CN102424151B - Apparatus for preparing rapidly disintegrating formulation for oral administration - Google Patents
Apparatus for preparing rapidly disintegrating formulation for oral administration Download PDFInfo
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- CN102424151B CN102424151B CN201110233231.3A CN201110233231A CN102424151B CN 102424151 B CN102424151 B CN 102424151B CN 201110233231 A CN201110233231 A CN 201110233231A CN 102424151 B CN102424151 B CN 102424151B
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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
The application requires the preceence of the korean patent application No.10-2007-0063757 of submission on June 27th, 2007; The application is dividing an application of the Chinese patent application No.200880022469.8 that submits on December 28th, 2009.
technical field
The present invention relates to a kind of method and wrapping machine of preparing quickly disintegrated peroral dosage form in oral cavity, and the fast disintegrant of preparing according to this.
background technology
Fast disintegrant is normally prepared by the distinct methods that uses raw material, the humidification of desivac, disintegrant, distillation sample or dry.
For example, the patent No. is that 5631023 and 5976577 US Patent discloses the preparation that a kind of solution experience freeze-drying that makes to contain medicine by use obtains.This preparation recently for the preparation of Merck, GlaxoWelcome and Schering-Plough company respectively with Pepcid RPD(famotidine preparation), Zofran zydis(ondansetron preparation) and the commercially available product of Claritin RediTabs trade mark.These preparations 2-3 in oral cavity is disintegratable in second, but prepare in their process, needs to use special equipment and packing, causes yield reducation and high manufacturing cost.
In order to address this problem, publication number be the international monopoly of WO99/47126 proposed a kind of for, by active component and the compression of water soluble (CO) polymers adhesive agent are formed to tablet, and the tablet obtaining is carried out under high damp condition to humidifying, be then dried to prepare the method that does not contain the preparation of residual organic solvents.This method is as the WOWTAB technology of Japanese Yamanouchi drugmaker exploitation and by known to everybody.In addition, the International Patent Publication that publication number is WO93/12769 a kind of for by place the suspending fluid contain active component, agar and sugar at mould, then under 30 ℃, 760mmHg pressure, dry this suspending fluid is prepared the method for formulation.But this method bring low efficiency and product design inhomogeneous.
Alternately, the Orasolv technology of preparing fast disintegrant is by Cima development in laboratory and number be open in 5178878 and 6024981 US Patent.Commercially available prod mark Zimig Rapimelt (a kind of Zomitriptan formulation) trade mark being obtained by Orasolv technology, by Astrazeneka company, introduced to the market, but it does not produce gratifying mouthful in disintegration effect, and because produce the gas that bubbles when taking to a kind of uncomfortable sensation of people.
It is a kind of for by mixed active excipient for example urethane, urea, ammonium carbonate and naphthalene and other tablet ingredients that the patent No. is that 3885026 US Patent discloses, and compressed mixture forms tablet, heats tablet and removes the method that active excipient is prepared porous tablet.
Further, U.S. Patent number 4134943 has been described a kind of for have molten solvent (water, cyclohexane, benzene, three generations's butanols) and tablet ingredients between-30 ℃ to 25 ℃ by mixing, cooling mixture is to solidify described solvent, compress this solid mixture to form tablet, then by evaporation, therefrom remove the method that solvent is prepared porous tablet, but such porous tablet is due to remaining excipient or organic solvent and may be toxic.
As mentioned above, traditional fast disintegrant by form a kind of comprise can be by purifying, the tablet of evaporation or the dehumidifying special material that remove, then therefrom remove corresponding special material and prepare, their porous that becomes like this, and allow the quick infiltration of saliva.But this conventional dosage forms has the pore of any formation, cause the deterioration of significant physical property or less desirable size to change.
Therefore, be necessary to develop fast disintegrant, it can easily be produced and for patient provides comfortable sensation when taking, and does not cause the problem that above-mentioned orthodox method produces.
Summary of the invention
Therefore, an object of this invention is to provide a kind of simple method and wrapping machine for the preparation of oral formulations, and this oral formulations produces fast decoupled and when taking, provides the comfort level of improvement for patient in oral cavity.
According to one aspect of the present invention, a kind of method for the preparation of oral fast disintegrant is provided, comprise: (A) medicine activity component and sugar or sugar alcohol powder are mixed to get to pulverulent mixture, and pulverulent mixture is packed in packing; And (B) heating in step (A), obtain pack compound in packing into solidify this compound.
According to another aspect of the present invention, provide a kind of by said method, prepared for oral fast disintegrant.
Still according to another aspect of the present invention, provide a kind of wrapping machine for the preparation of oral fast disintegrant, comprised: film supply unit is in order to have carried the film forming; Film forming unit is in order to the film of this formation of moulding, thereby formed a bottom pockets film (lower pocket film), is designed with the pocket of container shapes; Medicine material supply unit is with filling pulverulent mixture or tablet to the bag of this bottom pockets film, and it makes it have predetermined shape and form by suppressing this pulverulent mixture; Compound or tablet that heating unit is loaded in order to heating, therefore melt and in conjunction with compound or the tablet of this filling; And a sealing unit is in order to be attached to top coverlay (upper cover film) on bottom pockets film.
According to the present invention, the oral formulations that a kind of comfort level when producing quick disintegration and considering that patient takes in oral cavity is improved, it can be prepared in simple and economical mode by a single processing route, and avoids the deterioration of caused expection physical property when using a kind of orthodox method that contains any hole formation step or produce less desirable change in size.
Accompanying drawing explanation
Above and other object of the present invention, characteristics and advantages will obtain understanding more clearly in the detailed description together with appended diagram below, wherein:
Fig. 1 shows the block diagram according to the wrapping machine for the preparation of oral fast disintegrant of embodiment of the present invention;
Fig. 2 is the cross sectional drawing according to the medicine material supply unit of the wrapping machine for the preparation of oral fast disintegrant of the present invention;
Fig. 3 shows the multiview drawing according to a key component of the medicine material supply unit of the wrapping machine for the preparation of oral fast disintegrant of the present invention;
Fig. 4 is the cross sectional drawing according to the heating unit of the wrapping machine for the preparation of oral fast disintegrant of the present invention;
Fig. 5 shows the block scheme according to the wrapping machine structure for the preparation of oral fast disintegrant of another embodiment of the present invention;
Fig. 6 is the cross sectional drawing according to the press unit of the wrapping machine for the preparation of oral fast disintegrant of embodiment in Fig. 5;
Fig. 7 is the block scheme according to the wrapping machine structure for the preparation of fast disintegrant of another embodiment of the present invention;
Fig. 8 is the cross sectional drawing according to the pump unit of the wrapping machine for the preparation of oral fast disintegrant of Fig. 7 embodiment.
The specific embodiment
Below this invention is described in detail.
The feature of inventive method is active constituents of medicine and sugar or the compound with the sugar alcohol of a lot of inherent pores to melt combination, by loading compound (steps A) and heating (step B) in packing, form a kind of fast disintegrant with inherent pore, it is different from by purifying, evaporation or be dried and at random produce the orthodox method of pore.
The method of this invention can not cause the deterioration of preparation physical property or less desirable size to change, and it is very simple and cheap.
< step (A) >
A kind of composite for the preparation of invention preparation (mixed-powder), it comprises active constituents of medicine and sugar or sugar alcohol, and said composition can further comprise a kind of pharmaceutically acceptable additive.
Thus, the composition that is used for a kind of invention composite of rapid dispersion preparation is described in detail as follows: be selected from lower group: Tamsulosin, sumatriptan, zolmitriptan, rizatriptan, Loratadine, fexofenadine, Glimepiride, TORA, frusemide, Gabapentin, lyrica, valproate, Topiramate, carbamazepine, Lamotrigine, Oxcarbazepine, selegiline, Risperidone, Ziprasidone, Quetiapine, Olanzapine, Clozapine, Paliperidone, pharmaceutically acceptable salt and its compound.
(1) medicine activity component
1. antipyretic, analgestic or antiinflammatory, for example C16H25NO2, brufen, Dexibuprofen, aspirin, paracetamol, Indomethacin, C14H10Cl2NNaO2, Ketoprofen, isopropylantipyrine, phenacetin, Fluprofen, phenylbutazone, Etodolac, Sai-Mi-Xi-Bu, etoricoxib and its pharmaceutically acceptable salt class.
2. anti-gastric-ulcer preparation, for example Cimetidine, famotidine, ranitidine, nizatidine, Roxatidine and its pharmaceutically acceptable salt class.
3. cardiovascalar agent or vasodilation medicament, for example nifedipine, Amlodipine, Verapamil, captopril, diltiazem hydrochloride, Propranolol, oxprenolol, monobel, enalapril and its pharmaceutically acceptable salt class.
4. microbiotic, for example aminobenzylpenicillin, Amoxicillin, cefalexin, cefuroxime, Cefdinir, cefadroxil, Cefprozil, Cefpodoxime, Cefditoren, Cefaclor, Cefixime, Cefradine, Loracarbef, ceftibuten, cefatrizine, Cefcarpen, erythromycin series, Tetracyclines, quinolones and its pharmaceutically acceptable salt class.
5. pectoral or antiasthmatic, for example theophylline, aminopyrine, codeine, phosphate, hydrochloric acid methylephedrine, dextromethorphan, coscopin, salbutamol, Ambroxol, clenbuterol, Terbutaline, montelukast and its pharmaceutically acceptable salt class.
6. antiemetic or stomach function regulator, for example Ondansetron, Metoclopramide, domperidone, Trimebutine Maleate, Cisapride, levosulpiride and its pharmaceutically acceptable salt class.
7. treat impotence medicament, for example silaenafil, Vardenafil, Tadalafei, udenafil and its pharmaceutically acceptable salt class.
8. treat dementia drug, for example donepezil, galanthamine, Rivastigmine, acetyl group Carnitine, Memantine, Zaliprodene and its pharmaceutically acceptable salt class.
Except mentioned component, other active component can comprise a kind of for example Tamsulosin of benign prostatic hyperplasis medicament for the treatment of; A kind for the treatment of cycle migraines medicament is sumatriptan, zolmitriptan and rizatriptan for example; A kind of incitantia; A kind of antibiotic medicament; A kind of antihistaminic is Loratadine and fexofenadine for example; A kind of oral antidiabetic agent is Glimepiride for example; A kind of anti-allergic agent; A kind of contraceptive; A kind of vitamin; A kind of anticoagulant; A kind of muscle relaxant; A kind of cerebrum metabolism improver; A kind of antidiuretic is TORA and frusemide for example; A kind of antispasmodic agent for example adds Gabapentin, lyrica, valproate, Topiramate, carbamazepine, Lamotrigine, Oxcarbazepine; A kind for the treatment of of Parkinson disease agent is selegiline for example; A kind of schizophrenia is Risperidone, Ziprasidone, Quetiapine, Olanzapine, Clozapine and Paliperidone for example; With and pharmaceutically acceptable salt class; With a kind of biovaccine.
The adoptable amount of active component is counted 0.01-90% by pulverulent mixture total weight, is preferably 0.02 to 70%.
(2) sugar or sugar alcohol
Sugar or sugar alcohol play the effect that keeps preparation shape, determine its dissolution rate, and sweet taste is provided, solubility and the comfort in oral cavity.Therefore preferably sugar or sugar alcohol are sweet in water-soluble.Its representative illustration comprises lactose, glucose, sucrose, fructose, sweet mellow wine, D-sorbite, xylitol, erythritol, ribulose, maltitol, maltose, maltodextrin, palatinose (Paratinose), trehalose, glucan and a kind of its compound.
The adoptable amount of sugar or sugar alcohol counts 10 to 99.99% by pulverulent mixture total weight, and preferably 20 to 95%.When content is less than 10%, sweet taste and comfort in oral cavity are poor.
(3) medical additive
For improve mixture of powders before filling flowing power and the physical property of preparation, also for when taking for patient provides comfort, except active constituents of medicine and sugar or sugar alcohol, another kind of pharmaceutically acceptable additive can join in invention preparation.It is exemplified as a kind of low temperature and melts adhesive agent, a kind of dispersing agent, a kind of lubricant and a kind of excipient (for example sweetener, extending agent).
The effect that low temperature melts adhesive agent is to keep hardness and the shape of fast disintegrant when processing and store.Low temperature melts adhesive agent can be any in conventional binders and have one 100 ℃ or lower thaw temperature, and its example comprises carbowax, poloxamer, HCO, glycerine, propylene glycol, glycerin ester, its its derivant and its compound.Preferably poly-diethanol 200,300,400,600,1000,1500,2000,3000,4000,6000,8000 and 20000, PLURONICS F87,237,338 and 407, HCO-50, HCO-60, glycerine, glycerine behenate, glyceryl monostearate, glycerine monooleate, propylene glycol, medium chain triglyceride and fatty glyceride among them.
Be used in oral cavity the more disintegrant of rapid dispersion preparation and can be selected from lower group: crosslinked polyvinylpyrrolidone, crosslinked carboxymethyl cellulose, sodium carboxymethyl starch, calcium carboxymethylcellulose and its compound.
Lubricant can be selected from lower group: dolomol, talcum, silicon dioxide, sodium stearyl fumarate, valine, sucrose fatty ester, rilanit special and its compound.
As excipient, can select sweetener for example Aspartame, stevioside, Sucralose and acesulfame, or extending agent for example microcrystalline cellulose, calcium phosphate, calcium carbonate and starch.
By mixture weight, be 100 parts, the amount that every kind of additive can be used is 0.01 to 50 weight portion, is preferably 0.1 to 30 weight portion.
In the present invention, active constituents of medicine, sugar or sugar alcohol powder, and selectable pharmaceutically acceptable additive can mix according to conventional dry or wet-mixing method.All components evenly mixes in dry mixed mode in a mixer.Wet-mixing mode comprises the wet particle of part or all of component being made to wet grain structure dry gained.
Subsequently, a kind of packing, for example, insert the mixed-powder so obtaining of scheduled volume in the bottom pockets film that has a bottom packaged die effect.Suitable packing can be aluminium, PVC or PVDC.Especially, be preferably aluminium, its heated perimeter bearing is 200 to 1000 ℃.In the situation that using PVC or PVDC, the powder of filling is selectively heated separately, prevents thus the thermal deformation of packing.With the packing of a special character or pattern, with bottom pockets film, can be used as obtaining and take the preparation that this character or pattern be mark.Preferably, after filling, the mixed-powder in packing can be compacted to improve its conformability with a kind of compacting rod.
< step (B) >
The compound of inserting packing obtaining be in the present invention heated to range of temperatures be 200 to 1000 ℃ through time of 1 to 60 second, be preferably 1 to 30 second, use the compound that radiation heating is filled to solidify also to obtain desirable fast disintegrant.By adjusting mixed-powder component ratio and heating condition, can prevent the adhesion of preparation and package material surface.
In the present invention, compound is exposed to high temperature through the very short time, has reduced the thermolysis of active component.Open-assembly time can be depending on the character of every kind of component used.Heating arrangement can be used for example halide torch, infrared heater and heat tunnel, preferably halide torch.
Then, top cover film can be placed and covered on bottom pockets film and form the preparation of certain profile, to complete the dress shell of preparation.Top cover film can be made of aluminum, but be not limited to this, and it can be any one traditional material that can allow light peeling.
According to orthodox method, in step (B), the curing mixture of gained can be made tablet, pill, capsule or disintegrant, preferred tablet.
As described above, according to method of the present invention, a kind of in oral cavity, produce quick disintegration and when patient takes, provide the oral formulations of the traveling comfort of improvement can be a kind of the preparation of simple and economical method, avoid relating in use deterioration or the less desirable change in size of the physical property producing when any pore forms the orthodox method of step.
The following examples are for further illustrating the present invention rather than limiting its scope.
Embodiment 1
The famotidine of 20 milligrams is evenly mixed as sugar alcohol as the xylitol of active component and 300 milligrams, and mixed-powder is received in (bottom pockets film) in bag-shaped aluminium film.Then, the compound being contained in bag-shaped film is used infrared lamp curing to complete 6 seconds in about 800 ℃ of heating.Then, aluminium film cover (top cover film) is placed on bottom pockets film and sealing, the fast disintegrant tablet of being invented to obtain.
Embodiment 2
Repeat the step of example 1, except the compound of loading is used infrared lamp, about 400 ℃, heat 20 seconds to obtain the fast disintegrant tablet of being invented greatly.
Embodiment 3
Repeat the step of example 1, except the compound of loading is used infrared lamp, at about 600 ℃, heat 15 seconds to obtain a fast disintegrant tablet of being invented.
Embodiment 4
Repeat the step of example 1, except the compound of loading is used infrared lamp at 400 ℃ of heating 30 seconds, the fast disintegrant tablet of being invented to obtain.
Embodiment 5
Repeat the step of example 1, except the compound of loading is used infrared lamp, at about 1000 ℃, heated for 2 seconds, to obtain a fast disintegrant tablet of being invented.
Embodiment 6 to 10
Repeat the step of example 1, use one of the compound of 300 milligrams of D-sorbites, 150 milligrams of xylitols and 150 milligrams of D-sorbites, the maltitol of 300 milligrams, the sweet mellow wine of 300 milligrams and erythritol of 300 milligrams as sugar alcohol composition, rather than 300 milligrams of xylitols, to obtain fast disintegrant tablet separately.
Embodiment 11 to 20
Repeat the step of example 1, use one of 300 milligrams of lactose, glucose, sucrose, fructose, maltose, palatinose (Paratinose), ribulose, maltodextrin, trehalose and glucan as a kind of composition of sugar, rather than use xylitol as sugar alcohol composition, to obtain fast disintegrant tablet separately.
Embodiment 21 to 45
Repeat the step of embodiment 1, use 50 milligrams of tramadol hydrochlorides, 50 milligrams of brufens, 30 milligrams of Dexibuprofens, 50 milligrams of aspirin, 50 milligrams of Sai-Mi-Xi-Bus, 20 milligrams of hydrochloric acid
vardenafil, 5 milligrams of Amlodipines, 50 milligrams of Cefdinirs, 50 milligrams of teofilin, 4 milligrams of Ondansetrons, 50 milligrams of silaenafils, 5 milligrams of donepezils, 4 milligrams of galanthamines, 0.2 milligram of smooth rope Loews of hydrochloric acid, 4 milligrams of sumatriptans, 4 milligrams of montelukasts, 10 milligrams of Loratadines, 2 milligrams of Glimepirides, 30 milligrams of fexofenadines, 5 milligrams of TORAs, 50 milligrams of Topiramates, 2 milligrams of Risperidones, 10 milligrams of Olanzapines, 2.5 milligrams of zolmitriptans, with the composition of one of 5 milligrams of montelukasts as a kind of active component, rather than 200 milligrams of famotidines, to obtain fast disintegrant tablet separately.
Embodiment 46 to 51
Repeat the step of embodiment 1, except melting adhesive agent with one of 6000,20 milligrams of PEG6000 of 10 milligrams of PEG, 6000,10 milligrams of PLURONICS F87s of 40 milligrams of PEG, 20 milligrams of PLURONICS F87s and 40 milligrams of PLURONICS F87s as a kind of low temperature, further added in mixed-powder, to obtain fast disintegrant tablet separately.
Embodiment 52
Repeat the step of embodiment 1; except the sweet mellow wine of 300 milligrams are dissolved in the mixed liquor of 10 milligrams of water and 10 milligrams of ethanol; this solution is subjected to wet granulation and processes; the wet particle of gained is dried and as sugar alcohol; rather than with the xylitol of 300 milligrams, the fast disintegrant tablet of being invented to obtain.
Embodiment 53
Repeat the step of embodiment 1; except the sweet mellow wine of the xylitols of 150 milligrams and 150 milligrams is dissolved in the mixed liquor of 5 milligrams of water and 10 milligrams of ethanol; this solution is subjected to wet granulation and processes; and the wet particle of gained is dried and as sugar alcohol; rather than with the xylitol of 300 milligrams, the fast disintegrant tablet of being invented to obtain.
Embodiment 54
Repeat the step of embodiment 1; except the sweet mellow wine of the xylitols of 50 milligrams and 250 milligrams is dissolved in the mixed liquor of 5 milligrams of water, 10 milligrams of ethanol and 5 milligrams of medium chain triglycerides (MTC oil); this solution is subjected to wet granulation and processes; and the wet particle of gained is dried and as sugar alcohol; rather than with the xylitol of 300 milligrams, the fast disintegrant tablet of being invented to obtain.
Embodiment 55
Repeat the step of embodiment 1; except the sweet mellow wine of the xylitols of 50 milligrams and 250 milligrams is dissolved in the mixed liquor of 5 milligrams of water, 10 milligrams of ethanol and 5 milligrams of medium chain triglycerides (MTC oil); this solution is subjected to wet granulation and processes; and the wet particle of gained is dried and as sugar alcohol; rather than with the xylitol of 300 milligrams, and the crosslinked PVP of 30 milligrams is further joined the fast disintegrant tablet of inventing to obtain in mixed-powder as a kind of disintegrant.
Comparative example 1
The oral dispersion tablet (the method Moses's fourth that contains 20 milligrams) of the Gaster trade mark obtaining from the commercialization of Dong-A pharmaceutical Co. Ltd is used as comparison agent.Traditional WOWTAB technology preparation for the oral dispersion tablet of Gaster trade mark.
Test example 1 decomposition run
[disintegration rate]
The disintegration rate of tablet (second) is determined according to the disclosed fundamental test of Korea S drugmaker, by being dropped into 5 ml distilled waters (in a spoon), keeps at room temperature, then measures the time that it decomposes completely.
[disintegration rate in test tube]
The filter paper of 90 mm dias is placed on the culture dish of 100 * 10 millimeters.The distilled water of 7 milliliters sprinkles on culture dish, and culture dish permission inclination, so that filter paper is soaked completely.The definite of the disintegration rate of test tube Chinese medicine tablet (second) is by it being placed on wet filter paper, then measuring the time that it is completely soaked due to capillarity.
[disintegration rate in oral cavity]
The definite of the disintegration rate (second) of tablet in oral cavity is by it being placed on the dry tongue of Yi Wei NAM, then measures the time that it decomposes completely and melt when friction.
The disintegration rate of the tablet obtaining at embodiment 1 to 55 and comparative example 1 and overall taste are determined as mentioned above.The results are shown in Table 1.
Table 1
As seen in Table 1, the invention tablet obtaining in example is with the complete disintegration of time of 2 to 33 seconds in oral cavity, and the delay producing has a gratifying taste for oral.Compare, the Gaster of comparative example 1
tMoral dispersion tablet need to be greater than the disintegration completely in oral cavity of 40 second time.
Thus, the wrapping machine that the preparation method who uses this invention prepares fast disintegrant in the mode of producing in enormous quantities will at length be described.
Blister package machine is typical pharmacy wrapping machine.The term blister package meaning is a kind of packing method, wherein the part of container shapes forms on the flat film of complex or metal manufacture, the part of this container shapes is packed into an object, the part of this container shapes is covered by a lid by adhesive seal, and be drawn as preliminary dimension and cut off, formed like this unit of packing object.In initial ， drugmaker, this blister package method is developed and for pack tablet or capsule at packing material.Blister package method is widely used for sweet food production or manufactures in the operation of cosmetics or household articles at present.The packing method that is different from other, in blister package method because use transparent film, product is easily observed, and because product is used blister-pack, by blister-pack, obtained the shape of product, can be easy to change by changing over the shape of mould, this mould for example has the shape corresponding with product or other various shapes.Further, due to the use of ganoine thin film, product can obtain failure-free protection.In addition, when product is used in hope, because easily product is opened, anyone can use this product.And it has the advantage that Portability is very strong.
A kind of so typical pharmacy wrapping machine has following component part:
(1) film supply unit, for delivery of planar-formed film, this film is for the manufacture of wrapping bottom pockets film.This film supply unit comprises a reeler, and formed film can be pulled down from it and transport, and a taking off tool, and it can take off formed film from reeler with a constant speed.
(2) film forming unit, comprise mould, it has the corresponding shape of the shape required with product, and it is by being placed on formed film on mould and working, and compressing film has formed the pocket of depressing like this on formed film by moving down pressing rod.This film forming unit can comprise regenerator section, it can preheating formed film to improve the plasticity of film.
(3) inclusion input block, has a loading hopper that wherein fills inclusion, and inputs this inclusion in film pocket.
(4) sealing unit, for putting into the bottom pockets film of inclusion by the sealing of top cover film.These packaged unit comprise a reeler, above cover film is looped around with spool-shape, and water-tight equipment.
(5) cutter unit, for being cut into packaging unit by product.As required, this cutter unit can comprise relief equipment to indicate identification symbol or date manufactured, crack equipment to form perforated lines and impact device to carry out blasting operation.
(6) control unit, is arranged on this mechanical front surface.This control unit is controlled mechanical operation according to workman's steering command.For example this control unit can be realized by control desk.
The operation with the pharmacy wrapping machine of above-mentioned structure will be described below.Formed film around on the reeler of film supply unit, is transported and at certain temperature that is suitable for moulding, is carried out preheating by the preheating parts of film forming unit with certain speed.Formed film is immediately pressed bar and suppresses, and the pocket that inclusion is so wherein housed just forms in formed film.Each pocket has the shape of this container.According to like this, with the formed film of pocket, become the bottom pockets film for packing.Then, inclusion (for example pill) is inserted each pocket by inclusion input block.The bottom pockets film that wherein contains inclusion is sent to sealing unit and is combined by suppressing with top cover film, therefore inclusion is sealed up.Subsequently, its cut unit is cut into packaging unit.
In principle, according to pharmacy wrapping machine of the present invention, have above-mentioned structure and operating mode, but its concrete shape and function are not limited.In other words, any wrapping machine can be used with method of the present invention, as long as it has basic blister package function.
Fig. 1 shows the block scheme according to the structure of the wrapping machine for the preparation of oral fast disintegrant of an embodiment of the invention.Fig. 2 is the cross sectional drawing of the medicine material supply unit 130 of wrapping machine.
According to the wrapping machine 100 for the preparation of oral fast disintegrant of the present invention, there is film supply unit 110, film forming unit 120, sealing unit 170, cutter unit 180 and control unit 190 as basic constituent element, similar to typical pharmacy wrapping machine.But, this wrapping machine 100 further comprises medicine material delivery unit 130, it is by powder mixture 20 or the tablet 22 made to form a reservation shape by pressed powder shape compound 20, be input in the pocket 10a of bottom pockets film 10, and there is inclusion input block unlike typical pharmacy wrapping machine.In addition, this wrapping machine 100 further comprises heating unit 160, and its heating is put into the compound of bottom pockets film 10 or tablet to melt and to merge this compound or tablet.
Therefore, according to sequence of positions, arranging is film supply unit 110, film forming unit 120, medicine material delivery unit 130, heating unit 160, sealing unit 170 and cutter unit 180.
Medicine material transports heating 130 input powder mixtures 20, it obtains by hybrid medicine active component and sugar or sugar alcohol powder, or input tablet 22, it is by entering powder mixture 20 compactings in the pocket 10a forming on bottom pockets film 10 and make.
For example, in medicine material delivery unit 130, the powder mixture 20 of right quantity is placed in the hole of powder compression position, and suppresses, and has formed like this tablet 22 of reservation shape.Subsequently, tablet 22 is thrown in the pocket 10a of bottom pockets film 10, and it is placed on the position corresponding with medicine material drain position in advance.
In this embodiment, medicine material delivery unit 130 comprises filling dish 132, and it has two filler opening 132a at least, and it is alternative arrangement between powder compression position and medicine material drain position.Powder mixture 20 is deposited in the upper surface of filling dish 132.Medicine material delivery unit 130 further comprises chassis 134, its be arranged on filling dish 132 below and have an opening 134a, it is opened on filler opening 132a, is arranged on medicine material drain position, and the filler opening 132a that is simultaneously arranged on powder compression position is closed by chassis 134.Medicine material delivery unit 130 further comprises pressing rod 136, it is arranged on, and each filler opening 132a is upper to be entered in corresponding filler opening 132a so that pressing rod 136 moves down, while pressed powder shape compound 20 or discharge tablet 22, then move up, and containing loading hopper 138, it is sent to powder mixture 20 on filling dish 132.
Here, filling dish 132 is circular discs.Have at least two filler opening 132a to be formed on the position separating at space interval with the angle of rule each other through filling dish 132.Filler opening 132a is moved by the rotation of filling dish 132, and is therefore alternately placed on powder compression position and medicine material drain position.
Therefore, after powder mixture 20 is sent to filling dish 132 from loading hopper 138, when filling dish 132 rotation and therefore filler opening 132a moves towards powder compression position and medicine material drain position respectively, the powder mixture 20 of some accumulations is inhaled in corresponding filler opening 132a naturally.When this filler opening 132a arrives powder compression position, filling dish 132 is stopped.Then, corresponding pressing rod 136 moves in this filler opening 132a and enters in filler opening 132a with pressed powder shape compound 20, and the tablet 22 forming like this has gratifying integration power.Subsequently, pressing rod 136 moves up, and filling dish 132 rotates at a predetermined angle, so this filler opening 132a is just placed on medicine material drain position.Then, corresponding pressing rod 136 is moved into downwards in this filler opening 132a, the outside of so downward discharge tablet 22 to filler opening 132a.The tablet 22 of discharging falls in the pocket 10a that enters bottom pockets film 10, and this pocket is placed in medicine material drain position in advance.
Certainly, because all pressing rods 136 move up and down simultaneously, powder compression operation and tablet discharging operation carry out simultaneously.
In summary, the operation of medicine material delivery unit 130 comprises and packs powder mixture 20 into the step of corresponding filler opening, the step of powder mixture 20 and the step of discharge tablet 22 that obsession is loaded.
Here, each filling step and pressing step are performed twice or more times is to be fixed to suitable degree by the content of tablet 22.For this reason, the quantity of the quantity of filler opening 132a and pressing rod 136 can increase with the need.In the case, the rotation step of filling dish 132 is further divided again.
Certainly, fill and during the quantity of pressing step, if a kind of target product, the requirement of the active component of fast disintegrant is relatively little further considering, if or the density of active component relatively high, step number may reduce.
Simultaneously, when being shaped a tablet 22 in powder compression position, when the mobile tablet 22 being shaped is during from powder compression position to medicine material drain position, or Swertia Tablet 22 is while being placed on medicine material drain position, some powder mixtures 20, its filler opening 132a in wherein containing tablet 22, must prevent that it from entering filler opening 132a unexpectedly, to improve the market rate of tablet 22 and the sealing property between top cover film and bottom pockets film 10 around.In order to reach object above, as shown in Figure 3, powder stops instrument 137, and the position before powder compression position extends to the position after medicine material drain position, can be positioned on the upper surface of filling dish 132.Powder stops that instrument 137 can have tabular profile.
In the drawings, reference number 112 represents orienting lug, the motion of its guiding bottom pockets film 10, and reference number 139 represents a leakage preventive sheet, and it prevents that powder mixture 20 on filling dish 132 and filling from coiling 132 unexpectedly separated.
Although machinery of the present invention is demonstrated is configured to powder mixture 20 and is shaped as tablet and is then imported in bottom pockets film 10, it may be constructed to powder mixture 20 and directly be imported in bottom pockets film 10.
Simultaneously, heater block 160 is input to compound or the relatively short time of tablet experience in bottom pockets film 10 in the range of temperatures heating of 200 degree to 1000 degree, from several seconds to tens seconds, like this, melt and integrative mixture or tablet, reduce a kind of decomposition of active constituents of medicine simultaneously.In the example of powder mixture, powder mixture is melted and is merged, and has formed like this pill shapes merging.In the example of tablet, its fusion power can further be strengthened.
Fig. 4 shows the schematic diagram of a representative example structure of heating unit 160;
Here, halide torch, infrared lamp or analogue, it can, at 200 degree or higher temperature heating object, can be used as heat generation device 162.If needed, several lamps can be used as heat generation device 162.
In addition, plate, it can cover on bottom pockets film 10 and block heat is transmitted to bottom pockets film 10 from heat generation device 162, can be used as baffle plate 164.Indentation by baffle plate 164 makes bottom pockets film 10 be exposed to the time of thermal source, can change according to the kind of the component kind in medicine material or bottom pockets film 10 material therefors.
When bottom pockets film 10 advances, the opening and closing of baffle plate 164 are repeated to carry out, to be arranged in compound or the tablet of bottom pockets film 10, with a predetermined open-assembly time, are heated.This operation can repeat and carry out continuously.
Meanwhile, as shown in Figure 5, according to the present invention, for the preparation of the wrapping machine 100 of oral fast disintegrant, can further comprise a press unit 140, it is between medicine material delivery unit 130 and heating unit 160.Press unit 140, for pressing mixt or tablet, in its pocket 10a by the corresponding bottom pockets film 10 of medicine material delivery unit 130 input, has formed the tablet 22 having with pocket 10a respective shapes like this.
As shown in Figure 6, press unit 140 comprises compaction rod 142, and it moves down in the pocket 10a that enters corresponding bottom pockets film 10 and then moves up with pressing mixt or tablet.
Here, for a plurality of step pressing mixts or tablet and form like this compound or the tablet more similar with pocket 10a shape accordingly, several have difform compaction rod and can be placed in front and rear position with pressing mixt or tablet.In the drawings, compaction rod 142 is illustrated as and comprises the first compaction rod, peripheral part of its primary pressing mixt or tablet, and the second compaction rod, the secondly core of pressing mixt or tablet.
In addition, each compaction rod 142, the corresponding compound in being filled into bag-shaped film or tablet, can be with tiny angular turn when downtrodden state.So compound or tablet can be shaped, and do not produce shape to have a kind of uniform shape in pocket 10a destroyed or to lopsidedness.
Meanwhile, as shown in Figure 7, according to the wrapping machine 100 for the preparation of oral fast disintegrant of the present invention, further comprise pump unit 150, it is placed between medicine material supply unit 130 and heating unit 160.Pump unit 150 is filled with therein on the bottom pockets film 10 of compound or tablet and produces swabbing pressure, from bottom pockets film 10, extract like this and remove N/R fine powder, having improved thus the sealing property of 10 of the market rate of product and top cover film and bottom pockets films.
As shown in Figure 8, pump unit 150 comprises air exhaust nozzle 152, the vacuum utility lines of Qi Yu factory or vacuum pump connect to produce vacuum drawn pressure on bottom pockets film 10, and screen 154, it is placed in the position between air exhaust nozzle 152 and bottom pockets film 10, with the compound or the tablet that prevent from being filled in bottom pockets film 10, by vacuum drawn pressure, is upwards taken away.
Here, air exhaust nozzle 152 can move downward or upward so that it is near bottom pockets film 10 or remove therefrom.
According to the present invention, have the structure of carrying above in order to the overall operation of preparing a kind of wrapping machine 100 for oral fast disintegrant by as described below.
First, from film supply unit 110, with a constant speed, carry a formed film.This formed film is preheated and by film shaped parts 120 compactings, the pocket 10a like this with container shapes forms on this formed film, has therefore formed bottom pockets film 10.
Subsequently, pulverulent mixture or tablet are placed in the corresponding pocket 10a of formed bottom pockets film 10 by medicine material supply unit 130.The compound or the tablet that are filled in pocket film are pressed by press unit 140 in the corresponding pocket 10a of bottom pockets film 10, have formed like this tablet 22 having with pocket 10a shape respective shapes.
Subsequently, the N/R fine powder on bottom pockets film 10, the vacuum pressure by pump unit 150 is removed.
Compound in bottom pockets film 10 or tablet are being heated by heating unit 160 thereafter, so each compound or tablet melted and merge to guarantee necessarily firmly binding force, are configured as thus a kind of for oral fast disintegrant.
Then, the bottom pockets film 10 that comprises quick orally disintegrating dosage form, is pressed on the cover film of top and is sealed like this by sealing unit 170, has therefore completed packaging operation.Subsequently, the cut unit 180 of product is cut into predetermined packaging unit.
Finally, packaged being somebody's turn to do for oral fast disintegrant product, at room temperature cooling lentamente with the state of packing.
Thus, for oral fast disintegrant, can facilitate and by independent manufacturing line, use production in enormous quantities method to prepare economically.
In the present invention, although being illustrated as, furnace run use heating unit 160 to be implemented as an intermediate steps of packing processing, furnace run also can be implemented after top cover film is attached to finishing dealing with on bottom pockets film, after packing is finished dealing with, carries out.For this reason, after the packing of fast disintegrant product is finished dealing with, product can be placed in heating cavity, so product heats individually.
When above reference, the present invention of specific embodiment is described, be interpreted as those skilled in the art for the various changes of this invention enforcement and change being also included into by within defined this scope of invention of accessory claim.
Claims (16)
1. for the preparation of a wrapping machine for oral fast disintegrant, comprise:
Film supply unit, in order to carry the film forming;
Film forming unit, in order to the film that is shaped and forms, thereby forms the bottom pockets film that is provided with container shapes pocket;
Medicine material supply unit, to load or to be input in the bag of described bottom pockets film by pulverulent mixture or by suppressing the described pulverulent mixture tablet that extremely predetermined shape forms;
Heating unit, the compound of being loaded to heat or tablet, thereby compound or tablet that thawing and combination are loaded; And
Sealing unit, in order to be attached to top cover film on described bottom pockets film.
2. according to wrapping machine claimed in claim 1, further comprise:
Cutter unit, packing are cut into predetermined unit, these packing are by being attached to described top cover film on described bottom pockets film and forming; With
Control unit, for operating control.
3. according to wrapping machine claimed in claim 1, wherein said pulverulent mixture comprises active constituents of medicine and sugar or sugar alcohol powder.
4. according to wrapping machine claimed in claim 2, wherein said pulverulent mixture further comprises the pharmaceutically acceptable additive that is selected from lower group: low temperature melts adhesive agent, disintegrant, lubricant, excipient, and composition thereof.
5. according to wrapping machine claimed in claim 1, wherein said medicine material supply unit comprises:
Have at least two filling dishes of loading hole, it is placed in respectively and alternatively powder compression position and medicine material drain position, and this filling dish allows described powder mixture to be deposited on its upper surface;
Be located at described filling dish chassis below, for opening the described filling hole that is arranged at described medicine material drain position, and close the described filling hole that is arranged at described powder compression position;
Be positioned at each and load the pressing rod above hole, described pressing rod is moved down in corresponding filling hole to compress the powder mixture in the filling hole that is filled into described powder compression position simultaneously, and discharges the tablet in the filling hole that is arranged in described medicine material drain position; And
Loading hopper, for transporting described powder mixture to described filling dish.
6. according to wrapping machine claimed in claim 5, wherein, rotate described filling dish, and in the rotary course of described filling dish, piled up powder mixture is transported in corresponding filling hole.
7. according to wrapping machine claimed in claim 5, wherein said powder compression position comprises at least two powder compression positions, so that transporting and be compressed in a plurality of steps of described powder mixture implemented.
8. according to wrapping machine claimed in claim 5, wherein said medicine material delivery unit further comprises:
The powder being arranged on described filling dish stops instrument, and for stoping extra powder mixture to enter described filling hole, powder barrier plate extends to the position after described medicine material drain position from the position before described powder compression position.
9. according to wrapping machine claimed in claim 1, wherein said heating unit comprises:
Heat generation device, for heating compound or the tablet that is filled in described bottom pockets film; With
Baffle plate, inserts the space between described heat generation device and described bottom pockets film for telescopically, thereby controls the time period that described compound or tablet are heated.
10. according to wrapping machine claimed in claim 9, wherein said heat generation device comprises halide torch or infrared lamp.
11. according to wrapping machine claimed in claim 1, further comprises:
Press unit, for pressing mixt or tablet, it is imported in the pocket of described bottom pockets film by medicine material delivery unit, thereby described compound or tablet are configured as to the corresponding shape of shape with described pocket.
12. according to the wrapping machine described in claim 11, and wherein said press unit comprises:
Compaction rod, moves up in order to be moved down in the pocket of described bottom pockets film and after the described compound of compacting or tablet.
13. according to the wrapping machine described in claim 12, and the compaction rod of wherein said press unit comprises at least two compaction rods that arrange continuously, in order to the described compound of continuous compacting or tablet at least twice.
14. according to the wrapping machine described in claim 13, each compaction rod of wherein said press unit is filled in compound or the tablet rotation afterwards in described pocket with compacting in the pocket that is moved down into described bottom pockets film, and described compound or tablet are evenly shaped in described pocket.
15. according to the wrapping machine described in claim 1 or 11, further comprises:
Pump unit, for produce swabbing pressure on described bottom pockets film, thereby extracts and removes N/R fine powder from described bottom pockets film.
16. according to the wrapping machine described in claim 15, and wherein said pump unit comprises:
Air exhaust nozzle, for producing vacuum draw pressure on described bottom pockets film; With
Barrier, is placed in the position between described air exhaust nozzle and described bottom pockets film, with compound or the tablet that prevents from being filled in described pocket film, by vacuum draw pressure, is upwards aspirated.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020070063757A KR100912351B1 (en) | 2007-02-14 | 2007-06-27 | Method for preparing rapidly disintegrating formulation for oral administration and medicine packing machine for the same |
| KR10-2007-0063757 | 2007-06-27 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008800224698A Division CN101686942B (en) | 2007-06-27 | 2008-06-25 | Method for preparing rapidly disintegrating formulation for oral administration and apparatus for preparing and packing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102424151A CN102424151A (en) | 2012-04-25 |
| CN102424151B true CN102424151B (en) | 2014-03-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110233231.3A Expired - Fee Related CN102424151B (en) | 2007-06-27 | 2008-06-25 | Apparatus for preparing rapidly disintegrating formulation for oral administration |
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| Country | Link |
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| CN (1) | CN102424151B (en) |
| HK (1) | HK1165769A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI661940B (en) * | 2016-11-10 | 2019-06-11 | 林伯衡 | Apparatus and method for manufacturing herb tablets |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5603880A (en) * | 1994-07-07 | 1997-02-18 | Sankyo Seisakusho Co. | Method and apparatus for manufacturing tablets |
| CN1473036A (en) * | 2001-05-10 | 2004-02-04 | ֮����ҩ��ʽ���� | Tablets quickly disintegrating in oral cavity and process for producing same |
| CN1882303A (en) * | 2003-09-24 | 2006-12-20 | 生物进展技术有限公司 | Improvements in powder compaction and enrobing |
| CN1956695A (en) * | 2004-05-18 | 2007-05-02 | I.M.A.工业机械自动装置股份公司 | A capsule filling machine and method for producing hard gelating capsules |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4731767B2 (en) * | 2001-09-19 | 2011-07-27 | 株式会社ミューチュアル | Blister packaging machine film thermoforming method and apparatus |
-
2008
- 2008-06-25 CN CN201110233231.3A patent/CN102424151B/en not_active Expired - Fee Related
-
2012
- 2012-06-29 HK HK12106398.1A patent/HK1165769A1/en not_active IP Right Cessation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5603880A (en) * | 1994-07-07 | 1997-02-18 | Sankyo Seisakusho Co. | Method and apparatus for manufacturing tablets |
| CN1473036A (en) * | 2001-05-10 | 2004-02-04 | ֮����ҩ��ʽ���� | Tablets quickly disintegrating in oral cavity and process for producing same |
| CN1882303A (en) * | 2003-09-24 | 2006-12-20 | 生物进展技术有限公司 | Improvements in powder compaction and enrobing |
| CN1956695A (en) * | 2004-05-18 | 2007-05-02 | I.M.A.工业机械自动装置股份公司 | A capsule filling machine and method for producing hard gelating capsules |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102424151A (en) | 2012-04-25 |
| HK1165769A1 (en) | 2012-10-12 |
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