CN101370483A - Dosage form for adhesion connection - Google Patents
Dosage form for adhesion connection Download PDFInfo
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- CN101370483A CN101370483A CNA2005800525600A CN200580052560A CN101370483A CN 101370483 A CN101370483 A CN 101370483A CN A2005800525600 A CNA2005800525600 A CN A2005800525600A CN 200580052560 A CN200580052560 A CN 200580052560A CN 101370483 A CN101370483 A CN 101370483A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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Abstract
A pharmaceutical dosage form that is an adhesively bonded aggregate of preformed subunits that may be conveniently breakable into smaller parts.
Description
Technical field
The present invention relates to solid pharmaceutical dosage formulation, it comprises the aggregation of the preformed subunit that adhesively links together.
Background technology
Be provided for carrying the dosage form of material of premeasuring such as tablet or capsule by as everyone knows, described dosage form makes consumer can use multiple material and does not need to use costliness and heavy measuring device.Reason of the present invention is the flexible administration that takes into account one or more medicines.
People (this paper such as the uncensored Ito of Japan, " Ito ") the open H6-9375 of patent application disclose by less " unit tablet " (this paper " subunit ", or " tablet subunit ", or " capsule subunit ") tablet formed, " binding agent (cement) " that described unit tablet is used as binding agent (adhesive) connects.The coupling part clearly is defined as binding agent under those situations, advocate that described binding agent for what can disconnect, stays complete unit tablet.Except mechanically or by dissolving ground, the example that disconnects in described binding agent connecting portion office, this application discloses the product of the tablet of less tablet configuration, its each contain complete unit tablet.It is not the tablet subunit of " unit tablet " that this application is failed open.In addition, this application is specific on the production model of its disclosed described tablet.Described production model reaches subsequently and forms " coupling part " composition with binding agent by making connected unit tablet (" coupling ") arranged side by side.Described application is unexposed produces described tablet by the mode that inertia subunit not arranged side by side with another subunit simultaneously or that close on is used binding agent.
In addition, be " unit tablet " because Ito states the subunit of described application, should not be encompassed in and make the indentation that is generally used for promoting the tablet disconnection in the unit tablet.In addition, the labelling on the tablet, as the labelling of the marking, it also can promote tablet to disconnect as by delineating the aliquot of tablet subunit, can not comprised by the application of Ito similarly.The present invention uses term " separation marking (separation mark) " or " separation marking (separation marking) " expression indentation, marking labelling, or on the tablet subunit may command or promote the similar additament that tablet disconnects.
The present invention is extremely obviously different with the disclosed implication that openly reaches him of Ito, because containing the dosage form of his invention, described application all absorbed, otherwise only locate to be disconnected or separately at " binding agent ", described dosage form contains the tablet subunit that is taken as " structural unit ", and described " structural unit " is as the inseparable atom that forms molecule.On the contrary, the open dosage form of the present invention, it is suitable for partly disconnecting at the tablet subunit of described dosage form.Therefore, the method that disconnects dosage form of the present invention is included in that tablet subunit place disconnects and does not locate to disconnect at binding agent (adhesive) (binding agent (cement)).
The present invention uses the generic term 'inertia' to describe the tablet subunit that does not contain any active pharmaceutical ingredient (i.e. " medicine ").'inertia' is intended to comprise the tablet subunit that does not contain any sustained release function or have the sustained release function.Use the tablet subunit of term " non-activity " to represent not contain any active pharmaceutical ingredient and also do not contain any rapid release function.Therefore, the tablet subunit of any non-activity also is considered to inert, but the inert tablet subunit can or can not be inactive.
Summary of the invention
The present invention relates to novel dosage form and their manufacture method, disconnect the addition method of described dosage form and using of described dosage form breaking part.
The invention provides contain a plurality of bonding-solid pharmaceutical dosage formulation of the subunit that connects.Described dosage form comprises following at least one or a plurality of subunit:
A. (i) first inert tablet subunit and the (ii) second active subunit;
B. (i) has the first tablet subunit of pharmacology non-activity layer, and in this tablet subunit, described layer quality is at least the 20mg and (ii) second subunit;
C. be provided with the tablet subunit of separation marking; Or
D. (i) first tablet subunit and the (ii) second capsule subunit.
Dosage form by place a plurality of pre-form between the subunit and connect (joining) (or, " connect (connecting) ", or " connect (bonding) ") adhesion substance that is fit to of a plurality of pre-formation subunits forms, described subunit preferred tablet but may comprise one or more capsule subunits.It is different that the present invention and Ito disclose, because the present invention relates at least a following novel aspect:
A. in preferred embodiments, the dosage form that comprises the tablet subunit (" inert tablet subunit ") that at least one tablet subunit that contains active medicine (" active subunit ") and at least one only made by pharmacy non-activity material is open by this paper, and Ito only discloses the exemplary placebo tablet of only being made by the non-activity subunit;
B. in a further preferred embodiment, dosage form comprises two or more bonding connections active subunit together, and wherein at least one active subunit has separation marking, preferred indentation;
C. in a further preferred embodiment, dosage form has two or more bonding connections in the active subunit of one or more inert tablet and in described embodiment, and separation marking is to choose wantonly as indentation;
D. in another embodiment, the capsule subunit can with the bonding connection of tablet subunit; Or
E. in a further preferred embodiment, the present invention relates to contain the dosage form of a plurality of active subunits, each connects an inertia subunit that is easy to disconnect and does not damage any active subunit described active subunit.
The non-activity tablet subunit of dosage form of the present invention is preferably suitable for disconnecting, as possesses the tablet subunit of separation marking, and described separation marking can be indentation; This type of subunit can randomly be the subunit of activity or non-activity.Active tablet subunit also can be suitable for disconnecting easily and can possessing separation marking such as indentation.
The active subunit of this paper contains a medicine or a plurality of medicine of pharmacologically effective dose.This paper term " medicine ", " active medicine ", " active pharmaceutical ingredient " or " active component ", " active pharmaceutical compounds " and similar terms not only comprise medicine as in the U.S. by the medicine of food medicine surveillance authority supervision, also comprise vitamin and mineral.
In many cases, the inertia subunit will connect two independent active subunits.Term used herein " inert tablet subunit " refers to the construction unit made on preforming device, wherein said construction unit comprises pharmaceutically acceptable material, as excipient, diluent, filler etc., described pharmaceutically acceptable material does not have detectable pharmacological action with institute's use amount in the dosage form.
When using term " non-activity subunit ", it does not have the subunit that can detect pharmacological action and not have the sustained release function in order to describe.
The invention provides a kind of method, its pre-determining section that dosage form can accurately be provided is to use and to provide complete dosage form.Preferably but not always, do not disconnect subunit of the present invention and will not comprise between destruction, damage, dissolving subunit bonding connection etc.A kind of usage that it is considered herein that dosage form can be included in the disconnection of two or more subunits place, and its unitary part place that is also included within the bonding connection that connects subunit disconnects.
The present invention also comprises the method for the part of the active subunit of using solid pharmaceutical dosage formulation, and this method partly reaches subsequently to the Orally administered part that contains active subunit of the patient that its needs are arranged to obtain containing active subunit by disconnect described pharmaceutical dosage form at active subunit place.
Further embodiment relates to the method for an active subunit of form of administration, described dosage form contains at least two active subunits with the bonding connection of inert tablet subunit, described method at first disconnects described inert tablet subunit to form two parts, each part comprises the inertia subunit of an active subunit and a part of described disconnection, and subsequently patient or other suitable host is used a described part.Be intended to dosage form with through disconnecting the part enteral administration that forms, as oral.Also contain other application process, as passing through naso gastric tube or gastrostomy tube or process rectum.
A part of pulverizing by the whole dosage form of the inventive method through disconnecting formation is contained in the present invention, so that can realize easily through using of feed pipe or analog.
The present invention further comprises the method for making solid pharmaceutical dosage formulation, by:
(a) at first, use binding agent to the first active subunit or the first inertia subunit; And
(b) secondly, make described first to contain the activity of binding agent or inertia subunit and contact second activity or inert tablet subunit (it randomly also can contain the binding agent of application) and randomly exert pressure to subunit.
Final dosage form should be understood that character, content, active component or non-activity composition, or size or shape do not apply restriction, except should safe in utilization and most preferably can be expected that user receives (as absorbing) in the body by it to subunit or final dosage form.
The present invention uses has the material of enough adhesive powers so that subunit is bonded to each other to form adherent dosage form.For commercial use, preferably described dosage form will be kept perfectly until its arrival patient, nurse, pharmacists etc. through production and transportation.These novel dosage forms have many embodiments and can comprise many different arrangements, many difformities, active component type, non-activity component type, subunit number etc., without any restriction.This paper provide represent embodiment of the present invention example with example, but be not limited in the quantity of the effective probability in the scope of the invention.
Therefore, it is a principal object of the present invention to provide the newtype drug dosage form that contains one or more activity or non-activity composition, described activity or non-activity composition are in the active subunit more than the independent production of a bonding connection on inertia connector subunit, wherein said dosage form can disconnect by a position in active subunit or a plurality of position and be separated into two or more parts, determines to measure so that a kind of medicine or the pre-of multiple medicine that are included in the described dosage form to be provided.
The newtype drug dosage form that contains one or more activity or non-activity composition is provided, described activity or non-activity composition are in the active subunit more than the independent production of a bonding connection on inertia connector subunit, wherein said dosage form can disconnect by a position in the inertia subunit or a plurality of position and be separated into two or more parts, determines that so that a kind of medicine or the pre-of multiple medicine that are included in the described dosage form to be provided amount also is a target of the present invention.
The newtype drug dosage form that contains one or more activity or non-activity composition is provided, described activity or non-activity composition are in the active subunit more than the independent production of a bonding connection on inertia connector subunit, wherein said dosage form can determine that so that a kind of medicine or the pre-of multiple medicine that are included in the described dosage form to be provided amount also is a target of the present invention by being separated into two or more parts at one or more active subunits and a plurality of positions disconnection in inertia connector subunit.
These targets of the present invention and other target will become obvious from this description.
" subunit " is the pre-formation structure that this paper classifies, or as active subunit, capsule subunit or as inert tablet subunit or non-activity tablet subunit.Material such as adhesion substance or can be used for the thin film such as the HYDROXY PROPYL METHYLCELLULOSE of coating subunit, himself is not considered subunit.
" pre-formation " refers to the independent production of subunit.The tablet subunit of dosage form of the present invention is produced as tablet, and when it becomes dosage form part of the present invention, becomes subunit.Similarly description also is applied to capsule subunit of the present invention.
Tablet subunit of the present invention can be hierarchy, as everyone knows.The pharmacology non-activity layer that invention can comprise the tablet that contains a plurality of layers is with as cut-off point and therefore can play a part similar to the inert tablet subunit in the present invention at described pharmacology non-activity layer.Preferably, described non-activity layer quality is at least 20mg and 50-900mg more preferably; Or 150mg-750mg or 400-600mg; At least 10 cubic millimeters volume and more preferably 25 cubic millimeters; And/or be at least 1mm, and 2mm more preferably along the length of the major axis of dosage form.Therefore, described non-activity layer can be through playing an important role as areas of disconnection in the dosage form layering.
" tablet " and " capsule " is defined in their common mode.Active subunit can comprise one or more medicines.
This paper " pharmaceutical dosage form " refers to contain the solid dosage forms of two or more bonding connections subunit together.Preferred solid dosage forms is a peroral dosage form.
Description of drawings
Institute's drawings attached has been described dosage form of the present invention, wherein closes on the subunit bonding connection.All views are external view.
Fig. 1 is a top view of describing the dosage form of the present invention that three subunits are arranged.
Fig. 2 has three subunits, and one of them is by the top schematic view of the dosage form of a horn silver AgX coin shape of indentation.
Fig. 3 describes the top schematic view that is connected in four active subunits of an inert tablet subunit by adhesion substance separately.
Fig. 4 describes five tablet subunits, wherein two other three subunits of bonding connection separately.
Fig. 5 is a top schematic view of describing the dosage form of the present invention of capsule form.The inert tablet subunit has two grooves that contain the active subunit of pre-formation separately.
Fig. 6 is a diagrammatic side view of describing the dosage form of being made up of three band active tablet subunits indentation, bonding connection.
Fig. 7 is a diagrammatic side view of describing the dosage form of being made up of three active tablet subunits, and described three active tablet subunits are two inert tablet subunits of bonding connection separately.
Fig. 8 is the top schematic view of three-subunit dosage form.
Fig. 9 is the top schematic view of four-active subunit dosage form, and four active subunit bonding connections together in described dosage form.
Figure 10 describes the side view of the dosage form that contains four tablet subunits.
Figure 11 describes the dosage form that contains five subunits.
Figure 12 describes the dosage form that contains three three subunits that adhesively link together.
Figure 13 describes and contains three tablet subunits, and it does not all have the dosage form of indentation.
Figure 14 describes and contains three subunits, the dosage form of one of them indentation.
Figure 15 is two subunits, and one of them is the analysis diagram of the dosage form of tri-layer tablets subunit.
Figure 16 contains two active subunits, and one of them is that tablet subunit and one of them are the capsule subunits, and the part of the dosage form of an inert tablet subunit is resolved perspective view.
Figure 17 contains four active subunits and combines the perspective view that the part of dosage form of the inert tablet subunit of described active subunit is resolved with one.
Figure 18 is the perspective view that contains two active subunits and resolve with the part of the dosage form of an inert tablet subunit with the score marks that places in the inert tablet subunit.
The specific embodiment
It is considered herein that active subunit contain a kind of medicine or multiple medicine, capsule subunit be active subunit (except being used for the placebo preparation and the similar formulations of clinical trial), and the inert tablet subunit do not contain medicine.
Dosage form of the present invention can be manufactured through connecting independent tablet or capsule, described tablet and capsule with any desired shape by molding, by these class methods as using tablet machine and compression mold (tablet), or encapsulate capsule equipment (encapsulating equipment) (capsule).Described production method is unrestricted.Method of attachment comprises the material with bond property.Between subunit, can additionally there be material with non-adhesive characteristics.
Dosage form can comprise active subunit and the inert tablet subunit with a plurality of different cross section shapes, non-limiting circular tablet, semicircle, 1/4 circle, ellipse, trapezoidal, triangle, rectangle etc. of comprising, and it adhesively is connected to each other.In the preferred embodiment of the invention, active subunit and/or capsule subunit can not damaged the function of described subunit in mode easily from separated from one another by terminal use, nurse, pharmacists etc.Preferably, at least one active subunit (containing or do not contain part inert tablet subunit) this type of harmless separation from dosage form can manually be finished; Yet, can exist the manual separation inconvenience maybe can damage the situation of one or more subunits.In the case, within the scope of the present invention, can exist, use as instruments such as commercially availabie tablet cutting machine, kitchen cutter at least one subunit isolating mechanical means easily from complete dosage form.Because the dosage form of the subunit that contains multiple shape is contained in the present invention, its some dosage form contains more than two subunits, therefore may be inconvenient to use the standard tablet cutting machine, and therefore expectation manufacturing is applicable to that especially special form with the isolating tablet cutting machine of the harmless subunit of optimization also within the scope of the present invention.
The application of the invention method can be made the pharmaceutical dosage form that contains two or more independent subunits.
Usually, use the effective dose binding agent so that any two surfaces are linked together.As for the amount of required binding agent, do not plan to limit.The amount of required binding agent depends on multiple factor, as the size and the density of dosage form.Usually, the minimum of preferred adhesive.Usually, the amount of binding agent can comprise from 0.1 to the 5 English silk that covers the binding agent on approximate 0.5 to 100 square millimeter of area, more or less, depends on the specific tablets size and is connected in together surface area and quantity.Under veterinary's dosage form situation, this area can significantly increase.
Fig. 1 is a diagrammatic side view of the present invention, and it describes two active subunits, 52 and 54, respectively, connected by inert tablet subunit 56.Binding agent is connected in active subunit 52 inert tablet subunit 56 1 sides and also active subunit 54 is incorporated into inert tablet subunit 56 opposite sides. Active subunit 52 and 54 can be easily from separated from one another, for example, by in the cutting of inert tablet subunit 56 places, or by firmly grasping active subunit 52 and 54 and exert pressure at inert tablet subunit 56 centers, comprises rotational pressure or pressure at right angle.Active subunit 52 is identical in fact with 54.
Accompanying drawing is unnecessary to be drawn to scale, and is not intended to limit the size or the shape of dosage form or any subunit.Among inert tablet subunit such as the figure subunit 56 usually quality greater than 20mg or more preferably from 50mg to 900mg, or also will be more preferably from 150mg to 600mg or also will be more preferably from (form) 400mg to 500mg.With select length and thickness with guarantee dosage form can by enteral use simultaneously enough firm with avoid packing, excessive breakage during shipping and the carrying.
As shown in Figure 2, circular (coin shapes is as a horn silver AgX coin shape) dosage form provides with top view, and it contains the active tablet subunit 62 and 6 of the inert tablet subunit 66 that is connected in the indentation with indentation 68 separately.Inert tablet subunit 66 can not damage active subunit 62 or active subunit 64 through manual or mechanical disconnection easily.Randomly, this shape dosage form also can contain an indentation or two active tablets of indentation all.
Fig. 3 has described four active subunits 72,74,76 and 78 that are connected to inert tablet subunit composition 79 through adhesion substance, if described active subunit disconnect can provide one or more can absorbed subunit.
Fig. 4 shows three active subunits, 80,82 and 84, and its neither being connected to each other, but all be connected in inert tablet subunit 85 and 86 at the two ends of active subunit.Disconnecting dosage form at inertia subunit place can be implemented, and does not damage any active subunit.Do not point out similar Design, wherein active subunit only at one end is connected to the inert tablet subunit.In practice, the gap between active subunit 87 and 89 is littler shown in comparable.Fig. 4 does not get rid of the probability that in fact the active subunit of arrangement like this contacts.
Fig. 5 is the dosage form that comprises three subunits.Active subunit 92 and 94 is connected in groove (recessed groove) 92A and the 94A that forms bondedly in subunit 90.Subunit 90 can be also inert tablet subunit of the active subunit that contains active component or subunit 90.Can be made into to contain the multiple shape of difform groove or recessed groove with the similar dosage form of Fig. 5.Complete dosage form can not absorb.This dosage form can be disconnected at indentation 96 places so that the active subunit in the dosage form is separated into two parts.
As shown in Figure 6, dosage form of the present invention can comprise the generally flat active subunit 8,10 and 12 that stacked multilamellar is arranged, its respectively, contain score marks 5,7 and 9 and its adhesively be joined together to form layer structure with a little binder 6.
Fig. 7 shows dosage form, three active subunits wherein, 14,16 and 18 and bonding connection be fixed together in the inert tablet subunit 20 and 22 of each active subunit one side.Though Fig. 7 is presented at lateral two the inert tablet subunits of tablet, may only use one, two or a plurality of inert tablet subunit, it can be positioned to form stable and useful dosage form.
Fig. 8 describes the top view of the dosage form contain the inert tablet subunit 34 that connects 36 and 38 the edge that contains active component.The edge of line 40 and the active subunit bonding connection of 42 representatives.If expectation, it does not conveniently influence arbitrary active subunit in the disconnection of inert tablet subunit place.
Fig. 9 shows the top view of four-active subunit dosage form, and described dosage form is made by segment 24,26,28 and 30 is adhesively linked together, and each is 90 ° of arcs of net shape contribution of dosage form for described segment.When some different activities medicines was used in expection simultaneously, this dosage form was particularly useful.Indentation 27 is five equilibrium subunit 30 and indentation 29 five equilibrium subunit 26 approx approx.This dosage form can be separated easily therefore at two indentation places, and two indentations form a successive linear grooves across dosage form.With the binding agent of the same type of adhesive therefor among Fig. 66 subunit is linked together.
Figure 10 shows the dosage form of three-active subunit, and in described dosage form, exterior active subunit 100 is connected in the active subunit 102 in middle part with adhesive layer 10l.Outside subunit 104 is connected in inert tablet subunit 103 with binding agent, and the latter adhesively is connected in the active subunit 102 in middle part.
Figure 11 shows the dosage form of three-active subunit, and in described dosage form, exterior active subunit 105 and 109 adhesively is connected in inert tablet subunit 106 and 108 separately, and described inert tablet subunit is connected in the active subunit 107 in middle part respectively bondedly.
Figure 12 shows the dosage form of three-active subunit, and in described dosage form, active subunit 110 is connected in the active subunit 112 in middle part with binding agent 111.Active subunit 114 is connected in the active subunit 112 in middle part with binding agent 113.
Figure 13 shows the inert tablet subunit 116 that adhesively is connected in active subunit 115 and 115A.Described active subunit comprises same medicine.This dosage form can be disconnected easily at 116 places of the subunit between subunit 115 and the 115A.
Figure 14 has described the inert tablet subunit 118 that contains an indentation between different activities subunit 120 and 120A, and when wishing, it can promote tablet to disconnect.
Figure 15 with outside view description the dosage form of forming by two tablet subunits that on the contact surface 308 that contains adhesion substance, adhesively link together.The tablet subunit of being made up of layer 300,302 and 304 is produced on three laminate machines respectively.At layer 300 and 302 intermediary vertical lines, and at layer 302 and 304 intermediary vertical lines, represent the contact surface between the layer, described line is all different colours.Layer 300 comprises the amlodipine benzenesulphonate (amlodipine) of therapeutic dose and the chlortalidone that layer 304 comprises therapeutic dose.Layer 302 is made with the non-activity granule, and owing to form in the technology at tablet and to mix between layer, contains the amlodipine and the chlortalidone of pharmacology ineffective dose.Described tri-layer tablets is a subunit of the dosage form described among Figure 15, and it is produced at first enters mould by the granule that makes the excipient that contains amlodipine and be fit to, compacting subsequently; Make the granule that does not contain active component enter mould subsequently, compacting makes the granule that contains amlodipine enter mould subsequently subsequently, pre-stamped subsequently and abundant subsequently the compacting to form the tablet of cohesion.Upper cut-out is that inclined-plane and lower cut-out are the plane.
The advantage of the dosage form of describing among Figure 15 is that dosage form that aforesaid tri-layer tablets (layer 300,302 and 304) can be used for producing more complex, three kinds of active medicines, Figure 15 remains on layer 302 place simultaneously and disconnects the ability of dosage form and produce two useful dosage forms.Dosage form can only comprise the therapeutic dose amlodipine and another can only comprise the chlortalidone and the benazepril of therapeutic dose.
Many other variants of the design of the dosage form of describing in Figure 15 can be used in the present invention.
Figure 16 resolves perspective view by the part of the dosage form that bonding connection is formed in the component 203 of subunit 208.In this example, subunit 200 is capsule subunits.Component 203 comprises subunit 200 and inert tablet subunit 204.
The length of subunit 204 makes it be easy to relatively disconnect with respect to other subunit.
Figure 17 has described the external view of the dosage form that contains four active tablet subunits that all adhesively are connected in non-activity connector tablet subunit 218.
Subunit 210,212,214 and 216 all is active.In present example, each contains the different pharmaceutical of therapeutic dose in the described active subunit.In an alternative embodiment, two or more active subunits can comprise same medicine.
Notice that tablet subunit 214a is shown with its appropriate location in the dosage form of Figure 17 and also analyse and observe the analysis diagram demonstration as 214b with part.
Figure 18 has described the part of the dosage form that contains component 234 and has resolved external view, and described 234 contain non-activity tablet subunit 227, contact surface 230, tablet subunit 232 and the Lac layer 224 of two indentations; And tablet subunit 220.Top indentation 226 and bottom indentation 228 are manually made with file.
The tablet subunit that adhesively links together can use that the technology in order to the production conventional tablet is made in this type of technology such as the pharmaceutical industries.These technology comprise, are not limited to: wet granulation; The dry granulation technology is as slugging and grinding; Or direct pressed powder mixture.
Medicinal usage
Usually, many useful solid dosage formss can be produced effectively with the inventive method.The present invention has some advantages of putting into practice.These advantages comprise, are not limited to:
A. when wishing to merge to different product in the dosage form, no longer need common preparation.The inventive method not only will be saved time and money in this development, and this class saving will make it be easier to promote the therapeutic alliance test.The incompatible discussion that makes people's worry will no longer limit between the different preparations.Some other physics and chemistry discussion also will no longer be limited.
B. the same pharmaceutical product of two or more dosage can be produced independently, is connected as tablet subunit or capsule subunit subsequently.If can obtain subsequently than the accessible more accurate administration of the traditional indentation tablet of current usefulness accurately from separated from one another.About connecting two capsules, current do not possess the market-oriented product that capsule formulation is separated into the ability of two capsule subunits in the U.S..
C. the present invention can be joined together tablet and capsule in a dosage form, and it has promoted drug world with novel and potential important way.
D. the doctor of therapeutic alliance and patient approval, sure with science, government is sure, the approval of supervision department, and society is certainly, allows the motility of joint product dosage generally to be strengthened by following the inventive method.
E. the present invention is suitable for preparing the combination medicine product, promptly contains the dosage form of two or more active component.When dosage form of the present invention contained more than a kind of active medicine, dosage form of the present invention can the method for providing convenience be improved the patient compliance of dosage regimen is minimized formulation problems simultaneously at one time.These benefits are in addition for stopping the advantage with the treatment of one or more medicines, by remove the one or more subunits that contain specific drugs from dosage form.Further benefit is the simplification of writing out a prescription and making up a prescription of multiple drug alone product.
F. can disconnect certain preferred embodiments of the present invention to member patient hypersensitive in the joint product and absorb a medicine in the associating tablet, it still can not be realized safely at present.
The invention provides the method for the dosage form of making the different pharmaceutical associating, different pharmaceutical can separate from associating in described dosage form, appears in the associating with another medicine without any the other medicines of trace.For example, when multilayer tablet is formed on the multilamellar tablet machine, be difficult to or may stop particulate all traces of one deck to appear in another particulate neutralizing layer hardly, disperse on the zone in the mould or form aerosol shape dispersion because air-flow and vibration cause granule to be fed on the multilamellar tablet machine.The present invention can be connected the separation component that merges dosage form respectively bondedly by tabletting and in this type of mode, described mode is according to the present invention, and drug alone does not have transverse migration between the isolating active unit of dosage form.Like this, when active subunit leaves dosage form of the present invention and obtained, do not exist the layer of wearing of drug alone to pollute.When the patient was irritated to specific drugs, this was even more important.
As above mention, it is considered herein that solid dosage forms generally can benefit from the present invention instruction.Next be also can with some specific example of the product of some useful medication combined gangs, its example is in bracket:
The associating of antianginal agent.These unite any associating that comprises following drug categories:
A. calcium ion channel blocker (Amlodipine, diltiazem, lercanidipine)
B. beta-Blocking agent (atenolol, metoprolol, Propranolol)
C. organic nitrate goods (isosorbide mononitrate or dinitrate);
The associating of antianginal agent (on seeing) and anti-platelet agents is as aspirin or clopidogrel;
The associating of any two kinds of Hypoylycemic agents;
The associating of potassium salt (preferred KCl) and any thiazide-type diuretic or medullary loop diuretic;
The associating of any in lipid-lowering agent and the multiple representative drugs classification, described classification has: Hypoylycemic agents, anti-platelet agents, antianginal agent, organic nitrate, hypotensive agent;
Lipid-lowering agent can be:
Member's (nicotinic acid, Elastase, acipimox) of inhibin (simvastatin, the atorvastatin that contains or do not contain Torcetrarib, rosuvastatin, lovastatin, rosuvastatin, fluvastatin), fibrates derivant (fenofibrate, gemfibrozil, bezafibrate, ciprofibrate, chlorine Bei Te) or other classification.
Hypoylycemic agents:
Thiazolinedione: pioglitazone, rosiglitazone
Sulphanylureas: glibenclamide, glipizide, glimepiride, chlorpropamide
Biguanides: metformin
Meglitinide: Nateglinide, repaglinide
Glucosidase inhibitor: acarbose, miglitol;
Below two or more member in three kinds:
A. diuretic (HCTZ, furosemide)
B. digoxin (and other cardiac glycoside)
C. the beta-Blocking agent (metoprolol, carvedilol) that is used for congested heart failure therapy through approval;
The associating of two or more hypotensive agents, most preferably, from a following different types of member:
Beta-Blocking agent:
Acebutolol, atenolol, bisoprolol, celiprolol, metoprolol, nebivolol (mebivolol), carvedilol (mixed type alpha-beta blocker), nadolol, oxprenolol, penbutolol, pindolol, Propranolol, timolol, betaxolol, carteolol
Calcium ion antagonist (calcium ion channel blocker):
Nifedipine, amlodipine, verapamil, diltiazem, nisoldipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, Manidipine
Thiazide-type diuretic (containing or do not contain isokalaemic diuretic such as triamterene, amiloride or spironolactone):
Hydrochlorothiazide, chlorothiazide, cyclopenthiazide, polythiazide, bendroflumethiazide, hydroflumethiazide, chlortalidone, indapamide, methyclothiazide, Mei Tuola hydrazone
Angiotensin converting enzyme inhibitor:
Captopril, Enalapril, lisinopril, ramipril, trandolapril, quinapril, perindopril, moexipril, benazepril, fosinopril
The Angiotensin Receptors blocker:
Losartan, valsartan, Candesartan, telmisartan, Eprosartan, irbesartan
Efficient (medullary loop) diuretic (containing or do not contain isokalaemic diuretic such as triamterene, amiloride or spironolactone):
Beautiful its Buddhist nun of furosemide, torasemide, etacrynic acid, cloth
The aldosterone antagonists diuretic:
Spironolactone, eplerenone
α-Zu Zhiji:
Doxazosin, terazosin, prazosin, indoramine, labetalol (mixed type alpha-beta blocker)
The maincenter alpha antagonist:
Clonidine, methyldopa
Imidazoline: moxonidine
Direct vasodilation:
Hydralazine, minoxidil
Adrenergic neuron blocking agent: guanethidine.
Should be understood that some associating, as beta-Blocking agent and diuretic, than other associating more preferably, as verapamil and beta-Blocking agent, or furosemide and hydrochlorothiazide.Other associating also is like this.
Except above-mentioned, many products are benefited from accurate separability, as are half-value dose, 1/4 dosage etc.Some outstanding examples more benefited than most of products comprise narrow therapeutic index medicine.The example of these medicines is that warfarin is received and other Coumarins, Levothyroxinnatrium and digoxin.Benefit from distinguishingly that to be configured to when wishing by other example of clean cut separation be vasoactive agent such as calcium ion antagonist and beta-Blocking agent.For example, if be not all, only active medicine in the dosage form of the present invention be prepared and be can be subsequently to the medicine of many above-mentioned relevant associatings can effectively by the present invention.Like this, many independent drug products can accurately separate from other by mode of the present invention; And the combination medicine product can be placed a subunit and be used as fixed dosage like this to unite and accurately separated jointly.
About above or the quantity of the subunit of any educational example that provides, be not intended to restriction.Be not intended to limit many examples about the dosage subunit associating of benefiting from this invention.Many other single preparations except above-mentioned those, can be prepared separately, or use the inventive method and other medicines co-formulated.
Produce
Preferred adhesion substance comprises, do not limit, below:
In addition, suitable adhesion substance can be selected from following tabulation:
As composite adhesives, can quote following specific example:
As the thermosetting resin binding agent, chemical reaction type urea resin, melmac, phenolic resins, epoxy resin, mylar, polyimide resin and similar resin.
As ger-bond, solvent vaporization type solvent-borne type vinyl acetate resin, emulsion-type vinyl acetate resin, vinyl chloride-vinyl acetate copolymer resins, nitrocellulose, propylene vinyl acetate copolymerized resin, ethylene-vinyl acetate copolymer resins, and similar resin; Chemical reaction type cyanacrylate, anaerobism acrylic resin, polyurethane resin and similar resin; Cooling (hot melt) type ethylene-vinyl acetate copolymer resins, polyamide, polyester, and similar resin; Pressure sensitive acrylic resin, and similar resin.
As synthetic rubber binder, solvent vaporization type chloroprene rubber, nitrile rubber, reclaimed rubber, latex, and rubber like; Chemistry-reaction type polyurethane rubber, and rubber like; Cooling (hot melt) type polystyrene-poly isoprene-polystyrene block copolymer, and analog; Pressure sensitive butyl rubber, Oppanol, silicones, and analog.
As the alloyed polymer binding agent, chemical reaction vinyl-phenolic aldehyde, rubber-phenolic aldehyde, epoxy radicals-phenolic aldehyde, nylon-epoxy, nitrile-epoxy, and analog.
As natural glue, can enumerate following specific example.
Solvent vaporization type starch, casein, dextrin, Radix Acaciae senegalis, and analog; Cooling (hot melt) type Colophonium, glue, Colophonium, and analog; Reach pressure sensitive conjugation polysaccharide, natural rubber, and analog.
As binding agent, can enumerate following specific example.
As rubber adhesive, tackifier, softening agent, antioxidant, and the mixture of analog and lactoprene.
As acryloid cement, the sintetics of acrylate and analog.
As silicon resin adhesive, produce material from silicone rubber and water emulsion build silicones, oligomeric build silicones and heat molten type silicones.
In addition, polyethers binding agent, polyurethane binder etc.In addition, may in band easy to use and die, process these binding agents.
As stickum, can enumerate following specific example with water generates viscosity.
As the polymer with hydroxy-acid group, it is the analog of compositing monomer that acrylic copolymer reaches with acrylic acid; And, have monovalent salt and two valency salt and similar sodium salt, potassium salt, magnesium salt, and calcium salt as the material that contains salt.
As cellulose ether, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, methylcellulose, crystal fibre element-sodium carboxymethyl cellulose, and similar substance.
As the natural tack material, mucoprotein, agar, gelatin, pectin, carrageenin, sodium alginate, tracasol, chitin, chitosan, traganth powder, and similar substance.
Molecular weight is 200,000 or more Polyethylene Glycol, and similar substance.
As stickum, can enumerate following specific example with organic solvent such as alcohol and analog generation viscosity.
Hydroxypropyl cellulose, hydroxypropyl emthylcellulose, ethyl cellulose, hydroxypropylmethyl cellulose phthalate, hydroxy methocel acetic acid-succinate, acrylic copolymer, Lac, wax, and analog.
Active prescription
Directly compacting is filled a prescription
In making the monolayer tablet of bonding connection subsequently, use following prescription.Use Manesty 16Station Beta Press (monolayer rotary tablet machine) to make amlodipine tablet and benazepril tablet.These two preparations are the mixture of powderss that can directly suppress.The two forms amlodipine preparation mixture and benazepril preparation mixture in Patterson-Kelly ＂ V ＂ blender in advance.Using 1/4 inch plane bevel edge tablet machine compressed tablets to make its hardness is 25 kilograms.The tablet weight of amlodipine tablet is that the tablet weight of 62.0mg and benazepril tablet is 54.0mg.It is as follows to contain each particle weight (mg) partly:
Amlodipine tablet formulation Mg.
Calcium phosphate dibasic anhydrous 51.13
Amlodipine benzenesulphonate 7.15
Carboxymethylstach sodium (Explotab
) 2.48
Magnesium stearate 0.93
FD﹠amp; C Blue#1 aluminum color lake
0.31
Amount to 62.00
Benazepril tablet formulation Mg.
Lactose 310 monohydrates 42.03
Benazepril hydrochlorate 9.00
Crospovidone 2.16
Magnesium stearate 0.54
FD﹠amp; C Red # 40 aluminum color lake
0.27
Amount to 54.00
The wet grain of fluid bed preparation
Use following two prescriptions to produce the wet grain that can be compressed to the monolayer tablet subsequently and can adhesively link together.
Wet grain all uses following fluidised bed granulator flow process to make.
1. by US20 hole sizer screening active pharmaceutical composition (API) (amlodipine or chlortalidone), starch 1500, Explotab and microcrystalline Cellulose.
2. by US30-hole sizer screening magnesium stearate.
3. all the components of weighing.Balance.
4. when stirring, by 150g starch 1500 being added to preparation 12% starch slurry in the 1100g water with Lightnin blender with propeller shaft.Mix 10min at least.During the granulation flow process, continue to stir.
5. 1/2 microcrystalline Cellulose, API, 22.5g Explotab and residue microcrystalline Cellulose are placed Mendel fluidized bed dryer/granulator that 20 liters of bowls and top-spray nozzle are installed.Before beginning spraying, mixed minimum 10 minutes.Parameter is set is:
Inlet temperature: 60 ℃ to 70 ℃
Spray rate: 25g/min is to 35g/min
Atomizing pressure: 1 crust
6. all starch 1500 slurries are sprayed on the blender.
7. dried particles makes its about 2% humidity.
8. use Comil mill-drying granule with 20 hole equivalent sieves.
9. the granule that will grind places 4 quarts of V-blenders and adds remaining 12.5g Explotab and mixed 5 minutes.
10. magnesium stearate is joined the V-blender and mixed 3 minutes.
Tablet is pressed on the monolayer rotary tablet machine at Manesty 16 station Beta Press.Use 1/4 inch plane bevel edge tablet tablet machine compressed tablets so that its hardness is that 20 kilograms are to 25 kilograms.The amlodipine tablet weight is that 60.0mg and Thalitone weight are 70mg.
Below provide and be used for producing the particulate prescription that can use at tablet of the present invention.
| Composition | %, wet grain | %, each tablet | Every tablet quantity |
| Amlodipine benzenesulphonate | 17.138 | 16.667 | 10 |
| Anhydrous calcium phosphate | 54.842 | 53.333 | 32 |
| Starch 1500 | 15.424 | 15.000 | 9 |
| Microcrystalline Cellulose PH102 | 10.282 | 10.000 | 6 |
| Carboxymethylstach sodium (in the granule) | 2.314 | 2.250 | 1.35 |
| Carboxymethylstach sodium (granule is outer) | - | 2.250 | 1.35 |
| Magnesium stearate | - | 0.500 | 1.35 |
| Water (being suitable for 12% starch slurry) | As Req’d | - | - |
| Amount to | 100％ | 100％ | 60mg |
| Composition | %, wet grain | %, each tablet | Every tablet quantity |
| Chlortalidone | 36.724 | 35.714 | 25 |
| Anhydrous calcium phosphate | 35.255 | 34.286 | 24 |
| Starch 1500 | 15.424 | 15.000 | 10.5 |
| Microcrystalline Cellulose PH102 | 10.283 | 10.000 | 7 |
| Carboxymethylstach sodium (in the granule) | 2.314 | 2.250 | 1.575 |
| Carboxymethylstach sodium (granule is outer) | - | 2.250 | 1.575 |
| Magnesium stearate | - | 0.500 | 0.350 |
| Water (being suitable for 12% starch slurry) | As Req’d | - | - |
| Amount to | 100％ | 100％ | 70mg |
The non-activity prescription
Directly compacting is filled a prescription
Making and adhesively being connected in subsequently in the monolayer tablet of other tablet, use following prescription.Use Manesty 16 Station Beta Press (monolayer rotary tablet machine) to make tablet.Three prescriptions are direct suppressible mixture of powderss.Mixture is preformed in Patterson-Kelly ＂ V ＂ blender.Using 1/4 inch plane bevel edge tablet machine compressed tablets to make its hardness is 20 kilograms-25 kilograms.The particulate weight (mg) that contains every kind of tablet is as follows:
Tablet 1
Mg.
Tablet 2Mg.
Calcium phosphate dibasic anhydrous 158.59
Magnesium stearate 2.79
PVP K-30
2.62
Amount to 164.00
Tablet 3Mg.
Lactose 316Fast-Flo 70.00
Microcrystalline Cellulose (Avicel PH102
) 24.00
Crospovidone 4.00
Silica sol 0.50
Hydrogenant vegetable oil 1.00
FD﹠amp; C Red# 40 aluminum color lake 0.50
The wet grain of fluid bed preparation
Use following two prescriptions to produce the wet grain of the non-activity that is compressed to the monolayer tablet subsequently.Use the wet grain of following fluidised bed granulator flow process manufacturing.
11. by the screening of US 20 hole sizers starch 1500, Explotab and microcrystalline Cellulose.
12. by US 30-hole sizer screening magnesium stearate.
The all the components 13. weigh.Balance.
14. when stirring, by 150g starch 1500 being added to preparation 12% starch slurry in the 1100g water with Lightnin blender with propeller shaft.Stirred minimum 10 minutes.During the granulation flow process, continue to stir.
15. 1/2 microcrystalline Cellulose, 22.5g Explotab and residue microcrystalline Cellulose are placed Mendel fluidized bed dryer/granulator that 20 liters of bowls and top-spray nozzle are installed.Before beginning spraying, mixed minimum 10 minutes.Parameter is set is:
Inlet temperature: 60 ℃ to 70 ℃
Spray rate: 25g/min is to 35g/min
Atomizing pressure: 1 crust
16. all starch 1500 slurries are sprayed on the blender.
17. dried particles makes its about 2% humidity.
18. use Comil mill-drying granule with 20 hole equivalent sieves.
19. the granule that will grind places 4 quarts of V-blenders and adds remaining 12.5g Explotab and mixed 5 minutes.
20. magnesium stearate joined the V-blender and mixed 3 minutes.
Tablet is pressed on the monolayer rotary tablet machine at Manesty 16 station Beta Press.Use 1/4 inch plane bevel edge tablet tablet machine compressed tablets so that its hardness is that 20 kilograms are to 25 kilograms.Tablet weight is 70mg.
Can use following prescription to make granule, but described granule production tablet subunit of the present invention.
The non-activity wet granular
| Composition | Each tablet percentage ratio | Each tablet quantity (mg) | Every lot number amount (mg) |
| Starch 1500 (colorcon) | 15.00％ | 10.5 | 150 |
| Microcrystalline Cellulose (Avicel PH102) (FMC) | 80.00％ | 56.0 | 800 |
| Carboxymethylstach sodium | 4.5％ | 3.15 | 45 |
| Magnesium stearate (Mallinckrodt) | 0.5％ | 0.35 | 5 |
| Water (non-final mixture part) | 1100 * | ||
| 100％ | 70 | 1000 |
Above-mentioned activity and non-activity prescription also are suitable for the capsule filler.This prescription need be adjusted to be fit to the amount of expection capsule filler.
For making the pharmaceutical dosage form that adhesively connects, can use the well-known technology compacting in tablet manufacturing field amlodipine tablet to make tablet by using a kind of above-mentioned prescription.Inert tablet can be used a kind of above-mentioned prescription manufacturing.A kind of being used in the above-mentioned preparation produced Thalitone according to standard technique.Binding agent, as, the medicinal glaze of Mantrose-Heauser #4 (Lac) 45/200 is used in two fields of conjugate action of inert tablet.Field of conjugate action and Thalitone (field of conjugate action) that the field of conjugate action of amlodipine tablet is connected to inert tablet are connected in another field of conjugate action of inert tablet.Before active tablet and inert tablet engagement, binding agent can or can not be applied to the field of conjugate action of active tablet.Allow tablet being with or without drying or dry in drying tube under applied pressure under the external condition.
Many other methods of production dosage form of the present invention can be suggested prescription that use provides above so that tablet or capsular production to be provided.According to the present invention, use well known by persons skilled in the art and will be developed, but in still undeveloped now many tablets and the capsule formula any, can produce almost countless dosage forms.
Lac solution, preferably scope is that 29% w/w can be used as binding agent to 36% w/w solid in comprising alcoholic acid solvent.The adjuvant device is dipped in the thorough blended Lac and Lac solution is applied to connecting the surface.The tablet subunit is connected to the tablet subunit; The capsule subunit is connected to capsule subunit and tablet subunit or capsule subunit and is connected by the connector between them.Be not intended to limit the quantity of subunit or connector.
The example that connects the method for dosage form subunit:
1. about 1ml Lac solution is applied to whole connections surface of tablet subunit.With regard to the tablet subunit, it connects any flat surface on the surperficial normally tablet subunit, but is not limited to this type of surface.When some or all solvents (alcohol) in being present in Lac solution evaporate, allow about 10 to 20 second flows to die, the tacky adhesion residue on the remaining tablet subunit.The connection surface of the second tablet subunit is contacted with the tacky surfaces of first subunit.The about 20 seconds Manual pressures through kicking the beam, subunit is fixed together, and makes it at air drying subsequently.
2. alternative method is included in about same time Lac solution is placed the connection surface of two subunits, manually light pressure is applied to two subunit last 20 seconds, and makes air-dry about 1 minute of dosage form so that solvent evaporation.
3. when capsule is connected to each other, can follow similar method and utilize connector (subunit) to connect tablet and tablet, capsule and capsule, and tablet and capsule, the production dosage form, wherein preformed tablet and capsule work as tablet subunit and capsule subunit subsequently.
Be not intended to limit the selection of Lac diluent, particular adhesive, time that the bonding connection subunit is exerted pressure and degree, make any solvent evaporation time, be connected the scope of the quantity etc. of subunit.The method of automatic or automanual bonding connection subunit is contained in the present invention especially.
Claims (20)
1. solid pharmaceutical dosage formulation, it comprises the subunit of a plurality of bonding connections and also comprises one or more following subunits:
A. (i) first inert tablet subunit and the (ii) second active subunit;
B. (i) has the first tablet subunit of pharmacology non-activity layer, and in this tablet subunit, described layer quality is at least the 20mg and (ii) second subunit;
C. be provided with the tablet subunit of separation marking; Or
D. (i) first tablet subunit and the (ii) second capsule subunit, it adhesively is connected on the described first tablet subunit.
2. solid pharmaceutical dosage formulation according to claim 1, it comprises two active subunits.
3. solid pharmaceutical dosage formulation according to claim 1, wherein all subunits comprise active component and the tablet subunit that is provided with separation marking.
4. solid pharmaceutical dosage formulation according to claim 3, wherein said separation marking comprises indentation.
5. solid pharmaceutical dosage formulation according to claim 2, it comprises the inert tablet subunit that adhesively is connected in two active subunits, and described active subunit connects with being not bonded to each other.
6. solid pharmaceutical dosage formulation according to claim 5, wherein said inert tablet subunit is provided with separation marking.
7. solid pharmaceutical dosage formulation according to claim 7, wherein said separation marking comprises indentation.
8. solid pharmaceutical dosage formulation according to claim 1, wherein said inert tablet subunit is provided with separation marking.
9. solid pharmaceutical dosage formulation according to claim 8, wherein said separation marking comprises indentation.
10. solid pharmaceutical dosage formulation according to claim 1, it comprises the active subunit with separation marking.
11. solid pharmaceutical dosage formulation according to claim 12, wherein said separation marking comprises indentation.
12. solid pharmaceutical dosage formulation according to claim 1, wherein said binding agent comprises Lac, pharmaceutically acceptable acrylic polymer or HYDROXY PROPYL METHYLCELLULOSE.
13. solid pharmaceutical dosage formulation according to claim 1, wherein all active subunits comprise identical a kind of medicine or multiple medicine.
14. solid pharmaceutical dosage formulation according to claim 1, wherein two active subunits comprise different a kind of medicines or multiple medicine.
15. the method with the described solid pharmaceutical dosage formulation segmentation of claim 1, it is not included in when dissolving and disconnects described dosage form, removes or disconnect the described binding agent that a plurality of subunits are linked together at tablet subunit place.
16. method according to claim 15, it is included in the separation marking place and disconnects.
17. method according to claim 16, wherein said separation marking comprises indentation.
18. method of using a part of active subunit of the described solid pharmaceutical dosage formulation of claim 1, described method is included in that active subunit place at first disconnects described pharmaceutical dosage form and subsequently to having its human patients that needs or other mammal or other animal to use randomly to comprise the described part of one or more its other subunits or part, and it is with after the described part of the described dosage form of intestinal absorption.
19. method of using the active pharmaceutical ingredient in the active subunit that is present in the solid pharmaceutical dosage formulation described in the claim 1, described method is included in that inert tablet subunit place disconnects described pharmaceutical dosage form and subsequently to having its human patients that needs or other mammal or other animal to use the part of the described dosage form that contains all or part of active tablet subunit and inert tablet subunit, and it is with after the described part of the described dosage form of intestinal absorption.
20. a method of making the described solid pharmaceutical dosage formulation of claim 1, it comprises:
(a) at first, the first active subunit or inert tablet subunit are used binding agent; And
(b) secondly, make the first active subunit or the inert tablet subunit that comprise binding agent contact the second active subunit or inert tablet subunit, it is bonded to each other, randomly that described first subunit and described second subunit is compressed together that it randomly is provided with binding agent so that described first subunit and described second subunit.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2005/047499 WO2007078290A1 (en) | 2005-12-30 | 2005-12-30 | Adhesively bonded dosage form |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101370483A true CN101370483A (en) | 2009-02-18 |
Family
ID=38228526
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005800525600A Pending CN101370483A (en) | 2005-12-30 | 2005-12-30 | Dosage form for adhesion connection |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1965772A1 (en) |
| JP (1) | JP2009522259A (en) |
| CN (1) | CN101370483A (en) |
| AU (1) | AU2005339699A1 (en) |
| BR (1) | BRPI0520830A2 (en) |
| CA (1) | CA2635566A1 (en) |
| IL (1) | IL192500A0 (en) |
| WO (1) | WO2007078290A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103167858A (en) * | 2010-07-19 | 2013-06-19 | 杜奥-戈公司 | Device and installation for joining at least two medicine capsules by adhesive bonding |
| CN106236715A (en) * | 2015-06-03 | 2016-12-21 | 南京三迭纪医药科技有限公司 | Pharmaceutical formulation and use thereof |
| CN110290781A (en) * | 2017-01-26 | 2019-09-27 | 南京三迭纪医药科技有限公司 | The dosage form of stomach and intestine privileged site control release |
| US11278499B2 (en) | 2015-06-03 | 2022-03-22 | Triastek, Inc. | Oral drug dosage form comprising various release profiles |
| US11571391B2 (en) | 2018-01-09 | 2023-02-07 | Triastek, Inc. | Oral drug dosage forms compromising a fixed-dose of an ADHD non-stimulant and an ADHD stimulant |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5009896A (en) * | 1989-10-04 | 1991-04-23 | Akzo N.V. | Multi-fractionable tablet structure |
| JPH069375A (en) * | 1992-04-10 | 1994-01-18 | Takeda Chem Ind Ltd | Dividable connected tablet |
| JP3048815B2 (en) * | 1993-12-27 | 2000-06-05 | 協和醗酵工業株式会社 | Method of processing tablet dividing line using laser beam |
| GB0027471D0 (en) * | 2000-11-08 | 2000-12-27 | Smithkline Beecham Plc | Processes |
| GB0102342D0 (en) * | 2001-01-30 | 2001-03-14 | Smithkline Beecham Plc | Pharmaceutical formulation |
| WO2003051339A1 (en) * | 2001-12-19 | 2003-06-26 | Sanwa Kagaku Kenkyusho Co.,Ltd | Release control type formed product |
| TW201240679A (en) * | 2004-03-12 | 2012-10-16 | Capsugel Belgium Nv | Pharmaceutical formulations |
| AU2005245028B2 (en) * | 2004-05-21 | 2010-12-09 | Accu-Break Technologies, Inc. | Pharmaceutical tablets having a relatively inactive segment |
| JP5046501B2 (en) * | 2005-08-18 | 2012-10-10 | 帝人ファーマ株式会社 | Tablets that hold multiple drugs separately |
-
2005
- 2005-12-30 WO PCT/US2005/047499 patent/WO2007078290A1/en active Application Filing
- 2005-12-30 BR BRPI0520830-0A patent/BRPI0520830A2/en not_active IP Right Cessation
- 2005-12-30 JP JP2008548483A patent/JP2009522259A/en active Pending
- 2005-12-30 EP EP05855981A patent/EP1965772A1/en not_active Withdrawn
- 2005-12-30 AU AU2005339699A patent/AU2005339699A1/en not_active Abandoned
- 2005-12-30 CN CNA2005800525600A patent/CN101370483A/en active Pending
- 2005-12-30 CA CA002635566A patent/CA2635566A1/en not_active Abandoned
-
2008
- 2008-06-29 IL IL192500A patent/IL192500A0/en unknown
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103167858A (en) * | 2010-07-19 | 2013-06-19 | 杜奥-戈公司 | Device and installation for joining at least two medicine capsules by adhesive bonding |
| CN103167858B (en) * | 2010-07-19 | 2014-09-10 | 杜奥-戈公司 | Device and installation for joining at least two medicine capsules by adhesive bonding |
| CN113171350A (en) * | 2015-06-03 | 2021-07-27 | 南京三迭纪医药科技有限公司 | Pharmaceutical dosage forms and uses thereof |
| CN108653221A (en) * | 2015-06-03 | 2018-10-16 | 南京三迭纪医药科技有限公司 | Pharmaceutical formulation and its use |
| CN108721242A (en) * | 2015-06-03 | 2018-11-02 | 南京三迭纪医药科技有限公司 | Pharmaceutical formulation and its use |
| CN109431965A (en) * | 2015-06-03 | 2019-03-08 | 南京三迭纪医药科技有限公司 | Pharmaceutical formulation and its use |
| CN108721242B (en) * | 2015-06-03 | 2021-03-02 | 南京三迭纪医药科技有限公司 | Pharmaceutical dosage forms and uses thereof |
| CN106236715B (en) * | 2015-06-03 | 2021-05-07 | 南京三迭纪医药科技有限公司 | Pharmaceutical dosage forms and uses thereof |
| CN106236715A (en) * | 2015-06-03 | 2016-12-21 | 南京三迭纪医药科技有限公司 | Pharmaceutical formulation and use thereof |
| US11278499B2 (en) | 2015-06-03 | 2022-03-22 | Triastek, Inc. | Oral drug dosage form comprising various release profiles |
| CN109431965B (en) * | 2015-06-03 | 2022-04-08 | 南京三迭纪医药科技有限公司 | Pharmaceutical dosage forms and uses thereof |
| CN113171350B (en) * | 2015-06-03 | 2023-05-26 | 南京三迭纪医药科技有限公司 | Pharmaceutical dosage forms and uses thereof |
| CN110290781A (en) * | 2017-01-26 | 2019-09-27 | 南京三迭纪医药科技有限公司 | The dosage form of stomach and intestine privileged site control release |
| US11571391B2 (en) | 2018-01-09 | 2023-02-07 | Triastek, Inc. | Oral drug dosage forms compromising a fixed-dose of an ADHD non-stimulant and an ADHD stimulant |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1965772A1 (en) | 2008-09-10 |
| BRPI0520830A2 (en) | 2009-05-19 |
| WO2007078290A1 (en) | 2007-07-12 |
| CA2635566A1 (en) | 2007-07-12 |
| AU2005339699A1 (en) | 2007-07-12 |
| IL192500A0 (en) | 2009-02-11 |
| JP2009522259A (en) | 2009-06-11 |
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