160, so that each mixture or tablet is melted and fused to secure a certain firm bonding force, thereby being formed into a fast disintegrating agent for oral administration.

Then, the bottom pouch film 10 containing the fast orally disintegrating dosage form is thus sealed by being pressed onto the upper cover film by the sealing unit 170, thereby completing the packaging operation. Subsequently, the product is cut into predetermined packing units by the cutting unit 180.

Finally, the packaged fast disintegrant product for oral administration is slowly cooled in a packaged state at room temperature.

Thus, the rapid disintegrant for oral administration can be conveniently and economically prepared by a single production line using a mass production method.

In the present invention, although the heat treatment is illustrated as being performed using the heating unit 160 as an intermediate step of the packaging process, the heat treatment may be performed after the process of attaching the upper cover film to the bottom pocket film is completed, i.e., after the packaging process is completed. For this reason, after the packaging process of the rapidly disintegrating agent product is completed, the product may be placed in a heating chamber so that the product is heated individually.

While the invention has been described with reference to the above specific embodiments, it will be understood that various changes and modifications in the practice of the invention, which may occur to those skilled in the art, are also within the scope of the invention as defined by the appended claims.

Claims (16)

1. A packaging machine for preparing a fast disintegrating formulation for oral administration comprising:

a film conveying unit for conveying the formed film;

a film forming unit for forming the formed film to form a bottom pocket film provided with a container-shaped pocket;

a drug material delivery unit to fill or input a powdery mixture or a tablet formed by pressing the powdery mixture into a predetermined shape into a pocket of the bottom pocket film;

a heating unit to heat the filled mixture or tablet to melt and combine the filled mixture or tablet; and

and a sealing unit for attaching an upper cover film to the bottom pouch film.

2. The packaging machine of claim 1, further comprising:

a cutting unit to cut a packaging material, which is formed by attaching the upper cover film to the bottom pocket film, into predetermined units; and

and the control unit is used for operation control.

3. The packaging machine according to claim 1, wherein the powdery mixture contains a pharmaceutically active ingredient and a sugar or sugar alcohol powder.

4. The packaging machine of claim 2, wherein the powdered mixture further comprises a pharmaceutically acceptable additive selected from the group consisting of: low temperature melting binder, disintegrant, lubricant, excipient, and mixtures thereof.

5. The packaging machine of claim 1 wherein the pharmaceutical material delivery unit comprises:

a packing tray having at least two packing holes which are separately and replaceably disposed at a powder pressing position and a drug material discharge position, the packing tray allowing the powdery mixture to be stacked on an upper surface thereof;

a bottom tray provided below the filling tray for opening the filling hole provided at the medicine material discharge position and closing the filling hole provided at the powder pressing position;

a pressing bar located above each filling hole, the pressing bar simultaneously moving downward into the corresponding filling hole to press the powdery mixture filled in the filling hole of the powder pressing position and discharge the tablets in the filling hole of the drug material discharge position; and

a hopper for conveying the powdered mixture onto the filling tray.

6. A packaging machine according to claim 5 wherein the filling disc is rotated and the accumulated powdered mixture is conveyed into the respective filling aperture during rotation of the filling disc.

7. A packaging machine according to claim 5 wherein the powder compaction stations comprise at least two powder compaction stations so that the transport and compaction of the powdered mixture is performed in multiple steps.

8. The packaging machine of claim 5 wherein the pharmaceutical material delivery unit further comprises:

powder blocking means provided on said filling disc for blocking additional powdered mixture from entering said filling aperture, a powder blocking plate extending from a position in front of said powder compaction position to a position behind said drug substance discharge position.

9. The packaging machine of claim 1 wherein the heating unit comprises:

a heat generator for heating the mixture or tablets filled in the bottom pouch film; and

a baffle for telescopically inserting into the space between the heat generator and the bottom pocket film to control the time period for which the mixture or tablet is heated.

10. A packaging machine according to claim 9 wherein the heat generator comprises a halogen lamp or an infrared lamp.

11. The packaging machine of claim 1, further comprising:

a compressing unit for compressing a mixture or tablet, which is input into the pocket of the bottom pocket film by the drug material conveying unit, thereby forming the mixture or tablet into a shape corresponding to the shape of the pocket.

12. The packaging machine of claim 11 wherein the pressing unit comprises:

a compaction rod to move down into the pocket of the bottom pocket film and up after compressing the mixture or tablet.

13. The packaging machine of claim 12 wherein the compaction bars of the compaction unit comprise at least two compaction bars arranged in series to continuously compact the mixture or tablet at least two times.

14. The packing machine as claimed in claim 13, wherein each of the compaction bars of the compaction unit is rotated after being moved down into the pocket of the bottom pocket film to compact the mixture or tablet filled in the pocket, so that the mixture or tablet is uniformly formed in the pocket.

15. A packaging machine according to claim 1 or 11, further comprising:

a suction unit for generating suction pressure on the bottom pocket membrane to thereby draw and remove unwanted fine powder from the bottom pocket membrane.

16. The packaging machine of claim 15 wherein the suction unit comprises:

a suction nozzle for generating a vacuum suction pressure on the bottom pocket film; and

a barrier positioned between the suction nozzle and the bottom pouch film to prevent the mixture or tablet filled in the pouch film from being sucked upward by the vacuum suction pressure.