200823110 九、發明說明： 【發明所屬之技術領域3 本發明係與容器的密封作用有關。舉例來說，其係與 從聚合物圓盤所形成的容器的密封作用有關，其中該容器 5 包含有内含係為粉末形式之藥學配方的藥物封裝。 C先前技術3 使用熱及/或壓力來將一鋁箔層合薄片黏接成一聚合 物容器，係為一種已被充份發展來將藥物封裝密封，以對 抗例如水氣穿透之外界環境的污染的方法。該密封作用係 10 藉著將一層合至該鋁箔層合薄片的熱密封聚合物薄片，熔 接至該容器的聚合物表面内，並施加壓力以使得該熱密封 聚合物與該容器的一熔融或軟化層融合，並此將該容器的 鋁箔附接。該密封作用的品質係依據在整個的該密封區域 上，該熱密封聚合物被充分地融合到該容器的程度而定。 - 15 雖然該鋁箔可以提供一實質上充份的水分障壁作用， 然而對於該水氣滲透作用並沒有完全的不通透性之層合片 的熱密封層，會提供一個水氣可以到達該容器的内含物 (舉例來說一個藥物產品）之通路。然而，當該熱密封層係較 薄且在該層次暴露於周圍環境下與該等内含物的表面之間 20 距離夠長時，穿透該熱密封層的水氣可以被減少至一可接 受的程度。 該密封可以使用一熱滾筒或一熱的平面板件來形成。 其所使用的溫度和接觸時間係足以使得該容器的接觸表面 之熱密封層和薄層溶化。所施加的壓力然後將二個溶化的 5 200823110 層次融接在一起並使得該經熔化的材料在該接觸面積上流 動離開任何-點，直到整個的密封面積觀合在一起。直 可以痛保在整個的密封面積中形成一良好密封。 然而，有一些與此一已知方法有關的問題。第一，該 方法係不適合用於所有類型的容器中。第二，該熱密· 合物的薄層無法應付在容器密封表面的最終之相對較大偏 差或加工不兀王，並且第三，該密封的完整性可能會被在 該容器的密封表面上或是該層次之熱密封層上帶有的污染 物(舉例來說，藥物粒子)所危害。 10 15 不適用於上述之傳統密封方法一種容器類型係被描述 於W〇 03/015857、wo 03/0664胸⑽ 〇5/002654。此々 器包含有一其中形成有數個穿過該圓盤的孔洞之環狀； 盤’以使得該等孔洞會環繞著該圓盤的中心轴而形成 形陣列。在每個孔洞都容納了—被恰 圓 洞裡面之藥物封裝，藉此該藥 二=該孔 而移出該孔洞。該封裝可以包含=二被相對於该圓盤 式的藥學配方。為了要保護哕、、i八/#1±之粉末形 主t 认舌性物質’該圓盤在复之μ 表面與下表面（也就是，該圓盤的二個主二上 議。在使用時’每個藥物姆裝都經過該頂二:- 依序==:，藉此該粉末狀配方會暴露於輸送裝置中而 在上述的谷器中，該藥物封 罝中。 以排出該孔洞。因此，爾力圓日盤滑動 要可以自由地相對於該圓盤而移動。為了要使該率Ζ需 可以移動’該孔洞應該不具有該熱密封聚合物， 20 200823110 疋要/又有任何的扭曲，以避免或阻止該藥物封裝離開該圓 盤。 【餐^明内溶^】 本發明的一目的是要克服上述問題中之至少一者。 依妝本發明的一第一態樣，其提供一種用於將一障蔽 薄膜益封至一聚合物圓盤之板件，其中該聚合物圓盤包含 有數個孔洞’其等每個都包含一被可滑動地連結至該圓盤 的藥物封裝’該板件包含有對應於該聚合物圓盤的孔洞之 孔洞區域以及至少一突緣，其中該孔洞區域係不具有突 1〇緣，而該突緣係與該孔洞區域距離一定間隔。 提供包含有一或更多的突緣之板件以及不具有突緣的 孔洞區域’代表在該圓盤的每個孔洞附近的區域將不會接 受來自於該板件的壓力。因此，即使在每個孔洞附近區域 的。亥F早蔽薄膜之熱密封層會熔化，其也不會被擠壓而與該 15孔洞接觸’且因而不會使得該熱密封聚合物流入孔洞内而 將該藥物封裝黏著至該孔洞。 此外’該聚合物圓盤係典型地以射出模製來形成，在 其製私期間，該聚合物材料在冷卻時通常會收縮，而會在 該頂端和底部表面留下淺淺的凹孔。使用依照本發明之該 2〇板件將可以克服將障蔽薄膜密封至含有此等的缺陷的表面 之問題。 此外，假使在圓盤的表面上具有任何的污染（舉例來說 藥物粉末），那麼該突緣就會釋放出相對較高的局部壓力， 而使得该熱岔封材料與圓盤聚合物材料流動遠離該突緣， 200823110 而且這會將污染物自密封面積下移開而達成一良好的密封 作用。 山 又進一步來說，該突緣係距離該孔洞區域一定間隔， 代表其在被使用時該板件不會扭曲該圓盤的孔洞以致於該 5 藥物封裝無法滑出該孔洞。 “障蔽薄膜”這個術語應該被解釋為任何能夠被密封至 該圓盤表面，其可以避免或限制該圓盤的内 部環境而降解。該障蔽薄膜係典型地包含一包括—熱密= 層作為外層的層合板，該熱密封層包含有一熱密 10物，其係被熱所活化並且係被用來將該障蔽薄膜黏著= 圓盤。障蔽薄膜的-具體例包含一具有紹層以及―二 =物層的層合板。“’魏料物或是聚合 來取代一此之外，其可— 可α動地連接㊉個術語係仙來界定該 該的關係。該藥物封裝係位在該孔 2 施加適當的力量*:，該藥物封褒能夠相對於該孔洞二在 或移動以使得該藥物封萝 、 而q動 的材料所界定並且係在W該孔洞。該孔洞係由該圓盤 0開口端係以障蔽薄犋來子末知具有開口，其中該相對 ί閉。因此，該攀物射获 、 將其壓過位在該孔祠_ 藉著 洞。 ’早敝相而退出該孔 在本發明的一具體例 二 件能夠在該板件的形成中使用二環形板 取夕之材科下，该配合圓盤 200823110 之至少一部分。這可以產生一比較容易加熱的板件，並且 其以使用較少的能量來維持一比周圍溫度更高之溫度。其 也可減少製造成本。 该圓盤的π亥專孔/同可以被排列成一圓形陣列，其等係 5典型地距離該圓盤的中心軸一相等的間隔。因此，該板件 的该孔洞區域可以被排列成一圓形陣列以使得該板件的孔 洞區域可以配合該圓盤的該等孔洞。 在上文各處所界定之本發明的進一步具體例中，該板 件包含至少一周圍突緣。該突緣可以是一單一圓形突緣； 1〇 -在徑向方向中具有至少二個突緣之單—螺旋狀的突緣， 也就是，該螺線包含至少二環繞該板件的螺圈並因此可以 提供相鄰的突緣部分；或者其可以包含二或更更多分離的 圓形突緣或分離的螺旋狀突緣。該等周圍突緣係位在該板 件的孔洞區域與該板件的周圍邊緣之間。 ^ X氣係典型地經由該熱密封聚合物層而進人該圓盤的 人封裝内。因此’對於一圓筒形的，盤而言，該熱密封 =合物的唯-暴露於外部環境的部分係位在該圓盤的周園 =。藉著著在該板件上提供至少-周圍突緣，可以在該 20妊沾、周圍邊緣與在該孔洞裡的藥物封裝之間被獲得，艮 巧密封作育。這可以使得經由該熱密封層之水分進八減 判瑕少。 可選擇地，該周圍突緣係被架構以在使用時在該最外 二緣與該圓盤的邊緣之間界定-間隙。其可以避免或減 μ圓盤的邊緣在該密封過程中扭曲的風險。在-些應相 9 200823110 中，圓盤的邊緣不會發生形變是很重要的，特別是在該圓 盤需要被精確地對準者。 在上文各處所界定之本發明的進一步具體例中，該板 件包含二或更多的圓形突緣、或一具有至少二個環繞該板 5 件之完整螺圈的螺旋狀突緣，以及數個橋接相鄰的周圍突 緣或突緣部分(在螺旋狀突緣的情況下）之橫向突緣。 在一圓盤密封之後，該板件的性質是會使得其具有在 該等突緣所形成的密封之間的未形成良好密封之區域。換 句話說，在該板件上對應於該等突緣之間的該等間隙的區 10 域中，可能會在障蔽薄膜和圓盤表面之間形成間隙。因此， 任何滲入這個區域的水氣將可以自由在由該等間隙（也就 是，在該圓盤的相鄰密封部分之間）所形成的溝槽各處中移 動。提供橋接在板件上之周圍突緣或突緣部分的橫向突 緣，因此可以侷限形成於該等周圍密封之間的任何溝槽之 15 連通性，並減少在這些溝槽裡面的水氣移動。 在上文各處所界定之本發明的進一步具體例中，該板 件包含至少一在該等相鄰的孔洞區域之間延伸的個徑向突 緣。該徑向突緣可以避免在該等孔洞區域之間的連通，並 因此使得水氣從一藥物封裝移動到鄰近的藥物封裝之能力 20 減到最小。 在上文各處所界定之本發明的又進一步具體例中，該 板件包含位在該孔洞區域與該板件的中央軸心之間的至少 一核心突緣。該核心突緣係類似於該周圍突緣，但是其係 位在該孔洞區域的内側而非該的孔洞區域的外側。因此， 10 200823110 該核心突緣可以是一單一圓形突緣；一在徑向方向中具有 至少二個突緣之單一螺旋狀的突緣，也就是，該螺線包含 至少二環繞該板件的螺圈；或者其可以包含二或更更多分 離的圓形突緣或分離的螺旋狀突緣。 5 該核心突緣係可以被用於密封外形為環狀之圓盤是。 如上述所討論的，一圓筒形圓盤只會將該熱密封聚合物的 一邊緣部分暴露於外部環境，然而一環狀圓盤則會將其之 二個邊緣部分都暴露出來（也就是該環狀的周圍邊緣和内 側邊緣）。為了要侷限或避免水氣經由該熱密封層的該内側 10 邊緣滲入該圓盤的該藥物封裝，一包括至少一如上述所界 定的核心突緣之板件，可以被用來在該圓盤的内側邊緣和 藥物封裝之間形成一良好的密封作用。 在上文各處所界定之本發明的又進一步具體例中，該 板件包含二或更多的圓形核心突緣或是一包括至少二個圓 15 盤的螺圈以提供相鄰的突緣部分之螺旋狀突緣，其中相鄰 的核心突緣或是突緣部分係被至少一橋接突緣來橋接。 如上述所討論的，該橋接作用或橫向突緣之目地在於 限制可以形成於由相鄰核心突緣產生之密封之間的任何溝 槽之間或沿著其等之通連作用。 20 在上文各處所界定之本發明的進一步具體例中，該板 件包含數個孔洞突緣，其等每個都會環繞或包圍該板件的 各別孔洞區域，並且係被架構以在該孔洞區域和該孔洞突 緣之間界定一間隙。 該等所使用的孔洞突緣可以在圓盤中之該等孔洞和藥 11200823110 IX. INSTRUCTIONS: [Technical Field 3 of the Invention The present invention relates to the sealing action of a container. For example, it relates to the sealing action of a container formed from a polymer disc, wherein the container 5 contains a pharmaceutical package containing a pharmaceutical formulation in the form of a powder. C Prior Art 3 The use of heat and/or pressure to bond an aluminum foil laminate sheet into a polymer container is a development that has been fully developed to seal the drug package against environmental contamination such as moisture penetration. Methods. The sealing action system 10 is fused to the polymer surface of the container by laminating a layer of heat-sealing polymer sheet laminated to the aluminum foil laminate sheet, and applying pressure to cause the heat-sealed polymer to melt with the container or The softened layer is fused and the aluminum foil of the container is attached. The quality of the sealing action is based on the extent to which the heat seal polymer is sufficiently fused to the container over the entire sealing area. - 15 Although the aluminum foil can provide a substantially sufficient moisture barrier effect, the heat seal layer of the laminate which does not have complete impermeability for the water vapor permeation provides a moisture to reach the container The pathway for inclusions (for example, a pharmaceutical product). However, when the heat seal layer is thin and the distance between the surfaces of the contents and the surface of the contents is long enough when the layer is exposed to the environment, the moisture that penetrates the heat seal layer can be reduced to one. The extent of acceptance. The seal can be formed using a heated roller or a heated planar plate. The temperature and contact time used are sufficient to dissolve the heat seal layer and the thin layer of the contact surface of the container. The applied pressure then fuses the two melted 5 200823110 levels together and causes the molten material to flow away from any point on the contact area until the entire sealing area is brought together. Straight can guarantee a good seal in the entire sealing area. However, there are some problems associated with this known method. First, the method is not suitable for use in all types of containers. Second, the thin layer of the heat-tight compound cannot cope with the final relatively large deviation or processing of the container sealing surface, and thirdly, the integrity of the seal may be on the sealing surface of the container. Or the contaminants (for example, drug particles) on the heat seal layer of this level are harmful. 10 15 Not applicable to the traditional sealing method described above. A container type is described in W〇 03/015857, wo 03/0664 chest (10) 〇 5/002654. The device includes an annular shape in which a plurality of holes are formed through the disk; the disk ' is shaped such that the holes will surround the central axis of the disk. Each hole is accommodated - encapsulated by a drug inside the hole, whereby the drug = the hole is removed from the hole. The package may contain a pharmaceutical formulation of = two relative to the disc. In order to protect the 哕, i8/#1± powder-shaped main t-tongue substance' the disc is on the surface of the complex μ and the lower surface (that is, the two main two of the disc are discussed. When each drug is passed through the top two: - in order ==:, whereby the powdered formulation is exposed to the delivery device and in the above-mentioned barn, the drug is sealed. To discharge the hole Therefore, the Erli round slide should be free to move relative to the disc. In order to make the rate unmovable, the hole should not have the heat-sealed polymer. 20 200823110 / /有有 any Distortion to avoid or prevent the drug from being packaged away from the disk. [Embodiment] It is an object of the present invention to overcome at least one of the above problems. There is provided a plate for encapsulating a barrier film to a polymer disk, wherein the polymer disk comprises a plurality of holes each of which comprises a drug slidably coupled to the disk Package 'this plate contains holes corresponding to the holes of the polymer disc a region and at least one flange, wherein the hole region does not have a flange, and the flange is spaced apart from the hole region. A plate member having one or more flanges and a flange without a flange is provided. The hole area 'represents a region near each hole of the disk that will not receive pressure from the plate. Therefore, even in the vicinity of each hole, the heat seal layer of the film is melted, It also does not be squeezed into contact with the 15 holes and thus does not cause the heat seal polymer to flow into the holes to adhere the drug package to the holes. Furthermore, the polymer disk is typically in the exit mode. Formed to form, during its manufacture, the polymeric material typically shrinks upon cooling, leaving shallow recesses in the top and bottom surfaces. The use of the 2 〇 plate member in accordance with the present invention can be overcome The problem of sealing the barrier film to a surface containing such defects. Furthermore, if there is any contamination (for example, a drug powder) on the surface of the disk, the flange will be released relatively The partial pressure causes the hot seal material and the disc polymer material to flow away from the flange, 200823110 and this will remove the contaminants from the seal area to achieve a good sealing effect. Further, the mountain The flange is spaced from the area of the hole to indicate that the plate does not distort the hole of the disk when it is in use so that the 5 drug package cannot slide out of the hole. The term "barrier film" should be interpreted as any Can be sealed to the surface of the disc, which can avoid or limit the degradation of the internal environment of the disc. The barrier film typically comprises a laminate comprising a heat-tight layer as an outer layer, the heat seal layer comprising a heat A dense substance, which is activated by heat and is used to adhere the barrier film to the disk. The specific example of the barrier film comprises a laminate having a layer and a layer. "'Where the material is aggregated or replaced by a single one, it can be - can be linked to ten terms to define the relationship. The drug encapsulation system applies the appropriate force in the hole 2*: The drug seal can be positioned or moved relative to the hole to define the material of the drug, and the material is bound to the hole. The hole is blocked by the open end of the disk 0. At the end of the journey, there is an opening, wherein the relatively closed. Therefore, the climbing object is shot and pressed over the hole _ by the hole. 'Early 敝 phase and exit the hole in a specific example of the present invention Two pieces can be used in the formation of the plate, using at least a portion of the disc 200823110. This can produce a relatively easy to heat plate and it is maintained with less energy. a temperature higher than the ambient temperature. It can also reduce the manufacturing cost. The πHai/holes of the disk can be arranged in a circular array, which is typically equal to the central axis of the disk. Interval. Therefore, the hole area of the plate The arrays can be arranged in a circular array such that the aperture regions of the panel can engage the apertures of the disk. In a further embodiment of the invention as defined above, the panel comprises at least one peripheral flange. The flange may be a single circular flange; 1〇- a single-spiral flange having at least two flanges in the radial direction, that is, the spiral comprises at least two snails surrounding the plate The ring and thus may provide adjacent flange portions; or it may comprise two or more separate circular flanges or separate helical flanges. The peripheral flanges are tied in the hole region of the plate and Between the peripheral edges of the panel. ^X gas system typically enters the human package of the disc via the heat-sealable polymer layer. Thus, for a cylindrical, disc, the heat seal = The only part of the object that is exposed to the external environment is in the circumference of the disc. By providing at least a peripheral flange on the panel, the 20 points can be placed in the surrounding edge and in the hole. The drug package is obtained between the seals and the well-being. The moisture passing through the heat seal layer can be reduced. Alternatively, the peripheral flange is configured to define a gap between the outermost edge and the edge of the disk when in use. It is possible to avoid or reduce the risk of the edge of the disc being distorted during the sealing process. It is important that the edge of the disc does not deform in the phase 9200823110, especially if the disc needs to be accurately In a further embodiment of the invention as defined above, the panel comprises two or more circular flanges, or a spiral having at least two complete turns around the plate 5 a flange, and a plurality of lateral flanges bridging adjacent peripheral flanges or flange portions (in the case of a helical flange). After a disc seal, the nature of the panel is such that it has A region of the seal formed by the flanges that does not form a good seal. In other words, a gap may be formed between the barrier film and the surface of the disk in the region 10 of the plate corresponding to the gaps between the flanges. Therefore, any moisture that seeps into this area will be free to move throughout the grooves formed by the gaps (i.e., between adjacent sealing portions of the disk). Providing a lateral flange that bridges the peripheral flange or flange portion of the panel, thereby limiting the 15 connectivity of any grooves formed between the surrounding seals and reducing moisture movement within the grooves . In a further embodiment of the invention as defined above, the panel includes at least one radial flange extending between the adjacent regions of the aperture. The radial flanges avoid communication between the regions of the holes and thus minimize the ability of moisture to move from a drug package to an adjacent drug package. In still further embodiments of the invention as defined above, the panel comprises at least one core flange positioned between the region of the aperture and the central axis of the panel. The core flange is similar to the peripheral flange, but is anchored to the inside of the hole region rather than to the outside of the hole region. Thus, 10 200823110 the core flange may be a single circular flange; a single helical flange having at least two flanges in the radial direction, that is, the spiral comprises at least two surrounding the plate a coil; or it may comprise two or more separate circular flanges or separate helical flanges. 5 The core flange can be used to seal a circular disk. As discussed above, a cylindrical disk will only expose an edge portion of the heat-sealable polymer to the external environment, whereas an annular disk will expose both of its edge portions (i.e., Annular peripheral edge and inner edge). In order to limit or prevent moisture from penetrating into the drug package through the inner 10 edge of the heat seal layer, a plate member comprising at least one core flange as defined above may be used in the disk A good sealing effect is formed between the inside edge and the drug package. In still further embodiments of the invention as defined above, the panel comprises two or more circular core flanges or a coil comprising at least two round 15 discs to provide adjacent flanges A portion of the helical flange wherein adjacent core flanges or flange portions are bridged by at least one bridging flange. As discussed above, the bridging action or lateral flanges are intended to limit the effects of any of the grooves between the seals created by adjacent core flanges or the passages therethrough. 20 In a further embodiment of the invention as defined above, the panel comprises a plurality of aperture flanges, each of which encircles or encloses a respective aperture region of the panel and is configured to A gap is defined between the hole region and the hole flange. The hole flanges used in the discs can be such holes and medicines in the disc.
Ullo 圍提供—良好的密封作用，其可以進—步將滲入 二物封巢之水氣制最少。t壓力藉_板件而施加至該 員皿的日寸候，⑦孔洞突緣和孔洞區域之間的間隙需要可以 在密封過程期間避免在該圓盤中的孔洞的變形。如果沒有 該間隙，-些圓盤聚合物材料可能會因為該孔洞突緣而流 入孔洞内，因而阻止或抵抗藥物封裝相對於盤而可滑 動地移出該孔洞。因此，該間隙可以在該板件被擠壓而與 該圓盤接觸的時候，藉由該孔洞突緣來避免在該圓盤裡的 孔洞變形。 ίο 在上文各處所界定之本發明的進一步具體例中’該板 件的突緣包含不具有銳利邊緣的—接觸區域。在將障蔽薄 Μ饮封至《盤的時候，該板件的突緣會產生一會扭曲障 蔽薄膜之相對較高的局部壓力。在該接觸區域或該突緣部 Τ上的不具有銳利邊緣，可以減少在密封過程期間該障蔽 !5 薄膜破裂的可能。 #該突緣的“接觸區域，，應該被解釋為在密封過程期間該 突緣被壓迫而與該障蔽薄膜接觸的部份。 該突緣的接觸區域係典型地為該i緣的頂點，而-不 具有銳利邊緣之突緣的-具體例就是提供該突緣頂點一個 固形輪廉（也就是其會具有一實質上―致的半外 如上所述，以射出模製所形成的圓盤在冷卻期間會受 到表面形變的影響。此一形變可能會在圓盤的表面上造成 凹洞和突出點。當在該圓盤的表面中之最大高度變化(也就 疋，该突出點尖端與該凹洞的下凹處之間的差值)被界定為 12 200823110 h，而該突緣可以具有—高度H(也就是該突緣從該板件的表 面延伸的最大距離）時，該臟數值的範圍係介於㈣。本 發明的-具體例可以包含H/h值介於2 5至3 5的範圍中之突 緣。換句話說，該突緣的高度可以被選定為該圓盤的最大 5高度變化之2至8倍(任擇地為2.5至3.5倍）。 H/h值介於2至8之間可以確保儘管在該圓盤表面上有 缺限，其仍能達成一良好的密封作用。 在上文各處所界定之本發明的進—步具體例中，該板 件包含有加熱源，其能夠將該板件加熱至_高於溫度 〇之溫度。該板件可以進一步包含—用於將該板件維持在一 預定的較高溫度下的控制機構。 本發明的一第二態樣提供—種將-障蔽薄膜密封至一 聚合物圓盤的方法，其中該聚合物圓盤包含數個孔洞，i 等每個都包含-可滑動連接至地該圓盤的藥 5 法包含有： 乃 \ 20 h將一包括—膠黏層的障蔽薄膜施加至該圓盤；並且 η·經過上狀本發日㈣第1樣的板件將熱能盘壓力 施加至該障蔽薄膜的區域，其中所施加的熱能和壓 力係足以將該障蔽薄膜密封至該圓盤。 堡力可以被施加一定的時間’該時間係足以將 該障蔽薄膜密封至該圓盤，而不會扭曲該圓盤或是將該華 物封裝的内部加熱，因為該藥物封裝的内含物可能是一 度敏感物質。因此，較佳地其係以可以達成-良好密封： 用的最短時間來施加該溫度和壓力。這個時間可以是例如 13 200823110 0.1至3.0秒，更明確地為0.3到1·〇秒。 在上文各處所界定之本發明的進一步具體例中，藉由 該板件而對該圓盤所施加的壓力係為丨·20巴，更明確地為 2-10 巴。 5 在上文各處所界定之本發明的又進一步具體例中，在 依照界定的發明任何地方的一個仍然比較進一步的具體例 中，以上，該板件被加熱到90至200°C的溫度。該板件的溫 度可以被選定為125至150°C。大多數的熱密封聚合物都具 有一介於90和200°C之間的熔點。因此，一低於90°C的板件 1〇溫度可能會太低而無法熔化該熱密封聚合物層，而超過 200 C則將會冒著損害該圓盤或其之内含物的風險，並且其 無論如何都會在沒有任何優點下增加作業成本。然而，熱 密封聚合物的選擇可能會致使其使用較低的溫度，或者可 能需要使用較高的溫度。 15 除非有另外說明，上述之具體例並非是互相排斥。因Ullo provides a good seal that allows for the least amount of water infiltration into the two enclosures. The pressure between the 7-hole flange and the hole area needs to be able to avoid deformation of the hole in the disk during the sealing process. Without this gap, some of the disc polymeric material may flow into the aperture due to the hole flange, thereby preventing or resisting the slidable removal of the drug package relative to the disk. Therefore, the gap can prevent the deformation of the hole in the disk by the hole flange when the plate member is pressed into contact with the disk. Ίο In a further embodiment of the invention as defined above, the flange of the panel comprises a contact area having no sharp edges. When the barrier is sipped and sealed to the disc, the flange of the panel creates a relatively high partial pressure that would distort the barrier film. The absence of a sharp edge on the contact area or the flange portion can reduce the likelihood of the film being broken during the sealing process. The "contact area" of the flange should be interpreted as the portion of the flange that is pressed into contact with the barrier film during the sealing process. The contact area of the flange is typically the apex of the i-edge, and - a flange that does not have a sharp edge - a specific example is to provide a solid wheel of the flange apex (that is, it will have a substantially semi-outer surface as described above, to form a disc formed by injection molding During cooling, it is affected by surface deformation. This deformation may cause pits and protruding points on the surface of the disc. When the maximum height changes in the surface of the disc (ie, the tip of the protruding point and the The difference between the depressions of the cavity is defined as 12 200823110 h, and the flange may have a height H (that is, the maximum distance the flange extends from the surface of the panel), the dirty value The range of the system is between (4). The specific example of the invention may comprise a flange having a H/h value in the range of 25 to 35. In other words, the height of the flange may be selected as the disk. The maximum 5 height changes are 2 to 8 times (optionally 2.5 to 3.5 times). An H/h value between 2 and 8 ensures that a good sealing effect can be achieved despite the lack of a limit on the surface of the disc. In the specific example of the invention as defined above The plate member includes a heating source capable of heating the plate member to a temperature above 〇. The plate member may further comprise a control mechanism for maintaining the plate member at a predetermined higher temperature A second aspect of the present invention provides a method of sealing a barrier film to a polymer disk, wherein the polymer disk comprises a plurality of holes, i, etc. each comprising - slidably coupled to the ground The medicine 5 method of the disk comprises: applying a barrier film comprising an adhesive layer to the disk; and η· applying the heat plate pressure through the first plate of the upper surface (4) To the area of the barrier film, wherein the applied thermal energy and pressure are sufficient to seal the barrier film to the disk. The fortification force can be applied for a period of time sufficient to seal the barrier film to the disk. Will not distort the disc or package the Chinese Internal heating, as the contents of the drug package may be once sensitive. Therefore, it is preferred to apply the temperature and pressure in a short time that can be achieved - good sealing. This time can be, for example, 13 200823110 0.1 to 3.0 seconds, more specifically 0.3 to 1·〇 seconds. In a further embodiment of the invention as defined above, the pressure applied to the disk by the plate is 丨·20 Bar, more specifically 2-10 bar. 5 In still further specific examples of the invention as defined above, in a still further specific example anywhere in accordance with the defined invention, above, the panel It is heated to a temperature of 90 to 200 C. The temperature of the plate can be selected to be 125 to 150 C. Most heat-sealing polymers have a melting point between 90 and 200 °C. Therefore, a sheet of temperature below 90 ° C may be too low to melt the heat-sealable polymer layer, and more than 200 C will risk damaging the disc or its contents. And in any case, it will increase the operating cost without any advantage. However, the choice of heat-sealable polymer may result in lower temperatures or may require higher temperatures. 15 Unless otherwise stated, the above specific examples are not mutually exclusive. because
S 此，在本發明的上述具體例中之任何的二或更多種之該等 個別特徵都可以一起與本發明第一個或第二態樣結合。因 此，上述所使用的術語“具體例，，應該被解釋為“如任何前述 〃體例或怒樣所界定之本發明的一具體例”。 2〇圖式簡單說明 隨附說明的方式參照該等 第1圖 弟2圖 疋依照本發明之板件頂視平面圖； 疋在第1圖中所顯示的板件之-區域的放大圖； 14 200823110 並且 第3圖係為在第i圖中所顯示之板件的_部份之的剖視 圖〇 【貧掩•方式】 5 以圖顯示一具有一周圍邊緣作一個内側邊緣6之環 咸件2。該板件包含有數個繞著該板件的轴而設置成一圓 形陣列之孔洞區域8。該等孔洞區域8不具有任何突緣並且 係被排列以對應於欲被密封之圓盤孔洞。 在該等孔洞區域8和該周圍邊緣4之間設置有四個共心 1〇的周圍突緣10。在第3圖顯示該等周圍突緣的剖面並且其等 每個都具有一係為0.5公釐之直徑及係為〇·3公釐之高度 b，其中該係被界定為從該突緣向外延伸的最大距離。如在 第3圖中所示，該等突緣10，12，14，16，18,2〇的頂端係形成為 圓形並且具有一實質一致的半徑。 15 如第1和2圖中所示，相鄰的周圍突緣10係被一些徑向 大緣12所連接，其等係被架構以將在由相鄰的突緣1〇所界 定的溝槽加以環繞地間隔。該周圍突緣10之鄰近於徑向突 緣12的部份在寬度上將從〇·5公釐減少至〇.4公釐。這一點可 以在第2圖中被看得更清楚，其中一弧形凹槽22係在該等周 20圍突緣10被徑向突緣12所連接處，形成於每個周圍突緣10 中。 在該等孔洞區域8和該内侧邊緣6之間設置有四個共心 的核心突緣14該等核心突緣14係以類似於該等周圍突緣1〇 的方式來架構’其中相鄰的核心突緣14係在由相鄰核心突 15 200823110 緣14所界定的溝槽内的間隔之間以橋接突緣18來橋接。 在每個孔洞區域8之間係為一徑向突緣16，其係自最外 側的核心突緣14延伸至該最内侧的周圍突緣1〇，並且分隔 在孔洞區域8之間的地區。 5 環繞每個孔洞區域8的是一孔洞突緣20。該孔洞突緣2〇 係距離該孔洞區域8—定距離，該距離在作業時可以避免或 或使得該圓盤的該等孔洞在在密封過程期間的扭曲變形減 到最少。 該板件包含有在此技藝中所㈣之加熱源(未顯示），且 10 其因此將不會在此被更詳細地描述。 在使用時，該板件係被用來密封一環形高密度聚乙稀 (HDPE)圓盤。該HDPE圓盤包含數個環繞著該圓盤的中轴 而排列成-圓形陣列的孔洞，在每個孔洞都容納了一被恰 當適切地收容於其中之藥物封裝。該藥物封裝每個都包: 15有-係為粉末形式之藥學配方。該圓盤係被射出模製而形 成，亚且其具有G.〇5至G.15公釐的表面高度變化。其可以提 供至少為2之H/h值(該圓盤的突緣高度/表面高度變化）。That is, the individual features of any two or more of any of the above specific examples of the invention may be combined together with the first or second aspect of the invention. Therefore, the term "specific example" as used above shall be interpreted as "a specific example of the invention as defined in any of the foregoing corpusses or writhings". 2 〇 简单 简单 简单 简单 简单 简单 简单 随 随 随 随 随 随 随BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a top plan view of a panel according to the present invention; 放大 an enlarged view of a panel-area shown in Fig. 1; 14 200823110 and Fig. 3 is shown in Fig. A cross-sectional view of the _ portion of the panel 〇 [poor masking mode] 5 shows a ring-shaped member 2 having a peripheral edge as an inner edge 6. The panel comprises a plurality of axes around the panel The aperture regions 8 are arranged in a circular array. The aperture regions 8 do not have any flanges and are arranged to correspond to the disc holes to be sealed. Between the aperture regions 8 and the peripheral edge 4 There are four concentric peripheral flanges 10. The cross-sections of the surrounding flanges are shown in Figure 3 and each has a diameter of 0.5 mm and a height of 〇·3 mm. b, wherein the line is defined as the largest outward extension from the flange As shown in Fig. 3, the apexes of the flanges 10, 12, 14, 16, 18, 2 are formed in a circular shape and have a substantially uniform radius. 15 As shown in Figures 1 and 2 As shown, adjacent peripheral flanges 10 are joined by a plurality of radial major edges 12 that are configured to circumferentially space the grooves defined by adjacent flanges 1〇. The portion of the edge 10 adjacent to the radial flange 12 will be reduced in width from 〇·5 mm to 〇4 mm. This can be seen more clearly in Figure 2, where a curved concave A groove 22 is formed in each of the peripheral flanges 10 at a circumference where the circumferential flange 10 is joined by the radial flange 12. Four common spaces are provided between the hole regions 8 and the inner edge 6 The core flange 14 of the heart is constructed in a manner similar to the surrounding flanges 1 'where adjacent core flanges 14 are bounded by the edge 14 of the adjacent core protrusion 15 200823110 The gaps in the trench are bridged by bridging flanges 18. Between each of the bore regions 8 is a radial flange 16 extending from the outermost core flange 14. To the innermost peripheral flange 1〇, and separated in the region between the hole regions 8. 5 Surrounding each of the hole regions 8 is a hole flange 20. The hole flange 2 is spaced from the hole region 8 - a distance that avoids or causes the holes of the disc to minimize distortion during the sealing process during operation. The panel comprises a heating source (not shown) in the art (four) And 10 will therefore not be described in more detail herein. In use, the panel is used to seal a circular high density polyethylene (HDPE) disc. The HDPE disc contains several surrounds. The central axis of the disk is arranged in a circular array of holes, each of which houses a drug package that is properly accommodated therein. The drug package is each packaged: 15 has a pharmaceutical formulation in powder form. The disc is formed by injection molding, and has a surface height variation of G. 〇 5 to G. 15 mm. It can provide an H/h value of at least 2 (the flange height/surface height variation of the disc).
-包含有-熱密封聚合物層之|gf薄膜層合板係被設 置於該圓盤上，並且參照第M圖所描述之上述板件係被壓 20向該圓盤。該板件係被維持在一足以溶化該層合板的熱密 封聚合物以及該圓盤_密封表蚊腳£的溫度下。在該 等突緣與該铭質薄膜接觸時，來自該板件的熱量係被立刻 傳輸通過在該突緣下方之該銘層而到達該熱密封層以及該 圓盤表面的HDPE。在該突緣下方之該熱密封層與該HDpE 16 200823110 力將會迫使該突緣進 側邊上移置該經熔化 聚合物都會熔化，而來自該板件的髮 入5亥圓盤表面，因而在該突緣的你〜 的 HDPE。 該板件係壓向該®盤直賴被移置师刪已經填滿 在相鄰突緣之間的溝槽。換句話說，就是直到在二相鄰突 緣所界定的溝槽之殘餘容積為零。㈣，由於該被移置的 材料將沒_法流動到其他地，叫件的突緣可以避免呈 進一步穿透進人該圓盤内。在該被件的作《統中之-壓 力感應器會仙到此-最大的穿遷作驗果，並且中止該 10 密封過程。 或者，該板件的作業系統可以包含一機械播止，其可 以在該板件的突緣已㈣❹卜預定的深度時中止該密封 過程。 忒突緣的半徑以及該密封薄膜的選定，因而可以使得 15 ,亥銘層不會在⑨封過程期間破裂。所使用的突緣頂點之最 J半彳二係依據包含在薄膜層合板中之鋁的硬度而定。一包 括有、差退火|呂層的層合板將可以允許其被更加穿透進入該 圓盤表面及/或允許該突緣使用較小的曲率半徑的。其也更 可以谷心在《突緣上之任何的銳利邊緣。 0 4大緣距離該板件的孔洞區域之間隔係足以使得在該 圓戚中的孔洞邊緣在密封期間發生產生扭曲形變。該形變 可以被侷限⑽H、於該突緣的高度。 /板件與圓盤接觸的時間係被選定，以使得將該具黏 1±的、工炼W材料移置之力量係不足以使得該薄膜破裂，同 17 200823110 時不會長到使得熱量穿過該圓盤而到達包含有活性藥物產 品之藥物封裝。 典型地’邊接觸時間係為〇·3至丨.〇秒，而該板件所施加 的壓力為2至10巴且該板件的溫度為13〇s15〇〇c。 5 測試實驗顯示本發明可以提供一種具有水氣障蔽效果 的岔封作用，該密封作用係相當於具有在該表面是平坦的 並使用一傳統的扁平板件來在整個的密封面積上形成一密 封之容器所能達成的效果。 除此之外’測試實驗顯示在密封過程期間當粉末出現 10 在圓盤表面上時，並不會降低密封品質。 【圖式簡單說明3 第1圖是依照本發明之板件頂視平面圖； 第2圖是在第1圖中所顯示的板件之一區域的放大圖； 並且 15 第3圖係為在第1圖中所顯示之板件的一部份之的剖視 圖。 【主要元件符號説明】 2…環形板件 16···經向突緣 4···周圍邊緣 18···橋接突緣 6···内側邊緣 2〇···孔洞突緣 8···?1洞區域 22···弧形凹槽 10…周圍突緣 a…突緣直捏 12…徑向突緣 b…突緣高度 14…核心突緣 18- a gf film laminate comprising a heat-sealable polymer layer is placed on the disk, and the above-described plate member described with reference to Figure M is pressed 20 toward the disk. The panel is maintained at a temperature sufficient to dissolve the heat seal polymer of the laminate and the disc-sealed mosquito foot. When the flanges are in contact with the texture film, heat from the panel is immediately transmitted through the layer below the flange to the HDPE and the HDPE of the disc surface. The heat seal layer under the flange and the force of the HDpE 16 200823110 will force the flange to be displaced on the side and the molten polymer will melt, and the surface of the plate from the 5 liter disk is Thus in the flange you ~ HDPE. The panel is pressed against the ® disc to remove the groove that has been filled between adjacent flanges. In other words, the residual volume until the groove defined by the two adjacent flanges is zero. (d), since the displaced material will not flow to other places, the flange of the caller can be prevented from further penetrating into the disc. In the work of the piece, the pressure sensor will be sent to this - the largest pass-through test, and the 10 sealing process is aborted. Alternatively, the operating system of the panel may include a mechanical broadcast that may terminate the sealing process when the flange of the panel has been (4) predetermined depth. The radius of the ridge flange and the selection of the sealing film can thus cause the haiming layer to not break during the nine sealing process. The most semi-final of the flange apex used is determined by the hardness of the aluminum contained in the film laminate. A laminate comprising a differential annealing layer will allow it to be more penetrated into the surface of the disk and/or allow the flange to use a smaller radius of curvature. It can also be more of a sharp edge on the edge of the flange. The gap of the major edge of the panel is sufficient to cause a distortion of the edge of the hole in the dome during sealing. This deformation can be limited to (10) H at the height of the flange. / The time the plate is in contact with the disc is selected such that the force that displaces the viscous material is not sufficient to cause the film to rupture, and does not grow as long as 17 200823110 to allow heat to pass through The disc reaches the drug package containing the active drug product. Typically, the edge contact time is 〇·3 to 丨.〇 seconds, and the plate is applied with a pressure of 2 to 10 bar and the temperature of the plate is 13 〇s15 〇〇c. 5 Test experiments show that the present invention can provide a sealant having a water-gas barrier effect, which is equivalent to having a flat surface on the surface and using a conventional flat plate member to form a seal over the entire seal area. The effect that the container can achieve. In addition to this, the test results showed that when the powder appeared on the surface of the disc during the sealing process, the quality of the seal was not lowered. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a top plan view of a panel according to the present invention; FIG. 2 is an enlarged view of a region of the panel shown in FIG. 1; and FIG. 3 is a Figure 1 is a cross-sectional view of a portion of the panel shown. [Description of main component symbols] 2... annular plate member 16··· warp flange 4···surrounding edge 18···bridge flange 6···inside edge 2〇···hole flange 8··· ? 1 hole area 22 · · arc groove 10 ... around the flange a ... flange straight pinch 12 ... radial flange b ... flange height 14 ... core flange 18