EP0228067A2 - Capsules molles sans soudure - Google Patents

Capsules molles sans soudure Download PDF

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Publication number
EP0228067A2
EP0228067A2 EP86117918A EP86117918A EP0228067A2 EP 0228067 A2 EP0228067 A2 EP 0228067A2 EP 86117918 A EP86117918 A EP 86117918A EP 86117918 A EP86117918 A EP 86117918A EP 0228067 A2 EP0228067 A2 EP 0228067A2
Authority
EP
European Patent Office
Prior art keywords
stream
film
composite jet
forming
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP86117918A
Other languages
German (de)
English (en)
Other versions
EP0228067B1 (fr
EP0228067A3 (en
Inventor
Tadashi Kosaka
Kazuki Omata
Tatsuo Hashimoto
Teruaki Yamazaki
Kazuo Hayashi
Tomiya Hosoi
Kenichi Ikuta
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taisho Pharmaceutical Co Ltd
Original Assignee
Taisho Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Priority to AT86117918T priority Critical patent/ATE67401T1/de
Publication of EP0228067A2 publication Critical patent/EP0228067A2/fr
Publication of EP0228067A3 publication Critical patent/EP0228067A3/en
Application granted granted Critical
Publication of EP0228067B1 publication Critical patent/EP0228067B1/fr
Expired legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use

Definitions

  • This invention relates to a seamless soft capsule, and more specifically, to a seamless soft capsule having a multicellular structure, and a method of its production.
  • a multicellular soft capsule having its inside partitioned by a film was recently proposed (see Japanese Laid-Open Patent Publication No. l09520/l985).
  • This patent document states that the multicellular soft capsule is obtained by partitioning a soft capsule shell composed of an upper film and a lower film into two cells by means of a partitioning film, and filling different drugs into the two cells.
  • two drugs which are not desired to be mixed can be stably included in a single soft capsule.
  • materials having different solu­bilities and dissolving speeds it is possible to cause one part of a single capsule to be released and absorbed in the stomach and the other part, in the intestines. It is also possible to make one part of the capsule fast-­releasing and the other part slow-releasing.
  • the capsule shell Since the proposed multicellular soft capsule is produced by a rotary method or a flat plate method, the capsule shell has seams. Hence, in spite of the aforesaid advantages, it has the defect that the filled drugs leak from the seams, or air comes through the seams to deteri­orate the contents oxidatively. Furthermore, by the rotary method or the flat plate method, it is difficult to produce multicellular soft capsules having a small size, and moreover, the cost of production becomes high. Fur­thermore, since both surfaces of the partitioning film in the aforesaid muticellular soft capsule are formed of the same material, if a drug to be filled in one of the cells reacts with the components of the partitioning film, it cannot be included in such a capsule.
  • Another object of this invention is to provide a simple and inexpensive method of producing the aforesaid seamless soft capsule, which can easily give capsules of a small size as well.
  • a soft capsule composed of a plurality of cells coalesced to each other and filling substances encapsulated in the individual cells, the wall of at least one of the cells being formed of a material different from a material forming the wall of at least one of the other cells, and said capsule being seamless.
  • the seamless soft capsule of this invention is produced by a method which comprises
  • the reference numeral l represents a tank holding a film-forming liquid substance A for forming a cell wall; 2, a tank holding a film-forming substance B which is different from the substance A; 3, a tank holding a filling substance C; and 4, a tank holding another filling substance D.
  • the tanks l, 2, 3 and 4 are individually provided with heating means (not shown) for maintaining the substances A, B, C and D at suitable temperatures for maintaining them flowable.
  • the sub­stances A, B, C and D are supplied to the tanks l, 2, 3 and 4 respectively.
  • Metering pumps ll, 2l, 3l and 4l are provided for feeding the substances A, B, C and D of the tanks l, 2, 3 and 4 to a composite nozzle 5.
  • the com­posite nozzle 5 is a duplex nozzle consisting of outside nozzles 5l and 52 having a semielliptical cross sectional shape resulting from par­titioning an elliptical tube by a partitioning wall 50 at its center and inside nozzles 5a and 5b of a smaller diameter disposed nearly centrally in the outside nozzles 5l and 52 respectively.
  • the outside nozzles 5l and 52 communicate with the tanks l and 2, and the inside nozzles 5a and 5b, with the tanks 3 and 4.
  • the composite nozzle 5 faces downwardly along a downwardly flowing stream of a liquid medium e within a capsule-forming tank 6.
  • the specification of the composite nozzle 5 may be freely changed according, for example, to the use of the capsule to be produced.
  • a typical specifi­cation is that in Figure 2, the elliptical tube has an outside long diameter d l of 5 to 20 mm and an outside short diameter d s of 3 to l2 mm, and the inside nozzles have an outside diameter of d i of 2 to 9 mm, and the individual tubes have a thickness of 0.l to 2 mm.
  • the liquid medium e formed, for example, of liquid paraffin is sent to a heat exchanger 72 from a recovery hopper 7 concurrently acting as a storage tank by means of a pump 7l.
  • a heat exchanger 72 it is cooled to a moderate temperature of, for example, about 5°C and supplied to the upper portion of the capsule-­forming tank 6. It becomes a downwardly flowing stream within the capsule-forming tank 6, and is circulated to the recovery hopper 7 via a capsule recovery tube 6l.
  • a part of the liquid medium e is supplied to a pulse stream-­forming device 74 by means of a pump 73 from the hopper 7. It is converted to a regular pulse stream in the pulse stream-forming device 74 and supplied to a pulse stream nozzle 8 provided within the capsule-forming tank 6.
  • the pulse stream nozzle 8 is a circular nozzle provided immediately below, and coaxially with, the com­posite nozzle 5 and having a slightly larger diameter than the diameter of the elliptical tube of the composite nozzle 5.
  • a pulsating stream of the liquid medium e from the nozzle 8 is extruded toward the center of the nozzle 8 from an annular slit formed within the nozzle 8 in such a manner as to surround a single composite jet stream formed by the composite nozzle 5
  • Film-forming liquid substances A and B for cell wall formation and filling substances C and D to be filled in a capsule are sent under pressure to nozzles 5l, 52, 5a and 5b constituting the composite nozzle 5 by means of the metering pumps ll, 2l, 3l and 4l.
  • a composite jet stream composed of a stream of the film-form­ing substance A and a single stream of the filling sub­stance C is extruded into, and along, the downwardly flowing liquid medium flow within the capsule-forming tank 6, and from the nozzle 52, a composite jet stream composed of a stream of the film-forming substance B and a stream of the filling substance D is likewise extruded into, and along, the downwardly flowing liquid medium stream within the capsule-forming tank 6.
  • the two composite jet streams extruded as above, nearly simul­taneously with their formation, are coalesced to each other into a single composite jet stream within the down­wardly flowing stream of the liquid medium e owing to the surface tensions of the film-forming liquid substances A and B.
  • the speeds of extruding the composite jet streams, and the flow rate of the downwardly flowing stream of the liquid medium e can be varied depending upon, for example, the types of the film-forming liquid substances forming the composite jet streams, the type of the liquid medium e and the size of the composite nozzle, and any skilled person in the art would be able to de­termine optimum conditions easily by routine experiments.
  • the jet stream is drawn downwardly by the downwardly flowing stream of the liquid medium e , and successively cut off at the neck portions by the downwardly drawing force.
  • Each cut drop­let f contains the filling substances C and D encapsulated in the film-forming liquid substances A and B by the surface tension of the substances A and B, and is formed into a seamless capsule, which is roundish as a whole, while moving down through the downwardly flowing stream of the liquid medium e .
  • the capsules formed advance to the hopper 7 via the recovery tube 6l while being cooled and solidified.
  • the capsules are separated from the liquid medium e by a separator 70, supplied to a conveyor 9 provided on one side of the separator 70, and sent to a drying step where they are dried to produce a final product.
  • the film-forming substance for cell formation may be any material which can be formed into a thin film from its melt or solution, and after film formation can be solidified by cooling and/or drying.
  • Substances usually employed in forming the shell of a soft capsule may be used in this invention. Examples include film-forming substances composed of gelatin or gelatin derivatives such as succinic gelatin and incorporated therein, plasticizers [such as glycerol, sorbitol, propylene glycol and Carbowax (polyethylene glycol)], essences and flavors (such as peppermint oil, cinnamon oil and strawberry), dyes (such as yellow No. 4, yellow No. 5, red No. l, blue No.
  • opacifying agents such as titanium dioxide and red iron oxide
  • solubility controlling agents such as cellulose acetate phthalate, alkali metal salts of hydroxypropylmethyl cellulose, alkali metal salts of hydroxymethyl cellulose acetate succinate, alkali metal salts of alginic acid, alkali metal salts of polyacrylic acid, methyl cellulose, carboxymethyl cellulose, casein, collagen, agar powder, polyvinyl alcohol and pectin)), etc. selected as desired. It is generally used as a liquid by dissolving it in water under heat.
  • the filling substance to be encapsulated in each cell of the soft capsule of this invention can be any drug which does not dissolve the cell wall nor react with the components of the cell wall. It is preferably liquid when it is to be filled in the cell in accordance with the method of this invention. Accordingly, when the drug is a solid, it is desirably filled in a flowable state as a solution, emulsion or suspension.
  • At least one of a plurality of cells constituting the resulting soft capsule can have a different dissolving time in the digestive tract from at least one of the other cells (for example, whether fast-releasing or slow-releasing), or at least one cell may have different dissolving character­istic from at least one of the other cells (for example, whether released and adsorbed in the stomach or the intestines).
  • the filling substances to be encapsulated in the cells may be varied from cell to cell.
  • a single capsule may be obtained in which a drug expected to be fast-acting is filled in a fast-dissolving cell and a drug desired to be slow-acting is filled in a slow-dissolving cell.
  • a single capsule cell may be obtained in which a drug expected to develop its effect in the stomach is filled in a cell soluble at the stomach, and another drug expected to develop its effect in the intestines is filled in a cell soluble at the intestines.
  • the shape of the soft capsule l0 can be selected by changing the shape of the end surface of the composite nozzle 5 on the extrusion side. Some modified examples of the composite nozzle 5 will be described below.
  • the composite nozzle 5 shown in Figure 4 is composed of duplex outside nozzles 5l and 52 having a cocoon-shaped cross section and smaller-diameter inside nozzles 5a and 5b disposed coaxially within the outside nozzles 5l and 52 respectively.
  • the capsule l0 obtained by using this composite nozzle 5 has a cocoon-shaped cross-section as shown in Figure 5. It is a seamless soft capsule in which filling substances c and d are independ­ently encapsulated in cells a and b .
  • Figures 6 and 8 show other examples of the composite nozzle 5. These nozzles 5 are each divided into three outside nozzles 5l, 52 and 53 by two or three par­titioning walls 50 and smaller-diameter inside nozzles 5a, 5b and 5c are disposed centrally in the outside nozzles 5l, 52 and 53 respectively.
  • Figure l0 shows still another example of the composite nozzle 5 in which a large-diameter tube of an elliptical cross-sectional shape is divided into a large-­diameter outside nozzle 5l and a small-diameter outside nozzle 52 by a partitioning wall 50 at a site about l/3 as viewed from one end surface of the tube, inside nozzles 5a and 5b having a smaller diameter are disposed in the large-diameter outside nozzle 5l in spaced-apart relation­ship, and an inside nozzle 5c having a smaller diameter is disposed centrally in the small-diameter outside nozzle 52.
  • the soft capsule l0 produced in this way is a seamless soft capsule composed of a unitary structure of a cell a and two filling substances c and h independently encapsulated in it and a cell b and one filling substance d encapsulated in it, as shown in Figure ll.
  • the soft capsule l0 shown in Figure ll and the method of production using the composite nozzle shown in Figure l0 give a caspsule in which two filling substances c and h are independently encapsulated in a cell having a cell wall of the same material. Hence, they are bene­ficial when different drugs which are to be released simultaneously from one cell a but should not be mixed beforehand are used as the filling substances c and h .
  • the single composite jet stream formed along the flow of the liquid medium e may be cut to a predetermined length from its leading end in the flowing direction by intermittently increasing the speed of the downwardly flowing stream of the liquid medium e , and intermittently pulling off the composite jet stream downwardly by the quickened downwardly flowing liquid stream, instead of applying a pulsating flow of the liquid medium e sideways to the composite jet stream in the embodiments described above.
  • the single composite jet stream can be cut successively to a pre­determined length.
  • one capsule con­tains a plurality of cells whose cell walls are made of different materials.
  • the present invention is suitable for filling both a substance to be released and absorbed in the stomach and a substance to be released and absorbed in the intestines, or at least two substances having different dissolving times, in a separated state in a single capsule. Since the soft capsule of the invention is seamless, the filled substances can be retained stably while preventing their deterioration by oxidation or otherwise.
  • capsules of any desired sizes can be produced, and capsules having a smaller size than in the prior art can be easily produced at low cost.
  • a film-forming substance A was filled in tank l, and a film-forming substance B, in tank 2.
  • These film-forming substances A and B were ex­truded from composite nozzle 5 having a outside long diameter (d l ) of l3 mm, an outside short diameter (d s ) of 9 mm and a thickness of l mm ( Figure 2) by metering pumps ll and 2l.
  • the amount of each of the film-forming sub­stances A and B was 65.7 g/min.
  • a filling substance C was filled in tank 3, and another filling substance D, in tank 4.
  • the filling substances C and D were extruded from nozzles 5a and 5b having an outside diameter (di) of 3 mm, an inside diameter of 2 mm and a thickness of 0.5 mm ( Figure 2) by metering pumps 3l and 4l.
  • the amount of each of the filling substances extruded was 36 g/min.
  • Composite jet streams composed of the film-forming sub­tances A and B and the filling substances C and D flowed at a rate of l0 meters/min.
  • a paraffin oil as a cooling medium e within vessel 7 and heat-exchanger 72 was maintained at 3°C, and flowed downwardly in capsule-forming tank 6 at a flow rate of l5 m/min.
  • a pulsating flow of the paraffin oil gene­rated from pulse flow generator 74 was extruded at equal time intervals from pulse flow nozzle 8 accurately l5 times per second.
  • capsules were formed at a rate of l5 per second at intervals of about ll mm. After drying, each of the caspsules had a long dia­meter of 8 mm and a short diameter of 6 mm, and the amount of each of the filling substances was 40 mg per capsule.
  • the film-forming substance A is a solution consisting of 20 parts of gelatin, 5 parts by weight of glycerol, 8 parts by weight of sorbitol and 67 parts by weight of purified water which was maintained at about 60°C.
  • the film-forming substance B was a solution consisting of l8 parts by weight of gelatin, 5 parts by weight of glycerol, 2.5 parts by weight of sodium alginate and 74.5 parts by weight of purified water which was maintained at about 60°C.
  • the filling substances C and D were solutions composed of different drugs which were maintained at about 25°C.
  • the film a dissolved in several minutes to release the core c , whereas the film b did not dissolve for more than 2 hours.
  • both the films a and b dissolved within 2 to 3 minutes.
  • film-forming substances A and B were extruded from a composite nozzle having an outside long diameter (D l ) of 7.5 mm, an outside short diameter (D s ) of 3.5 mm and a thickness of 0.5 mm.
  • the amount of each of the film-forming substances A and B extruded was 2l.9 g/min.
  • filling substances C and D were extruded extruded from nozzles 5a and 5b having an outside diameter (d i ) of l mm and a thickness of 0.l mm.
  • the amount of each of the substances C and D extruded was l8.6 g/min.
  • the speed of the composite jet stream at this time was 6 m/min.
  • a paraffin oil was used as a cooling medium e and caused to flow in capsule-forming tank 6 at a rate of 22.5 m/min.
  • a pulsating flow of the paraffin oil generated from the pulse stream generator 74 was extruded from pulse stream nozzle 8 at equal time intervals accurately 50 times per second.
  • capsule-forming tank 6 fifty capsules were formed per second at intervals of about 7.5 mm. After drying, each of the capsule had a long diameter of 3.5 mm and a short diameter of 2.5 mm. The amount of each of the filling substances C and D was about 6.2 mg.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Rigid Containers With Two Or More Constituent Elements (AREA)
  • Wrappers (AREA)
EP86117918A 1985-12-26 1986-12-23 Capsules molles sans soudure Expired EP0228067B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT86117918T ATE67401T1 (de) 1985-12-26 1986-12-23 Weiche nahtlose kapseln.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP29718285 1985-12-26
JP297182/85 1985-12-26

Publications (3)

Publication Number Publication Date
EP0228067A2 true EP0228067A2 (fr) 1987-07-08
EP0228067A3 EP0228067A3 (en) 1988-06-01
EP0228067B1 EP0228067B1 (fr) 1991-09-18

Family

ID=17843233

Family Applications (1)

Application Number Title Priority Date Filing Date
EP86117918A Expired EP0228067B1 (fr) 1985-12-26 1986-12-23 Capsules molles sans soudure

Country Status (6)

Country Link
EP (1) EP0228067B1 (fr)
JP (1) JPH06104193B2 (fr)
AT (1) ATE67401T1 (fr)
DE (1) DE3681572D1 (fr)
ES (1) ES2024418B3 (fr)
GR (1) GR3002754T3 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0585368A1 (fr) * 1991-04-25 1994-03-09 Univ Brown Res Found Vehicule implantable immuno-isolateur et biocompatible servant a apporter des produits therapeutiques selectionnes.
US5800829A (en) * 1991-04-25 1998-09-01 Brown University Research Foundation Methods for coextruding immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core
GB2338896A (en) * 1998-07-02 2000-01-12 Reckitt & Colmann Prod Ltd Chewable oral dosage unit with multilpe reservoirs
WO2001054645A1 (fr) * 2000-01-26 2001-08-02 Jongkang Yi Machine a emballer des capsules molles
WO2003094897A1 (fr) * 2002-05-09 2003-11-20 Chugai Seiyaku Kabushiki Kaisha Capsule souple photostabilisee
WO2004024057A1 (fr) * 2002-09-13 2004-03-25 Freund Corporation Procede de production d'une capsule sans soudure se dissolvant rapidement dans la cavite orale
US7025911B2 (en) 2002-09-13 2006-04-11 Freund Corporation Manufacturing method for oral quick-dissolving seamless capsule
WO2007066178A2 (fr) * 2005-12-08 2007-06-14 Mcneil-Ppc, Inc. Compositions et capsules avec des couches hydrophiles stables
US7670612B2 (en) 2002-04-10 2010-03-02 Innercap Technologies, Inc. Multi-phase, multi-compartment capsular delivery apparatus and methods for using same
US7691407B2 (en) 1999-07-30 2010-04-06 Smithkline Beecham Plc Multi-component pharmaceutical dosage form

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0102342D0 (en) 2001-01-30 2001-03-14 Smithkline Beecham Plc Pharmaceutical formulation
US7883721B2 (en) 2001-01-30 2011-02-08 Smithkline Beecham Limited Pharmaceutical formulation
EP1608347B1 (fr) * 2003-03-28 2014-08-13 Sigmoid Pharma Limited Forme posologique solide s'administrant par voie orale qui contient des microcapsules sans soudure
TW200526274A (en) 2003-07-21 2005-08-16 Smithkline Beecham Plc Pharmaceutical formulations
JP4051075B2 (ja) * 2003-11-07 2008-02-20 フロイント産業株式会社 シームレスカプセル製造方法、シームレスカプセル製造装置及びシームレスカプセル
PE20060003A1 (es) 2004-03-12 2006-03-01 Smithkline Beecham Plc Formulacion farmaceutica polimerica para moldear por inyeccion
JP5183104B2 (ja) * 2006-06-19 2013-04-17 森下仁丹株式会社 口臭除去用多重ソフトカプセル
US20090297455A1 (en) * 2006-08-09 2009-12-03 Koninklijke Philips Electronics N.V. Device for and a method of activating a physiologically effective substance by ultrasonic waves, and a capsule
JP2009119148A (ja) * 2007-11-16 2009-06-04 Freunt Ind Co Ltd 多色シームレスカプセルの製造装置及び製造方法
JP6050759B2 (ja) * 2011-11-16 2016-12-21 森下仁丹株式会社 害虫駆除剤
JP6091679B1 (ja) * 2016-03-29 2017-03-08 株式会社松風 液滴生成装置

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0116311A1 (fr) * 1983-01-17 1984-08-22 Morishita Jintan Co., Ltd. Capsules molles doubles et leur production
JPS60109520A (ja) * 1983-11-16 1985-06-15 Fujisawa Pharmaceut Co Ltd 多室軟カプセル剤
JPS61151119A (ja) * 1984-12-24 1986-07-09 Taisho Pharmaceut Co Ltd ソフトカプセル

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0116311A1 (fr) * 1983-01-17 1984-08-22 Morishita Jintan Co., Ltd. Capsules molles doubles et leur production
JPS60109520A (ja) * 1983-11-16 1985-06-15 Fujisawa Pharmaceut Co Ltd 多室軟カプセル剤
JPS61151119A (ja) * 1984-12-24 1986-07-09 Taisho Pharmaceut Co Ltd ソフトカプセル

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN, Band 10, Nr. 350 (C-387)[2406], 26th November 1985; & JP-A-61 151 119 (TAISHO PHARMACEUT CO. LTD.) 09-07-1986 *
PATENT ABSTRACTS OF JAPAN, vol. 9, no. 254 (C-308)[1977], 11th October 1985; & JP-A-60 109 520 (FUJISAWA YAKUHIN KOGYO) 15-06-1985 *

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6322804B1 (en) 1991-04-25 2001-11-27 Neurotech S.A. Implantable biocompatible immunoisolatory vehicle for the delivery of selected therapeutic products
EP0585368A4 (fr) * 1991-04-25 1994-04-13 Brown University Research Foundation
EP0585368A1 (fr) * 1991-04-25 1994-03-09 Univ Brown Res Found Vehicule implantable immuno-isolateur et biocompatible servant a apporter des produits therapeutiques selectionnes.
US5800828A (en) * 1991-04-25 1998-09-01 Brown University Research Foundation Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products
US5800829A (en) * 1991-04-25 1998-09-01 Brown University Research Foundation Methods for coextruding immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core
US5834001A (en) * 1991-04-25 1998-11-10 Brown University Research Foundation Methods for making immunoisolatory implantable vehicles with a biocompatiable jacket and a biocompatible matrix core
US5869077A (en) * 1991-04-25 1999-02-09 Brown University Research Foundation Methods for treating diabetes by delivering insulin from biocompatible cell-containing devices
US5871767A (en) * 1991-04-25 1999-02-16 Brown University Research Foundation Methods for treatment or prevention of neurodegenerative conditions using immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core
US5874099A (en) * 1991-04-25 1999-02-23 Brown University Research Foundation Methods for making immunoisolatary implantable vehicles with a biocompatible jacket and a biocompatible matrix core
US6960351B2 (en) 1991-04-25 2005-11-01 Brown University Research Foundation Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products
US6083523A (en) * 1991-04-25 2000-07-04 Brown University Research Foundation Implantable biocompatable immunoisolatory vehicle for delivery of selected therapeutic products
US5798113A (en) * 1991-04-25 1998-08-25 Brown University Research Foundation Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products
US6589551B1 (en) 1998-07-02 2003-07-08 Reckitt Benckiser Healthcare (Uk) Limited Chewable oral unit dosage
GB2338896B (en) * 1998-07-02 2003-05-21 Reckitt & Colmann Prod Ltd Chewable Capsules
GB2338896A (en) * 1998-07-02 2000-01-12 Reckitt & Colmann Prod Ltd Chewable oral dosage unit with multilpe reservoirs
US7691407B2 (en) 1999-07-30 2010-04-06 Smithkline Beecham Plc Multi-component pharmaceutical dosage form
WO2001054645A1 (fr) * 2000-01-26 2001-08-02 Jongkang Yi Machine a emballer des capsules molles
US8361497B2 (en) 2002-04-10 2013-01-29 Innercap Technologies, Inc. Multi-phase, multi-compartment, capsular delivery apparatus and methods for using the same
US7670612B2 (en) 2002-04-10 2010-03-02 Innercap Technologies, Inc. Multi-phase, multi-compartment capsular delivery apparatus and methods for using same
US8703182B2 (en) 2002-05-09 2014-04-22 Chugai Seiyaku Kabushiki Kaisha Light-stabilized soft capsule formulations
JPWO2003094897A1 (ja) * 2002-05-09 2005-09-08 中外製薬株式会社 光安定化軟カプセル剤
JP5105705B2 (ja) * 2002-05-09 2012-12-26 中外製薬株式会社 光安定化軟カプセル剤
WO2003094897A1 (fr) * 2002-05-09 2003-11-20 Chugai Seiyaku Kabushiki Kaisha Capsule souple photostabilisee
US7025911B2 (en) 2002-09-13 2006-04-11 Freund Corporation Manufacturing method for oral quick-dissolving seamless capsule
WO2004024057A1 (fr) * 2002-09-13 2004-03-25 Freund Corporation Procede de production d'une capsule sans soudure se dissolvant rapidement dans la cavite orale
WO2007066178A2 (fr) * 2005-12-08 2007-06-14 Mcneil-Ppc, Inc. Compositions et capsules avec des couches hydrophiles stables
WO2007066178A3 (fr) * 2005-12-08 2007-09-07 Warner Lambert Co Compositions et capsules avec des couches hydrophiles stables

Also Published As

Publication number Publication date
EP0228067B1 (fr) 1991-09-18
GR3002754T3 (en) 1993-01-25
JPH06104193B2 (ja) 1994-12-21
DE3681572D1 (de) 1991-10-24
ATE67401T1 (de) 1991-10-15
JPS62234542A (ja) 1987-10-14
ES2024418B3 (es) 1992-03-01
EP0228067A3 (en) 1988-06-01

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