TWI426897B - Barrier for capsule, capsule using the same, and method of filling capsule - Google Patents

Description

Barrier layer for use in capsule, capsule using same, and capsule filling method

The present invention relates to a method of filling a plurality of homogeneous substances into a capsule using a filling device for a capsule.

Fig. 1A is a shape of a generally known capsule which is composed of a cylindrical body and a cylindrical lid body. The outer shape of the body is smaller than the outer shape of the lid body, but the body can be defined by a cylindrical lid body having a large outer shape. In Figure 1A, the body is defined by a smaller profile. During the loading of the capsule into the filling, the empty capsule temporarily combined with the body will precede the hopper, and the fixed number will be released from the feeding hopper and the cover will be separated from the body. After the body is loaded with the drug, the cover is combined with the cover so as not to be separated from the body. Depending on the situation, for example, the lid body and the body may be sizing and sealed for drying purposes according to the purpose of deodorization, leakage prevention, and oxygen penetration prevention.

There are various devices on the market for filling drugs or other substances in capsules, and capsule filling as described above can be performed. There are fewer problems when the filling is a powdery solid or granule, but when filling a semi-solid or liquid, especially when filling two semi-solids or liquids having medicinal properties, the following problems are solved in order to maintain the intended efficacy. That is, the upper interface of the first filled semi-solid or liquid form filling should be horizontal and stable, and will not mix with the semi-solid or liquid filled in the next step. If mixed, drug interaction will occur. The problem of expected efficacy is not available.

On the other hand, once the surface of the filled semi-solid or liquid is foamed, or not in a fixed shape, for example, when the interface is close to horizontal and is inclined with respect to the horizontal, and the interface is smooth and relatively smooth, the surface At the time of foaming, the area of the surface of the drug changes greatly, and the time taken for the dissolution of the drug also changes to obtain the problem of the intended drug effect.

In order to solve the above problems, the present invention provides a multilayer filled capsule which prevents mixing or/and action of a filled drug and a method of manufacturing the same.

It is an object of the present invention to provide a multilayer filled capsule and a method of producing the same that can form a capsule containing the same drug having different elution characteristics.

An object of the present invention is to provide a multilayer filled capsule and a method for producing the same, which can prevent a change in the elution characteristics of a filled drug.

Another object of the present invention is to provide a multilayer filled capsule and a method of manufacturing the same that can form a capsule containing different drugs.

Another object of the present invention is to provide a multilayer filled capsule and a method of manufacturing the same that prevent interaction of the filled drug.

The present invention provides a multilayer filled capsule. The multi-layer filling capsule comprises a body and at least one cover body, wherein the body has at least one opening and an inner space, and the cover body is detachably coupled with the body to close the opening; further, the body further comprises a connection with the inner wall surrounding the inner space. Barrier layer. The barrier layer is composed of a stable component and partitions the internal space into a first partition space and a second partition space; the first partition space and the second partition space and respectively have a first homogeneous substance and a second homogeneous substance. That is, the inner space of the capsule body will be formed with three filling units/filling layers. In addition, the first homogeneous substance and the second homogeneous substance may be in the form of a liquid, a solid or a semi-solid under normal temperature and storage conditions, wherein the liquid comprises a homogeneous liquid and a suspension; the solid comprises a solid block, a microcapsule, a pellet, Or a powdery solid such as a powder. The characteristics of a solid block have a liquid form or a semi-solid form above its melting point temperature.

The method for manufacturing a multi-layered filled capsule of the present invention comprises the steps of: the capsule is housed in the feeding hopper in a state in which the lid body is combined with the body; the capsule taken out from the feeding hopper is directionally restricted so that the opening of the body is horizontally upward; Separating from the body such that the upper end of the capsule is open; removing the poorly-separated capsule and the body-deficient capsule for filling; and filling the first homogeneous substance, comprising heating the first homogenate to make it a fluid or semi-solid Forming to facilitate filling; cooling the first homogeneous substance, comprising curing the first homogeneous substance having fluidity during filling; filling the barrier layer, comprising determining a proportion of the barrier layer component mineral oil and paraffin wax to set an appropriate melting point of the barrier layer, And heating the barrier layer component to make it fluid and convenient for filling, and the temperature of the barrier layer after heating does not cause the first homogeneous substance solidified in the previous step to remelt; cooling the barrier layer to solidify; filling the second homogeneous substance, It comprises heating the second homogenate to make it a liquid or semi-solid form with fluidity for easy filling and heating The homogenate temperature does not cause the barrier layer to be cured in the previous step to remelt; the second homogenate is cooled, which comprises solidifying the second homogenate with fluidity during filling; the lid body is combined with the body to complete the capsule manufacturing; and finally the capsule is discharged And exclude capsules that are not filled or incompletely filled and cleaned. In addition, a barrier layer connected to the inner wall may be formed in the inner space of the capsule, and the inner space is first divided into a first separation space and a second separation space without a filling, and then respectively in the first separation space. And the second partition space is filled with the first homogeneous substance and the second homogeneous substance.

The present invention provides a multilayer filled capsule filled with the same drug or different drugs having different elution characteristics. In order to stabilize the drug during storage of the capsule and obtain the expected drug effect, and to ensure that the drug does not interact with each other during the filling process, the multi-layered filled capsule of the present invention comprises a barrier which is prepared by the stability component during the process of manufacturing the capsule. Floor. In detail, as shown in FIGS. 1A-1B, the capsule 1 of the present invention comprises a body 2 and at least one cover 3; wherein the body has at least one opening 4 and an internal space 5, and the cover 3 preferably has a body 2 The large diameter is detachably combined with the body 2 to close the opening 4; further, the body 2 further comprises an inner wall surrounding the inner space, the barrier layer is connected to the inner wall and divides the inner space into the first separation space and the second Separation space (not shown). The thickness of the barrier layer preferably ranges from 5% to 25% of the total length of the body. The barrier layer material is a non-hazardous ingredient that is biologically innocuous. After the barrier layer enters the digestive tract with the capsule, the digestive tract environment can melt, decompose, or directly vent the barrier layer formed by the modulation of the components. In a preferred embodiment of the present invention, the barrier layer component is mineral oil and/or paraffin wax, wherein the weight ratio of the mineral oil to the paraffin component is between 0 and 4, that is, the mineral oil content in the barrier layer component. It may be at least 0; in other words, the barrier layer component must contain paraffin wax so that the barrier layer has a solid form under normal temperature or capsule storage conditions. The ratio of mineral oil to paraffin affects the melting point of the barrier layer, and its relationship with the capsule manufacturing method will be described in detail later.

As shown in FIG. 4, the first partitioning space 61 and the second partitioning space 62 respectively accommodate the first homogeneous substance 51 and the second homogeneous substance 52, that is, the barrier layer 50 separates the first homogeneous substance 51 and the second homogeneous substance 52; In other words, the inner space of the capsule body has three filling units/filling layers. In a preferred embodiment, the first homogeneous substance and the second homogeneous substance are drugs. The first homogeneous substance or the second homogeneous substance may be in the form of a liquid, a solid or a semi-solid under normal temperature and storage conditions, wherein the liquid comprises a homogeneous liquid and a suspension; the solid comprises a solid block, a microcapsule, a granule, or a powdery solid. For example, a powder; a semi-solid is a viscous fluid, and its flow force is slower than that of a fluid that is also a fluid. The solid block is characterized by a liquid form or a semi-solid form at a temperature above normal temperature, and preferably above 35 °C. When the first homogeneous substance or the second homogeneous substance is in the form of a solid block at normal temperature and under storage conditions, the composition of the first homogeneous substance or the second homogeneous substance is further included at a temperature higher than normal temperature, and preferably higher than 35 ° C. a hot-melt excipient in a liquid form or a semi-solid form under temperature conditions; wherein the melting point of the first homogeneous substance is greater than the melting point of the barrier layer, and the melting point of the barrier layer is greater than the melting point of the second homogeneous substance.

The invention also comprises a filling method for manufacturing a multi-layer filling capsule, wherein the filling of the multi-layer filling capsule is completed by a capsule filling device, which can complete the capsule filling/manufacturing in an intermittent driving manner and/or a continuous driving manner, and is suitable for the disc Capsule holder in the way, chain link mode. Please refer to the flow chart of the embodiment shown in FIG. 2 and the schematic diagram of FIG. 3-4. Step 810 includes: the capsule is received in the feeding hopper in a state in which the cover body and the body are combined. Step 820 includes directionalally limiting the capsules removed from the hopper. In order to have the first homogenate, the barrier layer and the second homogeneous substance filled have a fixed shape and have a small contact surface with adjacent fillers to ensure a drug elution effect, in step 820, the direction of the capsule 1 is limited. Preferably, as shown in FIG. 4, the axis of the body 2 and the cover 3 is perpendicular to the horizontal plane, and the opening is horizontally upward; thus, the interface of the filler is optimally parallel to the opening and adjacent to each other. There will be minimal contact or minimum surface between the fillings. Wherein, the direction limitation of the capsule can be achieved by an inductive device such as a laser sensor, for example, the laser sensor can measure the positive or negative direction of the capsule, and if the capsule is reversed, the capsule will correct the disk when passing the direction. Reverse to positive, if the capsule is positive, the capsule will not have any action when correcting the disc through the direction. Step 830 includes separating the lid of the capsule from the body such that the upper end of the capsule is open. Next, step 840 is to exclude the capsule with poor separation and the capsule with defective body. In the normal machine operation, the capsule is separated into a cover body and a body in step 830. However, if the capsule is poorly separated and cannot be separated in this step, in step 840, the unseparated capsule will be mechanically actuated. The ejector pin is ejected to the collection box of the defective capsule; in the other case, the capsule is a defective capsule with only the body remaining or only the cover remaining, and the capsule is measured by two laser sensors: one of the sensors It is used to detect the capsule body, and the other is used to detect the capsule cover. The two sensors need to detect the cover and the body of the capsule at the same time, and the machine will proceed to the next step (ie, step 850); When only one of the sensors detects a capsule, the machine will stop until the defective capsule is manually removed before continuing to operate the machine.

Step 850 includes filling the first homogeneous mass. Wherein, the first homogeneous substance 51 preferably has a liquid or semi-solid form at a temperature higher than normal temperature, and preferably higher than 35 ° C, and is a solid block at a temperature lower than 35 ° C or at least when the temperature is lowered to a normal temperature. To avoid mixing when filling the next layer of filling (ie, barrier layer); wherein the first homogeneous substance is filled by the liquid and semi-solid flow by heating the first homogeneous substance to a liquid or semi-solid form Into the capsule. For example, if the first homogeneous substance has a melting point of A ° C and the surface can be solidified into a solid block when cooled to at least A ° C, the step 850 further includes a first homogeneous substance 51 having a filling temperature of A ° C or higher, at this time, The homogeneous substance 51 has fluidity and is easy to be filled. Step 855 includes cooling the first homogeneous mass. In the example of step 850, the temperature of the first homogeneous substance 51 above the temperature A °C at the time of filling is lowered to below a °C. The cooling means includes, but is not limited to, blowing air or cold air into the capsule body, the capsule body holder or the first homogeneous substance 51 in a filled liquid or semi-solid form to cool and speed up the curing. In addition, an external cooling device may be provided, for example, the capsule holder is directly cooled by cold coal, and the capsule body and the first homogeneous substance 51 are cooled. On the other hand, if the first homogeneous substance 51 is not required to be filled by heating, that is, it is the same form when it is filled and under normal temperature and/or storage conditions, for example, it is granular when filled, and after the capsule is formed. That is, when it is contained in a capsule in a pellet form, step 855 may not be performed. Upon completion of steps 850-855, a first filling unit/filling layer is formed.

Step 860 includes filling the barrier layer and forming a first separation space 61 filled with the first homogeneous substance 51 and a second separation space 62 not yet filled. The barrier layer is preferably used in a thickness of 5% to 25% of the total length of the body after the barrier layer is formed, but is not limited thereto. Further, at the time of filling, the barrier layer is in a liquid or semi-solid form having fluidity for easy filling. As mentioned above, the barrier layer component is preferably mineral oil and/or paraffin wax, wherein the weight ratio of mineral oil to paraffin component is between 0 and 4. When the barrier layer component comprises 100% paraffin wax, the barrier layer at this time has the highest melting point, that is, the melting point ranges from 60 to 65 ° C; when the barrier layer containing the 100% paraffin component is heated to 60 to 65 ° C At the time, the barrier layer will undergo a phase change with a liquid or semi-solid morphology. As the proportion of mineral oil increases, the melting point of the barrier layer decreases, so that the temperature required to bring the barrier layer into a liquid or semi-solid form can be less than 60 to 65 °C. Thus, step 860 further includes determining the melting point of the barrier layer and the proportion of mineral oil and/or paraffin used. Furthermore, as described above, the purpose of the barrier layer is to separate the first homogeneous substance 51 and the second homogeneous substance, and to fill after the first homogeneous substance 51 is filled. Since the barrier layer is preferably filled on the surface of the first homogeneous substance 51 which has been solidified into a solid block, and the barrier layer during filling is in a liquid or semi-solid form, the melting point B ° C of the barrier layer must be less than A ° C to avoid filling barrier. At the time of the layer, the temperature of the barrier layer re-dissolves the first homogeneous substance 51 whose surface has solidified. That is, the melting point of the barrier layer is lower than the melting point of the first homogeneous substance, and the ratio of the mineral oil to the paraffin component is determined according to the melting point range; wherein B°C is preferably greater than normal temperature and/or storage temperature to prevent barrier The layer melts under normal temperature and/or storage conditions to lose barrier properties or to be mixed with other layer fillers. Further, in the filling method, in order to prevent the surface of the previously filled filler from being roughened by the pressure caused by, for example, the filling of the barrier layer during the filling of the filling machine nozzle, the capsule manufacturing method of the present invention and the capsule filling device for performing the capsule manufacturing The discharge from the nozzle is caused to touch the inner wall 7 of the capsule, and the discharge pressure is lowered to perform the filling operation. That is, as shown in FIG. 5, the filling barrier layer is preferably formed by spraying a barrier layer component at a discharge point R of the inner wall 7, between the release point R and the top of the first homogeneous substance 51 contained in the inner space 5. The distance d is between 2 mm and 3 mm, and the angle between the spray line (arrow L) and the radial direction of the inner wall 7 of the spray point S and the release point R is preferably 10 Between ° and 40 °.

Step 865 includes cooling the barrier layer. The purpose of the cooling is such that the barrier layer preferably has a solid form to prevent the fluid-like barrier layer from easily mixing with the next layer (i.e., the second homogeneous material) when it is filled. Therefore, it is necessary to lower the temperature of the barrier layer at a temperature of B ° C or higher at the time of filling to below b ° C. When the temperature of the barrier layer is at least below b ° C, the surface can be solidified into a solid block. The cooling method is as described above, and will not be described herein. Upon completion of steps 860-865, a second filling unit/filling layer is formed.

Step 870 includes filling a second homogeneous mass. Wherein, (1) a second homogeneous substance 52 in a solid form, for example, a microcapsule, a granule, or a powdery solid, or (2) a second homogeneous substance in a liquid or semi-solid form may be filled. Wherein, the second homogeneous substance 52 in a liquid or semi-solid form upon filling may have a liquid or semi-solid form (2a) under normal temperature or storage conditions; or the second homogeneous substance 52 is a liquid liquid only when filled. Filling in a semi-solid form, but solidifying into a solid block (2b) under normal temperature or storage conditions, that is, the second homogenate 52 is liquid at a temperature higher than normal temperature and preferably higher than 35 ° C. Or semi-solid form.

For example, when the second homogeneous substance 52 belongs to the above (2b) and its melting point is C ° C, the step 870 further includes a second homogeneous substance 52 having a filling temperature of C ° C or higher; and further, due to the second homogeneous substance Preferably, 52 is filled on the surface of the barrier layer 50 which has been solidified into a solid form. Therefore, the melting point C°C of the second homogeneous substance 52 must be less than B°C to avoid the temperature of the second homogeneous substance 52 from curing when the filling is completed. Layer 50 is remelted. That is, the melting point of the second homogeneous substance 52 is lower than the melting point of the barrier layer 50. At this time, by integrating step 850, step 860, and step 870, it can be known that A ° C > B ° C > C ° C, that is, the higher melting point must be filled first. Take the example of filling a three-layer filled capsule of Zaleplon. The three-layer filled zaleplon is a dosage form containing two layers of drug-containing layers, namely a first homogeneous substance and a second homogeneous substance, and a layer of a drug-free barrier layer, wherein the barrier layer component is paraffin, and the two layers The drug layer is a solid block at normal temperature. The filling temperature of the first homogeneous substance is 75-80 ° C, and the temperature is obtained to make the layer better and easy to fill; the composition of the barrier layer is 100% paraffin wax, and the filling temperature is about 60-65 ° C; The filling temperature of the two homogeneous substances is 55 to 60 °C. Therefore, in order to achieve the melting point of the first homogeneous substance, the barrier layer, and the second homogeneous substance, the step 850, the step 860, and the step 870 also include heating the first homogeneous substance, the barrier layer or the second homogeneous substance, and The heating temperature range is between normal temperature and 80 ° C, that is, 25 ° C to 80 ° C. In addition, the filling method is the same as the foregoing, and will not be described herein.

Step 870 is followed by step 875 of selectively cooling the second homogeneous. Preferably, the second homogenate 52 is cooled to ambient temperature or to a suitable storage temperature. Upon completion of steps 870-875, a third filling unit/filling layer is formed. Step 880 includes: combining the cover and the body to complete the manufacture of a capsule having three filling units/fill layers. Step 890 includes discharging the capsule and removing the capsule that is not filled or incompletely filled. That is, the capsule passing through step 880 enters a detecting device such as a weight detecting device in step 890, and when the weight of the capsule is not within the specification, the capsule is automatically excluded; thereby distinguishing the filling completely and not filling Or fill the incomplete capsule and drain the latter two.

Therefore, the multi-layered filled capsule of the present invention separates the first homogeneous substance 51 and the second homogeneous substance 52 by the stability barrier layer 50, and in the preferred embodiment, the first homogeneous substance 51 and the second homogeneous substance 52 are contained in the drug substance. Ingredients. The separation of the barrier layer 50 prevents changes or interactions of the elution characteristics caused by the interaction between the drugs, for example, the formulation components penetrate each other due to the difference in concentration, thereby changing the intended drug effect. Furthermore, the method of manufacturing the multilayer filled capsule of the present invention further ensures that the filling of the barrier layer does not have an additional effect on the first homogeneous substance 51 or the second homogeneous substance 52 during the filling process.

In other embodiments of capsule filling, as shown in Figures 6A-6B, the barrier layer 50 may be filled first to directly divide the interior space into two. At this time, unlike the above embodiment, the first homogeneous substance and the second homogeneous substance are all filled from the same opening. The capsule 1 of the present embodiment includes an opening 4 and an opening 4', and a lid body 3 and a lid body 3' which are detachably coupled to the body 2, respectively, corresponding to the opening 4 and the opening 4'. The first homogeneous substance 51 and the second homogeneous substance 52 are filled into the internal space by the opening 4 and the opening 4', respectively; therefore, the two direction restricting steps are performed in this embodiment. As shown in FIGS. 7A-7B, step 910 includes: the capsule is received in the feeding hopper in a state in which the lid body is coupled to the body; and step 920 includes: separating at least one lid body and removing the capsule having poor separation. Step 930 includes filling the barrier layer. The barrier layer may be filled in such a manner as to directly form a barrier layer connected to the inner wall in the inner space, or may be disposed in front of the inner space, for example, a temporary bracket (not shown), and the bracket is used as an auxiliary to fill the barrier. Floor. Basically, the filling of this embodiment is still required to be filled according to the principle in the above embodiment, that is, the higher melting point is filled first; and, since the barrier layer is filled first in this embodiment, if the first homogeneous substance and the second homogeneous substance are All must be heated to be melted into a liquid or semi-solid to fill, then the melting point of the first homogeneous substance and the second homogeneous substance must be less than the melting point of the barrier layer. Since the ratio of the mineral oil and the paraffin in the barrier layer component affects the melting point of the barrier layer, step 930 further comprises determining the melting point of the barrier layer and the ratio of mineral oil and/or paraffin according to the melting points of the first homogeneous substance and the second homogeneous substance. Further, similarly, the melting point of the barrier layer is preferably greater than normal temperature and/or storage temperature to prevent the barrier layer from melting to lose the barrier function or to be mixed with the layer filler.

Step 935 includes cooling the barrier layer. Wherein, if a temporary bracket is used in step 930, the temporary bracket is removed from the interior space when step 935 is completed or before completion. Step 940 includes: performing a direction restriction. The direction in which step 940 is performed is limited to the first directional restriction in this embodiment, such that the axis of the body is perpendicular to the horizontal plane and the opening is horizontally upwards in preparation for the next step. Step 950 includes: filling the first homogeneous substance; step 955 includes: cooling the first homogeneous substance; and step 960 includes: combining the cover body and the body and performing direction limitation. Figure 7A Continue with Figure 7B . Step 965 includes separating another cover. The direction in step 960 is limited to the second direction limitation of the embodiment, and the purpose is to adjust the direction of the capsule so that another cover body is separated from the body (step 965), and the other cover body is another. The opening will face the appropriate direction, for example horizontally upwards, to accept the filler. Step 970 includes: filling a second homogeneous substance; step 975 includes: cooling the second homogeneous substance; and step 980 includes: combining another cover body and the body. Step 990 includes discharging the capsule and removing the capsule that is not filled or incompletely filled. Therefore, the filling sequence of the first homogeneous substance and the second homogeneous substance may be in accordance with the foregoing principles. In this embodiment, the manner of providing the barrier layer in the body first provides another option of filling the first homogeneous substance and the second homogeneous substance. . For example, when the first homogeneous substance or the second homogeneous substance is microcapsules, granules, powdery solids, or semi-solid, liquid under filling and normal temperature/storage conditions, this embodiment is applicable to, for example: A homogeneous substance is a liquid, a semi-solid and the second homogeneous substance is a microcapsule, a granule, or a powdery solid; or a filling when the first homogeneous substance and the second homogeneous substance are both liquid or both are semi-solid. This method does not require the filling of a liquid or semi-solid barrier layer on microcapsules, granules, powdered solids, semi-solids, or liquid surfaces (not easy to perform). Further, in the first embodiment, the first homogeneous substance is a solid and the second homogeneous substance is a solid or a semi-solid, and the filling of the liquid can also be carried out in the present embodiment.

The present invention has been described by the above-described related embodiments, but the above embodiments are merely examples for implementing the present invention. It must be noted that the disclosed embodiments do not limit the scope of the invention. On the contrary, modifications and equivalents of the spirit and scope of the invention are included in the scope of the invention.

1. . . capsule

2. . . Ontology

3. . . Cover

3’. . . Cover

4. . . Opening

4’. . . Opening

5. . . Internal space

50. . . Barrier layer

51. . . First homogenate

52. . . Second homogenate

61. . . First separation space

62. . . Second separation space

7. . . Inner wall

810. . . The capsule is housed in the feeding hopper in a state in which the lid body is coupled to the body

820. . . Limit the direction of the capsule taken out of the feed hopper

830. . . Separating the cover of the capsule from the body

840. . . Excludes poorly isolated capsules and capsules with defective bodies

850. . . Filling the first homogeneous substance

855. . . Cooling the first homogeneous substance

860. . . Filling barrier

865. . . Cooling barrier

870. . . Filling the second homogeneous substance

875. . . Cooling the second homogeneous substance

880. . . Combined with cover and body

890. . . Discharge the capsule and exclude capsules that are not filled or incompletely filled

910. . . The capsule is housed in the feeding hopper in a state in which the lid body is coupled to the body

920. . . Separating at least one cover and removing the poorly separated capsule

930. . . Filling barrier

935. . . Cooling barrier

940. . . Direction restriction

950. . . Filling the first homogeneous substance

955. . . Cooling the first homogeneous substance

960. . . Combine the cover body with the body and restrict the direction

965. . . Separate another cover

970. . . Filling the second homogeneous substance

975. . . Cooling the second homogeneous substance

980. . . Combine another cover and body

990. . . Discharge the capsule and exclude capsules that are not filled or incompletely filled

1A-1B are schematic views of a capsule of the present invention and prior art;

2 is a flow chart of an embodiment of a method for manufacturing a multilayer filled capsule of the present invention;

3 is a schematic view showing an embodiment of a method for manufacturing a multilayer filled capsule of the present invention;

Figure 4 is a schematic view showing a simplified embodiment of the method for manufacturing the multilayer filled capsule of the present invention;

Figure 5 is a partial schematic view showing an embodiment of a method for manufacturing a multilayer filled capsule of the present invention;

6A-6B are schematic views showing another embodiment of a method for manufacturing a multi-layer filled capsule according to the present invention;

7A-7B are detailed flow diagrams of another embodiment of the method of making a multilayer filled capsule of the present invention of Figs. 6A-6B.

810. . . The capsule is housed in the feeding hopper in a state in which the lid body is coupled to the body

820. . . Limit the direction of the capsule taken out of the feed hopper

830. . . Separating the cover of the capsule from the body

840. . . Excludes poorly isolated capsules and capsules with defective bodies

850. . . Filling the first homogeneous substance

855. . . Cooling the first homogeneous substance

860. . . Filling barrier

865. . . Cooling barrier

870. . . Filling the second homogeneous substance

875. . . Cooling the second homogeneous substance

880. . . Combined with cover and body

890. . . Discharge the capsule and exclude capsules that are not filled or incompletely filled

Claims (27)

A barrier layer for use in a capsule comprising a mineral oil and a paraffin having a weight ratio between 0 and 4, and causing a phase change in response to a change in temperature such that the interior of the capsule is a space or two compartments . A capsule comprising: a body having at least one opening and an inner space; at least one cover detachably coupled to the body to close the opening; and a barrier layer disposed in the body and subject to temperature changes Generating a phase change to cause the capsule to have the internal space, or separating the internal space into a first separation space and a second separation space; wherein the barrier layer component comprises mineral oil and paraffin, and the weight ratio of mineral oil to paraffin is Between 0 and 4. The capsule of claim 2, wherein the capsule has two openings and two covers, the two cover systems corresponding to the two openings, and detachably coupled to the body to close the two An opening. The capsule of claim 2, wherein the first compartment contains a first homogeneous substance and the second compartment contains a second homogeneous substance. The capsule of claim 4, wherein the first homogeneous substance or the second homogeneous substance is at room temperature in a solid selected from the group consisting of a solid block, a powdery solid, a particulate solid, and a microcapsule. The capsule of claim 5, wherein the solid block has a liquid or semi-solid form at a temperature above 35 °C. The capsule of claim 6, wherein the first homogeneous substance or the capsule The second homogenate further comprises at least one hot melt excipient which is in a liquid or semi-solid form at a temperature above 35 °C. The capsule of claim 4, wherein the first homogeneous substance or the second homogeneous substance is in the form of a liquid at room temperature. The capsule of claim 8 wherein the liquid comprises a suspension. The capsule of claim 4, wherein the first homogeneous compound or the second homogeneous compound is semi-solid at room temperature. The capsule of claim 6, wherein a relationship between a melting point of the first homogeneous substance, a melting point of the barrier layer, and a melting point of the second homogeneous substance is a melting point of the first homogeneous substance greater than the barrier layer a melting point, and a melting point of the barrier layer is greater than a melting point of the second homogeneous substance. The capsule of claim 6, wherein the relationship between the melting point of the first homogeneous substance, the melting point of the barrier layer, and the melting point of the second homogeneous substance is that the melting point of the barrier layer is greater than the first homogeneous substance. The melting point and the melting point of the second homogeneous substance. The capsule of claim 3, wherein the barrier layer has a thickness of from 5% to 25% of the total length of the body. A capsule filling method comprising the steps of: providing a capsule comprising a body and at least one cover, the body comprising at least one opening and an inner space; filling a first homogeneous substance in the inner space; filling a barrier layer The barrier layer separates the inner space; fills a second homogeneous substance in the inner space; and combines the body with the at least one cover; wherein the first homogeneous substance and the second homogeneous substance are isolated by the barrier layer, And The barrier layer component comprises mineral oil and paraffin wax; the weight ratio of mineral oil to paraffin wax is between 0 and 4. The method of claim 14, further comprising limiting the orientation of the capsule such that the axis of the body and the cover are perpendicular to a horizontal plane and the at least one opening is horizontally upward. The method of claim 14, further comprising separating the body and the cover after the step of providing the capsule to expose the opening. The method of claim 14, wherein the first homogenate filling step, the barrier layer filling step or the second homogenate filling step further comprises heating the first homogeneous substance, the barrier layer, or the first The homogenizer is such that the first homogeneous substance, the barrier layer or the second homogeneous substance assumes a liquid or semi-solid form. The method of claim 17, wherein the heating temperature ranges between 25 ° C and 80 ° C. The method of claim 17, wherein the first homogenate filling step, the barrier layer filling step, and the second homogenate filling step further comprise cooling the first homogeneous substance, the barrier layer, or the first The homogenizer is such that the first homogeneous substance, the barrier layer or the second homogeneous substance assumes a solid or semi-solid form. The method of claim 14, wherein the barrier layer filling step comprises separating the internal space into a first separation space and a second separation space, and the first separation space and the second separation space are respectively filled. There is the first homogeneous substance and the second homogeneous substance. The method of claim 14, further comprising confirming whether the capsule is defective. The method of claim 14, further comprising discharging the combination The capsule is finished. The method of claim 22, wherein the step of expelling the bonded capsule further comprises excluding the capsule that is not filled or incompletely filled. The method of claim 14, wherein the barrier layer has a thickness of from 5% to 25% of the total length of the body. The method of claim 14, wherein the barrier layer filling step further comprises spraying the barrier layer at a release point of the inner wall to form the barrier layer on the first homogeneous surface, and the releasing The distance between the point and the top of the first homogenizer is between 2 mm and 3 mm. The method of claim 25, wherein in the step of spraying the barrier layer, the angle between the spray line and the radial direction of the spray line and the release point is in the range of 10 Between ° and 40 °. The method of claim 19, wherein the filling sequence between the first homogenate filling step, the barrier layer filling step or the second homogenate filling step is the first homogeneous substance, the barrier layer And the higher melting point of the second homogeneous substance is filled first.