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`W001lfl36?6
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`PCTI'G 3001’0261 6
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`This invention relates to a delivery capsule, that is, a capsule designed to retain and protect
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`its contents until an intended site of delivery or conditions of delivery are encountered, at
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`which point the capsule contents are released.
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`Backgmdtethelnxentinn
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`Delivery capsules are well known and find particular application in the form of ingestible
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`gelatin capsules
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`for
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`the delivery of accurately metered doses of pharmaceutical
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`preparations and dietary supplements. Liquid preparations are typically encapsulated in
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`soft gelatin capsules and particulate or powdered preparations are typically encapsulated in
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`two part hard gelatin capsules. The capsules are designed to release their contents after
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`ingestion, typically by solution of the capsule wall, and by use of suitable capsule material
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`can thus provide a means of administering a dose of a preparation at a desired appropriate
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`site in the body. The finished capsules offer protection to the contents yet solubility within
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`the body.
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`Other uses of delivery capsules include delivery of cosmetic ingredients, eg fragranced
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`bath oils encapsulated in soft gelatin capsules for release into bath water, paint balls in the
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`form of paint-containing capsules that rupture on impact etc.
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`There are limitations on current capsules and encapsulation techniques. For example,
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`because of differences in powder and liquid handling,
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`the processing means for the
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`encapsulation of powders and liquids within a gelatin capsule are quite distinct and
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`incompatible.
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`This situation renders impossible the provision of a gelatin capsule
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`containing both powder and liquid that are kept separate.
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`W0 le03676
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`PCTIGBOOI'OZfilé
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`The present invention seeks to address certain shortcomings and limitations of current
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`2
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`capsules and encapsulation techniques.
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`Snmmanactthalnnentitm
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`In one aspect the invention provides a delivery capsule having at
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`least
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`two separate
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`chambers.
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`The chambers of the capsule are completely discrete and separated from each other so that
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`no communication between the chambers is possible. This means that the contents of the
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`different chambers are kept separate from each other within the capsule until delivery.
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`In most cases, different chambers of the capsule will contain different materials, possibly
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`in different physical forms, eg liquid, solid (cg tablet, particulate, powdered), slurry etc,
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`in a way that has not hitherto been possible. although it is also possible for the different
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`chambers to contain separate doses of the same material.
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`The capsule is preferably internally divided by a dividing wall or septum, conveniently in
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`the form of a median wall symmetrically arranged to form two chambers of similar size
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`and shape.
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`One or more chambers of the capsule may be further divided if required, eg by inclusion
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`in a chamber of a smaller delivery capsule, constituting a further separate chamber.
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`The invention thus provides a compartmented capsule in a way that has not been done
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`hitherto.
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`Indeed,
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`it is believed that this is not possible with known techniques for gelatin
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`encapsulation.
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`Instead of using gelatin for encapsulation,
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`the present invention preferably uses a heat-
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`sealable material
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`that
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`is capable of deforming plastically on heating (a thermoplastic
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`material) andfor that
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`is capable of deforming plastically when partially solvated by
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`W0 01f03676
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`PCTIGBBOIIJZISI 6
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`3
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`application of an appropriate solvent. Suitable materials include hydroxy propyl methyl
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`cellulose
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`(HPMC),
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`pectin,
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`polyethylene
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`oxide,
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`polyvinyl
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`alcohol,
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`alginate,
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`polycaprolaetone, gelatinised starch-based materials etc. The material may be coated, eg
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`with gum arabic, pectin, alginate eg sodium alginate etc to modify properties.
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`For
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`example, gum arabic, pectin and alginate all have a slight retarding effect on HPMC
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`solubility, the extent of the effect varying according to coating thickness. Further, both
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`pectin and alginate can be cross-linked, eg with calcium, this has the effect of making the
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`material pH sensitive such that it will not dissolve in the mouth but will dissolve in the
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`stomach where pH is lower. Multi-layer materials may also be used. Examples of
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`suitable capsule materials and coatings are given in W0 978553? and WO 00127367. The
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`capsule materials also have the advantage compared with gelatin of being non-animal
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`derived, and so having no possibility of transmitting animal-related diseases such as bovine
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`spongiform encepehalopathy (BSE). Such materials are commercially available, eg in the
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`form of ribbon-like films or can be readily manufactured, eg by extrusion from solution.
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`One currently favoured material is the thermOplastic material HPMC. in expanded or non-
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`expanded form, with or without coatings. HPMC is suitable for ingestion by humans and
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`so can be used for ingestible capsules as well as other uses, eg culinary, cosmetic etc.
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`A compartmented capsule in accordance with the invention can be used simply to keep
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`separate in the respective chambers two materials prior to delivery.
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`This can be of
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`advantage,
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`for example, when delivering to the same site two materials which react
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`together on admixture: by use of a compartmented capsule in accordance with the
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`invention the two materials can be kept separate until the septum wall
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`is dissolved on
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`delivery. bringing the materials together. This approach is also useful, say, for delivery of
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`two separate pharmaceutical preparations.
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`For instance,
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`this approach is relevant
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`to
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`delivery of certain mum-component cold remedies which are currently unable to get FDA
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`approval due to concerns of possible chemical reactions prior to ingestion: by using a
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`capsule in accordance with the invention to keep the components separate within the
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`capsule prior to delivery such difficulties can be overcome. As a further example, there is
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`a drug called Acctuane which is an effective treatment for acne but which can also cause
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`birth defects.
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`In order to ensure that this does not occur birth control drugs should be
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`WO 01103676
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`PCT/GB00!02616
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`4
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`taken simultaneously with Acctuane by fertile female users. For safety reasons it would
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`thus be far preferable if the birth control drug and the acne remedy were taken together,
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`but kept separate until after
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`ingestion.
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`This can be readily achieved by use of a
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`compartmented capsule in accordance with the invention.
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`Furthermore, by using different materials (either in terms of thickness andror composition
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`andfor coatings) defining the different chambers of the capsule, it is possible to arrange for
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`release of the contents of the different chambers under different conditions, eg at different
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`specific sites within the body. The contents of different compartments can thus be targeted
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`to different specific areas within the body.
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`For instance, use of a thicker material defining one compartment may result in slightly
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`delayed release of material compared with that from a compartment defined by a thinner
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`layer of similar material.
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`Another example is the use of a pH sensitive coating on the material defining one chamber
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`so that chamber contents are released at different delivery sites dependent upon pH. Use
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`of enteric coatings such as cellulose acetate phthalate can also be used to target release, eg
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`to within the stomach. Coatings such as ethyl cellulose can be used to retard solubility
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`times. A further example is use of expanded HPMC defining one compartment and non-
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`expanded HPMC defining another compartment. Expanded HPMC film releases rapidly in
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`the month while standard, non-eXpanded film has sufficient resistance to dissolution to
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`release only after it has been swallowed, providing that it is not kept in the mouth too
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`long.
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`It is also possible to coat a finished capsule after formation with materials such as sodium
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`alginate to improve robustness or alter solubility.
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`The capsule materials may include optional colourings, eg in the form of known food dyes
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`such as FD and C yellow number 5, optional flavourings, textures etc.
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`W0 01!03676
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`PCTi’GBflfli'026lfi
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`5
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`The capsules may have a range of different sizes and shapes as appropriate dependent on
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`intended usage. Capsules are typically generally spherical, ovoid, cylindrical etc in shape.
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`preferably incorporating a median septum as described above.
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`Typical maximum
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`dimensions of the capsule are in the range 3m to 20mm, but other sizes are possible.
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`The capsules are conveniently made by a vacuum or pressure forming technique, that may
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`be loosely based on the technique described in W0 9785537 but with very substantial
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`modification.
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`In a further aspect,
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`the invention thus provides a method of encapsulation, comprising
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`supplying two films of material capable of deforming plastically on heating andfor when
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`partially soivated; heating the films andior applying solvent; forming the films into suitably
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`shaped capsule portions; supplying respective substances to be encapsulated to capsule
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`portions of each film; supplying a film of a dividing septum material to at least one of the
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`filied capsule portions; sealing the capsule portions and septum material together to form a
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`capsule having at least two separate chambers.
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`The films are preferably formed into capsule portions by appiication of elevated pressure
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`or vacuum (or reduced pressure).
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`It is preferred to use two layers of film for producing the septum, with one film applied to
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`each respective capsule portion, as handling including optional coating is easier.
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`Adhesive material is preferably applied to the various fih'n materials to help secure the
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`capsule portions and septum together. Capsule sealing is preferably accomplished by heat
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`scaling,
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`to fuse the films of material together, although other sealing methods may be
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`used.
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`Pre-formed films of material may be used. Alternatively, the films may be formed during
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`the encapsulating process, eg by being cast from solution.
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`WO 01103676
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`PCTIGBOOIGZISI 6
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`6
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`In a further aspect the invention provides encapsulation apparatus, comprising means for
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`supplying two films of material to an encapsulation unit; means for plastically deforming
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`each film to form suitably shaped capsule portions; means for supplying respective
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`substances to be encapsulated to the respective capsule portions of each film; means for
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`supplying a film of dividing septum material to at least one of the filled capsule portions;
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`and means for sealing together the capsule portions and septum material to produce a
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`capsule having at least two separate chambers.
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`The apparatus typically also comprises reservoirs of the substances to be encapsulated,
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`with associated supply arrangements adapted to supply a metered doses of the substance to
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`the capsule portions at predetermined time intervals.
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`The arrangement may employ
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`syringe pumps or the like.
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`The apparatus conveniently includes heater means for heating the capsule film material to
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`enable thermoplastic deformation.
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`The means for deforming the films conveniently comprises a pair of similar vacuum belts.
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`The invention is applicable to encapsulation of a wide range of pharmaceutical, culinary,
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`cosmetic etc ingredients, enabling delivery to different sites of different materials or
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`delivery to the same site of materials that are desirably kept separate prior to delivery.
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`Capsules described in this specification provide a delivery means with either at least two
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`distinct liquid or solid, eg powder fills, or a combination of liquid and solids, eg powder.
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`The materials can also be selected so as to exclude gelatin. The combination of materials
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`used for the capsule wall and capsule dividing septum can be chosen to release either or
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`both parts of the contents of capsule at specific sites within the body. These components
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`can then address two different specific areas or act synergistically when mixed on release
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`at the same site.
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`In the latter example the capsule is serving to prevent the mixing of the
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`two components prior to them reaching the correct site within the body as well as
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`providing an accurate dose and blend of components for maximum efficacy.
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`W0 01.103676
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`PCTIGBIJIJIO2616
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`The prCSent invention enables the encapsulation of both powders and liquids within discrete
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`chambers in an ingestible capsule. Using pre-forrned rolls of film such as hydroxy propyl
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`methyl cellulose capsules are formed with an outer shell and a dividing septum.
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`In such a
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`capsule two different materials which would react if brought together in a single chamber
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`can be kept apart until the septum wall is dissolved.
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`By the application of surface coatings to the forming rolls and the dividing layer prior or
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`post capsule formation, or the use of different materials for the forming rolls, capsules can
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`be formed which release their contents under different environmental conditions. An
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`example of this is the application to pH sensitive coatings on the outer surface of the
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`capsule wall and septum which causes the two distinct chambers to release their contents at
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`different delivery sites dependent upon the pH of the surrounds.
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`The capsules are produced on dedicated machinery employing the use of vacuum forming
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`and heat sealing, and can be filled with liquids or powders.
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`The invention will be further described, by way of illustration, with reference to the
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`accompanying drawings in which:
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`Figure 1
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`is a schematic sectional view of a delivery capsule in accordance with the
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`invention; and
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`Figure 2 is a schematic representation of one embodiment of apparatus in accordance with
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`the invention for producing a delivery capsule embodying the invention.
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`£111.. Ell
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`.
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`Referring to the drawings, Figure 1
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`illustrates schematically a generally ovoid delivery
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`capsule 10 comprising at outer shell or wall in the form of two similar half shells 12 and
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`14 each of generally semi-ovoid form, and a median dividing wall of septum 16 that
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`W0 011'03676
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`PCTlGBODIflZfilfi
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`8
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`divides the capsule into two similar chambers or compartments 18 and 20 that are
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`completely separate from each other. with no communication between the chambers 18 and
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`20 being possible.
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`Each chamber 18 and 20 contains a metered amount of a different material (not shown), eg
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`with a powdered or particulate material in chamber 18 and a liquid material in chamber
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`20, or visa versa, or with different liquid materials in each of the two chambers or with
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`different powdered or particulate materials in each of the two chambers.
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`The half shells 12 and 14 of the septum 16 may be made of similar or different materials,
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`depending on the desired properties and intended use of the capsule.
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`For example, where the function of the compartments is simply to keep two materials
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`separate from each other until release at the same site of delivery, thus can be achieved by
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`all of the capsule walls, half shells 12 and 14 and septum 16, being of the same material,
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`eg HPMC (possibly coated as discussed above).
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`However, where the capsule is designed to delivery the contents of chamber 18 and
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`chamber 20 at different sites or under different conditions, eg at different sites in the body
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`after ingestion, it is appropriate for the capsule walls to be of different material, eg with
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`half shell 12 of a first material and half shell 14 and septum 16 of a second, different
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`material, with the two different materials functioning to release the contents of the
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`associated compartment under different conditions, eg under different conditions of pH, or
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`after different time intervals etc. For example, the first material may comprise pectin and
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`the second material may comprise HPMC. As a further example, the first material may
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`comprise tin-coated HPMC and the second material may comprise a HPMC coated, eg
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`with sodium alginate. Another possibility is for the first and second materials to have
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`different coatings, eg of sodium alginate and gum arabic. A yet further possibility is for
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`the first material to be expanded HPMC, with the second material being standard cast
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`HPMC coated with sodium alginate.
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`WO 01103676
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`PCTIGBOOIIJZfil 6
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`9
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`It is also possible for septum 16 to be of completely insoluble material that will. eg, pass
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`through the body unchanged.
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`The dimensions of capsule 10 may be varied to suit the intended purpose of the capsule.
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`with the maximum dimension typically being in the range 3m to 20mm.
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`Examples
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`The following examples serve to give specific illustrations of this invention but they are
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`not in any way intended to limit the scope of this invention.
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`Example 1. A dual delivery capsule as showu in Figure 1 where the septum 16. and the
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`capsule walls 12 and 14 are of like material, exampled by hydroxy propyl methyl
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`cellulose.
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`Example 2. A dual delivery capsule as shown in Figure 1 with one wall and dividing
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`septum of like material, exampled by hydroxy propyl methyl cellulose, and the other wall
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`of different material, exampled by pectin.
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`Example 3. A dual delivery capsule as shown in Figure 1 with walls and dividing septum
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`of like material, exampled by hydroxy propyl methyl cellulose with a coating on one half
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`of the capsule and one side of the capsule dividing septum, exampled by sodium alginate.
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`Example 4. A dual delivery capsule as shown in Figure 1 with walls and dividing septum
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`of like material, exampled by hydroxy propyl methyl cellulose with the same coating on
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`both sides of the capsule, exampled by sodium alginate.
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`Example 5. A dual delivery capsule as shown in Figure 1 with walls 12 and 14 of like
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`material exampled by hydroxy propyl methyl cellulose with different coatings on each
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`exampled by sodium alginate and gum arabic and dividing septum 16 coated on the side
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`closest to the wall bearing the alginate coating with gum arabic.
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`WO 01103676
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`PCTIG 1300392616
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`10
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`Example 6. A dual delivery capsule as shown in Figure 1 with a liquid fill contained in
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`chamber 20 exampled by
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`dextromethorphan and
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`a powder
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`filled example
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`by
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`chlopheniramine contained in chamber 18 between septum l6 and capsule wall 12.
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`Example 7. A dual delivery capsule as shown in Figure l with two different liquid fills
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`cxampled by cod liver oil and evening primrose oil contained in chamber 20 and chamber
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`18, respectively.
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`Figure 2 illustrates schematically one embodiment of apparatus for producing capsules in
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`accordance with the invention.
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`The illustrated encapsulation apparatus comprises two similar, aligned.
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`side-by~side
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`vacuum belts 40 and 42 each comprising a plurality of articulated segments of plastics-
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`coated aluminium as represented by segment 44. Each segment has a width of about
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`600mm, extending perpendicular to the plane of the sectional view of Figure 2. and is
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`formed with a row of hemi-ovoid recesses running across its width, eg recess 46, only one
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`such recess of each segment being visible in the drawing. Drive means (not shown) are
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`provided for driving the two belts synchronously, with belt 40 being driven in a clockwise
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`direction and belt 42 being driven in an anticlockwise direction, with the recesses of the
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`two belts in registration with each other. Each recess includes a number of fine bore
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`vacuum ports (not shown), each about 0.4mm in diameter, with vacuum means (not
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`shown) arranged to apply a vacuum in the range -15 to -30 inches mercury. The vacuum
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`may be applied only to the recesses in the segments when in the upper portion of travel of
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`the belts.
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`Four rolls of film material 50, 52, 54 and 56 are rotatably Supported on respective
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`spindles, with the films being pulled from the spindles and over vacumn belts by a driven
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`nip roller 58. The films pass around respective guide rollers 60, 62, 64, 66 to be brought
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`into contact with the associated vacuum belt.
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`W0 [lli03676
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`PCTIGBIIOIOZGIIS
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`11
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`Films 50 and 52 form the generally hemi-ovoid outer shell halves of a capsule. To this
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`end, the films pass below respective infra red heaters 68 and 70 located near the outer end
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`of each vacuum bed, which act to heat the film passing there below to a temperature at
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`which it is capable of deforming plastically. The films then deform to take up the shape of
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`the recesses in the vacuum belts, assisted by the vacuum applied to the belts.
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`The films, moving with the vacuum bed, then pass below respective adhesive application
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`stations 72, 74 in the form of rollers which apply adhesive to the surface of the films not
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`within the recesses.
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`The films then move past respective filling stations 76, 78 where metered doses of material
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`are supplied to each outer shell half as it passes below the station.
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`Suitable filling
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`equipment for supplying metered doses of liquid materials (eg syringe pumps. peristaltic
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`pumps etc) and for supplying metered doses of powdered or particulate materials are well
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`known. Typical volume fills are in the range 0.1 to 3.0 mls per capsule half.
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`The filled outer shell halves then move inwardly with the vacuum bed, past guide rollers
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`64, 66 around which pass lengths of septum-forming films 54, 56. The septum-forming
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`films adhere to the non—deformed parts of films 50 and 52 under the action of the
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`previously applied adhesive, closing off the half capsules.
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`The thus formed half capsules move inwardly with the vacuum belt past further adhesive
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`stations 80, 82 which act to apply adhesive to the top surface of the septum-forming fihns.
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`The capsule halves are brought together between adjacent sides of the vacuum belts and the
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`two septums adhere together by adhesive action. At this point, the capsules are loosely
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`stuck together.
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`The films with arrays of capsules therebetween are fed to a sealing station cornprising two
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`heater blocks 88, 90 mounted on pneumatic rams that reciprocate towards and away from
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`each other in synchronism. The blocks act to heat and fully seal together the capsule
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`W0 01.303676
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`PCTfGBOOr‘flZfil 6
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`12
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`halves, forming compartmented capsules in accordance with the invention. A knife edge
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`(not shown) is provided on one of the blocks to cut the capsules from the remaining
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`material. The cut capsules are collected below and the remaining film web material
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`is
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`passed to waste.
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`In a typical embodiment the films comprise HPMC having a thickness of about 120nm.
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`Such material is readily available commercially. For example, HPMC is available from
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`Dow Chemicals (USA) and is made into a film by Cast Film Technologies (USA).
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`Optional coatings may be applied to the film material, eg upstream of the rollers.
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`Different coatings may be applied to the different half-capsule forming films.
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`When treating HPMC, the films should be heated at heating stations to a temperature of
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`about 85 to 90°C so as to became thermoplastic and deformable.
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`A suitable adhesive for use with HPMC is HPMC with 60% propylene glycol, which can
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`be applied warm or cold. Other possible adhesivefplasticizer materials include triacetin.
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`monoacetin and ethyl lactate.
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`The adhesive formulation can also be applied before the forming heaters provided that it is
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`of food grade and there is no reactiou with the capsule contents.
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`In such a case there will
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`be a continuous coating of the adhesive present inside the formed capsule half. This can
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`help with adhesion of the septmn—forming film by causing a build up inside the seam.
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`For sealing HPMC, the heating block should be heated to a temperature in the range 150
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`to 170°C.
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`When using PVA instead of HPMC, heater temperatures must be much higher, about
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`150°C to produce a thermoplastic film, with the heater block typically being heated to a
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`temperature in the range 160 to 200°C.
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`W0 011'03676
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`PCT16 3001'0261 6
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`13
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`The illustrated equipment can run at a rate capable of producing about 30,000 capsules per
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`hour with a web width of about 600m.
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`A typical embodiment uses expanded HPMC for one capsule half and standard cast HPMC
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`coated with sodium alginate for the other capsule half. The standard cast HPMC has a
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`thickness of about 120 micron with a coating of alginate in the range 2 to 10 microns
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`thick.
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`The application of the first adhesive is conveniently effected by rolling, extrusion or
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`spraying, preferably by use of a roller, while application of the secoud adhesive is
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`conveniently effected by a roller in contact with the film.
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`The capsules produced by the apparatus of Figure 2 have a form generally corresponding
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`to the capsule of Figure I, with septum 16 being constituted by two adhered together
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`layers of film 54 and 56. The capsules include a short peripheral median flange (not
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`shown in Figure I), aligned with and extending Outwardly from the position of septum 16,
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`constituted by portions of the four films 50, 52, 54, 56 adhered together to seal
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`the
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`compartments and capsule.
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`W0 01l03676
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`PCTIGBOOIOZGIG
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`14
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`$1111.“:
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`1. A delivery capsule having at least two separate chambers.
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`2. A capsule according to claim 1, wherein each chamber contains a different material.
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`3. A capsule according to claim 1 or 2, wherein each chamber contains a metered dose of
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`a material.
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`4. A capsule according to claim 1, 2 or 3, including a dividing wall or septum defining in
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`part two separate chambers.
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`5. A capsule according to claim 4, wherein the dividing wall or septum comprises two
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`layers of material adhered together.
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`6. A capsule according to claim 4 or 5, wherein the dividing wall or septum camprises a
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`median wall symmetrically arranged to form two chambers of similar size and shape.
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`7. A capsule according to any one of the preceding claims, formed from a heat-scalable
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`material that is capable of deforming plastically on heating andlor when partially solvated.
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`8. A capsule according to claim 6, wherein the capsule is formed from one or more
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`materials selected from hydroxy propyl methyl cellulose, pectin. polyethylene oxide.
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`polyvinyl alcohol, alginate, polycaprolactone, gelatinised starch basod materials.
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`9. A capsule according to claim 8. wherein at least part of the capsule material carries a
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`coating.
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`10. A capsule according to any one of the preceding claims, wherein said at least two
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`chambers are designed to release their contents under similar circumstances.
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`Page 15 of 20
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`W0 012'03676
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`PCTIGBOOIGZ616
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`15
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`11. A capsule according to any one of claims 1 to 9, wherein said at least two chambers
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`are designed to release their contents under different circumstances.
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`12. A capsule according to claim 11, wherein different chambers of the capsule are
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`defined at least in part by different materials.
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`13. A capsule according to any one of the preceding claims. wherein the capsule is
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`formed at least in part from hydroxy propyl methyl cellulose.
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`14. A capsule according to claim 13, wherein at least part of the hydroxy prepyl methyl
`
`cellulose is coated with alginate.
`
`15. A method of encapsulation comprising supplying two films of material capable of
`
`deforming plastically on heating andfor when partially solvated; heating the films andfor
`
`applying solvent;
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`forming the films into suitably shaped capsule portions; supplying
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`respective substances to be encapsulated to capsule portions of each film; supplying a film
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`of a dividing septum material to at least One of the filled capsule portions; sealing the
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`capsule portions and septum material together to form a capsule having at
`
`least
`
`two
`
`separate chambers.
`
`16. Encapsulation apparatus comprising means for supplying two films of material to an
`
`encapsulation unit; means for plastically defamn'ng each film to form suitably shaped
`
`capsule portions; means for supplying respective substances to be encapsulated to the
`
`respective capsule portions of each film; means for supplying a film of dividing septum
`
`material to at least one of the filled capsule portions; and means for sealing together the
`
`capsule portions and septum material to produce a capsule having at least two separate
`
`chambers.
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`Page 16 of 20
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`Page 16 of 20
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`PCTIGBOIJIGZfilé
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`1/1
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`Fig.1.
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`12
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`18
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`14
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`16
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`+10
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`20
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`Wo
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`"Mr8
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`Page 17 of 20
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`SUBSTITUTE SHEET (RULE 25)
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`Page 17 of 20
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`INTERNATIONAL SEARCH REPORT
`
`imam ‘aIApplloetlonNo
`PCT/GB [JO/02616
`
`a. CLASSIFICATIONOF umac‘r lumen
`IPC 7
`A61K9 48
`A61J3/O7
`
`Accordhg to International Patent Classification “PC! or to both national classification and iPC
`
`Mirimum documentation searched tolewiiication system followed by classification symbols)
`IPC 7
`AGIK A61J
`
`Documentation searched other than minimu'n documentation to the extent that such documents are included in the fields searched
`
`Electronic data base cmwited during the intemational eeardt (name 01 data baae and. where pracfiwl. search terms used:
`
`NPI Data, PAJ, EPO-Internal
`
`
`
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Citation at comment, with indication. where appropriate. or H'ln relevant passages
`
`EP 0 211 079 A (FUJISAHA PHARMACEUTICAL
`00., LTD.) 25 February 1987 (1987—02-25)
`the whole document
`
`page 10,
`
`line 17 —page 11,
`
`line 5
`
`NO 97 3553? A (BIOPROGRESS TECHNOLOGY
`LIMITED) 2 October 1997 (1997-10-02)
`cited in the application
`claims 1,4
`
`NO 00 2736? A (BIOPROGRESS TECHNOLOGY
`INTERNATIONAL INCORPORATED)
`18 May 2000 (2000—05—18)
`cited in the application
`page 6,
`line 11 - line 1?
`
`1-1,
`1042,16
`
`3,9,13,
`14
`
`8.9.13
`
`El Further documents are listed in the confirmation ol' box 0.
`' Special catogonee' of cited documents :
`_
`_
`_
`.
`_
`A dommentdefinngll'togoneralatateoltho artwhlchtanot
`e
`do
`to
`otparlicularrei
`'E' ”flier document but publidtod on or ”a" "1° international
`filing date
`‘L' doc-tenant men may wow doubts on priority ciaimle) or
`W9“ ‘9 ““3" to wk“ the wbafimfim’ °f another
`citation or other 5mm] reason ('5 mm“)
`'0' document referring to an oral disclosure. use. exhibition or
`olhot' means
`‘P' doctment published prior to the lrrtemalional filing date but
`leter than the priority date claimed
`
`E Patent famin members are rated in annex.
`.
`to and not in conflict mth' the application but
`orprlority
`'1" later documgtt pthllehed alter the international filing date
`-
`-
`.
`.
`pinned firderatandd'teprmtplaortheory mderlylng the
`'X' document of particular :elevame: the claimed invention
`cannot be oortatd‘ered novel or cannot be cormtde'ted to
`involve an Inventive step when the document is taken alone
`'Y' domnem oi particuar relevance: the ctaimed lrwantion
`cannot be considered to involve an inventive step when the
`dome-non! is combined with one or more other such docu—
`meme. such combination being ohtn'oue to a person skilled
`"1 “‘3 “-
`'E' doom-pent member of the some patent family
`
`Date oi the acluai completion of the Hen-rational search
`
`Date of mailing of the lntematianal mm report
`
`11 October 2000
`
`Name and melting address oi the ISA
`European Patent Office. P3. 581 B Patentiann 2
`Ni. - 2230 Hv Fliiawiit
`
`17/10/2000
`
`Authorized officer
`
`Tel. (+3140) 340-2040. Tx. 31 651 epo nl.
`Fax: 9314013404015
`Form Pcmsmw [em-Id duet: {Jot}! 1992}
`Page 18 of 20
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`B
`
`9112 s
`
`K
`
`page 1 of 2
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`Page 18 of 20
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`
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`INTERNATIONAL SEARCH REPORT
`
`0400mm DOCUMENTS CONSIDERED TO BE RELEVANT
`Citatim of document. with lmicafion.Mme appropriate. of tha m1 passages
`
`
`
`
`
`
`
`H0 00 28976 A (A. B. TECHNOLOGIES L. L. C. )
`25 May 2000 (2000——05—25)
`the whole document
`
` 1m al Amalie-flan Na
`
`PCT/EB [JO/02615
`
`
`
`
`
`
`Farm PCTHSAEW :mm 6 am ma] (July 1992}
`
`Page 19 Of 20
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`page 2 of 2
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`Page 19 of 20
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`
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`INTERNATIONAL SEARCH REPORT
`ImmflHanumllymm
`almumanbnuo
` Inunu
`PCT/GB 00/02616
`
`Patent document
`cited in search I’EDOH.
`
`Publication
`date
`
`Patent family
`ITIBI'I'IbeflS)
`
`Publication
`daie
`
`
`
`
`
`)-
`
`E? 211079
`A
`25-02-1987
`00
`8604501
`14-08-1986
`
`
`
` 2168597 A
`17-10-1997
`9708352 A
`04-01-2000
`BR
`
`
`CA
`2250397 A
`02-10-199?
`
`
`CZ
`9803079 A
`17-02-1999
`
`
`EP
`0889?10 A
`13-01~1999
`9844?2 A 28~09—1998
`
`
`
`
`
`3788800
`29-05-2000
`2343669
`1?—05-2000
`
`
`
`
`
`Form FC‘I‘IISAMO (want my mum [My 1N2}
`
`Page 20 of 20
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`Page 20 of 20
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