WO1990007326A1 - Compositions pharmaceutiques - Google Patents

Compositions pharmaceutiques Download PDF

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Publication number
WO1990007326A1
WO1990007326A1 PCT/GB1989/001547 GB8901547W WO9007326A1 WO 1990007326 A1 WO1990007326 A1 WO 1990007326A1 GB 8901547 W GB8901547 W GB 8901547W WO 9007326 A1 WO9007326 A1 WO 9007326A1
Authority
WO
WIPO (PCT)
Prior art keywords
suppository
mould
phase
attachment
flexible
Prior art date
Application number
PCT/GB1989/001547
Other languages
English (en)
Inventor
Oswald Morton
Koral Embil
Original Assignee
Edko Trading And Representation Company Limited
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
Priority claimed from GB888830406A external-priority patent/GB8830406D0/en
Application filed by Edko Trading And Representation Company Limited filed Critical Edko Trading And Representation Company Limited
Publication of WO1990007326A1 publication Critical patent/WO1990007326A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A61K9/025—Suppositories; Bougies; Bases therefor; Ovules characterised by shape or structure, e.g. hollow layered, coated
    • 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
    • A61J3/08—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of suppositories or sticks

Definitions

  • This invention relates to multiphase suppositories and a method and apparatus for their manufacture.
  • suppositories consist of a supporting base which is solid at room temperature but melts at just below body temperature to liberate into the anorectal region or the lower intestinal tract one or more active substances. On melting, the active substances are liberated virtually simultaneously.
  • suppositories have not previously been designed to achieve such sequential release.
  • a supportory is required to release medication at a particular location, as in the treatment of haemorrhoids, there is the problem that rectal pressure forces the suppository upwards and away from ano-rectal region.
  • a suppository to include an outer phase and one or more inner phases such that there is a predetermined delay between release of active substances on melting of the outer phase and release of further active substances from the inner phase(s).
  • a multiphase suppository comprising an outer phase of a suppository base containing at least one active component of the suppository and at least one inner phase containing at least one further active component of the suppository, whereby on melting of said outer phase by body heat after administration, the inner phase or phases subsequently release said further component or components, said suppository having one or more flexible linear atachments to assist location in the ano-rectal region.
  • the outer phase of suppository base will normally be a conventional suppository base melting at about 34-36°C.
  • the said inner phase(s) may also comprise a suppository base, in which case its melting point may be different from that of the outer phase and in many cases will be slightly higher, for example 1 C or 2 C higher.
  • the inner phase comprises a silicone oil intended to coat and protect the medicaments released by the outer phase
  • the inner phases may thus advantage ⁇ ously be encapulated in a suitable material which substantially prevents such diffusion.
  • Such encapsulat ⁇ ing substances may be designed to release their contents by rupture due to, for example, pressure, melting or dissolving.
  • Encapsulating materials rupturing by pressure include the microcapsule materials sold by NCR. While the suppository is at room temperature, the capsules will be protected against rupture by the resilience or rubber-like consistency of the conventional suppository base. When the suppository melts, however, this protection is removed and it is possible that the considerable pressure exerted by the walls of the lower intestine and anorectal region will ensure rupture.
  • Such capsules may be small capsules dispersed throughout the outer phase or they may exist in one or more cavities in the suppository either as multiple or single capsules.
  • Encapsulating materials which release their contents by melting include hard or soft gelatin, which are both conventional encapsulating materials. Gelatin based materials may also rupture by dissolving in body fluids.
  • the medicaments in the outer phase of suppository base and silicone oil in one or more inner phases may comprise a further suppositor base containing the silicone oil in dispersion or solution, where the silicone oil is capable of dissolving in the outer suppository base material there is the possibility of diffusion into the material on storage. It is preferred, therefore, for the silicone oil to be encapsulated to provide a carrier against diffusion, e.g. in soft or hard gelatin capsules as described above.
  • the silicone oil will preferably be polydialkyl- siloxane oil, more preferably polydimethylsiloxane.
  • Suitable medical grade silicone oils include Dow Corning 360 Medical Fluid.
  • the medicament(s) which may be present include astringents such as bismuth subgallate, local anaesthetics such as benzocaine or lignocaine and antiinflammatory steroids such as hydrocortisone acetate.
  • a method for the manufacture of multiphase suppositories according to the invention having at least one flexible linear attachment wherein part of the said attachment is inserted into a suppository mould before, after or simultaneously with insertion of at least one of said inner phases and molten suppository base is introduced therein to provide the said outer phase which on cooling sets and thus secures the attachment.
  • the linear attachment material is preferably a light woven fabric such as gauze which has the desired properties of friction and flexibility. Commercial gauze tubing is satisfactory.
  • the inner phase preferably comprises a single capsule, e.g. a soft gelatin capsule, which is positioned approximately centrally within the suppository mass.
  • the flexible attachment and inner phase may conveniently be introduced into the suppository mould using a plunger rod or tube to push a loop of the flexible attachment into the mould and to position the inner phase within the loop. It may be convenient to use a plunger tube which is wide enough to permit the inner phase, e.g. a gelatin capsule, to be delivered through the tube. Such a plunger tube may also serve as the delivery means for the outer phase of molten suppository mass, conveniently being provided with lateral apertures to allow the molten material to flow in without obstruction.
  • the mould as used in the method and apparatus of the invention will normally be one from which the suppositories may be removed without destroying the mould.
  • Figure 1 represents a mould filling machine according to the invention
  • Figure 2 represents in greater detail the filling system of the machine of Figure 1
  • Figure 3 shows a suppository according to the invention.
  • a conveyor belt 1 is driven intermittently by drive roll 2 in the direction of the arrow 3.
  • the belt 1 is in two parts, leaving a central slot 6.
  • the upper surface of the belt 1 is provided with transverse flanges except in the vicinity of the slot 6.
  • Drive rolls 4 serve to feed an empty blister pack strip into the slot 6 to be located with the filling parts thereof between adjacent pairs of flanges which are appropriately spaced for this purpose.
  • the blister pack 5 is shown in greater detail in Fig. 2 and comprises an essentially planar laminate of two plastics sheets each moulded to define half of the required suppository mould and an extended upper portion for retaining tubular gauze attached to the suppository.
  • An upper flange is provided and engages with the sides of the slot 6 to support the blister pack during filling.
  • Feed means 7 for tubular gauze 8 is provided at one side of the belt 1 and a reel 9 is mounted on a pneumatically operated traverse 10.
  • the reel feeds gauze 8 into a channel formed by two flanges during a stationary phase of the belt drive and returns across the belt after the latter has moved forward a distance from one blister pack unit.
  • the tubular gauze 8 is thus laid in a zig-zag fashion across the belt, the pairs of flanges being relatively narrowly spaced to ensure that the gauze 8 always overlaps the filling part of the blister pack beneath.
  • a gauze clamp 13 is mounted above the belt 1 and in each stationary phase descends to clamp the gauze 8 against the upper surface of the belt while rotating knives 12 at each side of the belt cut the gauze 8 to leave a cut length of gauze in the channel defined by the said pair of flanges.
  • a filling device 14 is positioned centrally over the belt. This is shown in detail in Fig. 2
  • a canula 15 is attached to a tube 16 which is conneted to a reservoir (not shown) for molten suppository base.
  • the canula 15 is vertically movable by a motor 17 and gear train 18, being synchronised to plunge downwards into the blister pack 5 during each stationary phase of the belt.
  • a capsule feed means 19 is provided which presents ovoid capsules with the long axis vertical, the endmost capsule being positioned over the filling port of the blister pack 5.
  • a suitably sized hole in the feed means 19 is positioned beneath the endmost capsule.
  • Optical or other sensing means may be provided to check for the presence of a capsule in the endmost position of the feed means 19. The capsules are fed continuously from a reservoir (not shown) into the feed means 19.
  • the canula 15 During each stationary phase of the belt, the canula 15, the diameter of which is less than that of the capsule, pushes the latter downwards onto the length of tubular gauze 8 which has been moved along the belt to the filling station 14.
  • the canula 15 pushes the capsule and gauze together down to a point which is approximately central in the suppository mould section of the blister pack 5 and molten suppository base is then injected via the canula 15 to fill the mould section.
  • the canula 15 is withdrawn to a position above the capsule feed and the next capsule moves into the end position.
  • means are provided for pushing the ends of the gauze 8 into the blister pack.
  • This comprises a plunger which is preferably hollow, which plunges into the blister pack 5 below during each stationary phase of the machine.
  • the filled blister pack 6 is sealed by application of an adhesive strip along the length of the upper flange thereof.
  • the canula 15 may be specially shaped at the end to ensure that the capsule does not block the flow of molten suppository base. It is thus possible to provide the rim of the canula with an irregular profile or to provide holes in the canula just above the rim. If necessary the canula 15 may be double walled, the inner wall serving to push the capsule while the molten base flows between the two walls. The canula tip may be shaped to direct the flow of molten base downward, whereby the mould is filled in an upward direction from the lowest point to ensure complete and homogeneous encapsulation of the capsule. In a still further embodiment, the canula 15 may be wide enough to contain an inner duct down which a capsule may be fed into the blister pack.
  • FIG. 3 shows a suppository made by the apparatus of Figures 1 and 2 consisting of an outer phase 20 surrounding an inner capsule 21 around which is wrapped the central part of a length of tubular gauze 22 the ends of which extend 10-15 cm.

Landscapes

  • 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)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un suppositoire à phases multiples comprenant une phase externe de base de suppositoire, qui contient au moins l'un des composants actifs du suppositoire, et au moins une phase interne contenant au moins l'un des autres composants actifs du suppositoire. Sous l'effet de la chaleur du corps, la phase externe fond, permettant alors à la(les) phase(s) interne(s) de relâcher le(s)dit(s) autre(s) composant(s). Le suppositoire est muni d'un ou plusieurs éléments de fixation pour le maintenir en place dans la région ano-rectale. On décrit également un procédé de fabrication pour de tels suppositoires à phases multiples ainsi qu'un appareil servant à leur production.
PCT/GB1989/001547 1988-12-30 1989-12-29 Compositions pharmaceutiques WO1990007326A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB888830406A GB8830406D0 (en) 1988-12-30 1988-12-30 Pharmaceutical compositions
GB8830406.8 1988-12-30
US36134389A 1989-06-05 1989-06-05

Publications (1)

Publication Number Publication Date
WO1990007326A1 true WO1990007326A1 (fr) 1990-07-12

Family

ID=26294789

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1989/001547 WO1990007326A1 (fr) 1988-12-30 1989-12-29 Compositions pharmaceutiques

Country Status (1)

Country Link
WO (1) WO1990007326A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2268149A (en) * 1992-06-12 1994-01-05 Carlsberg Tetley Brewing Ltd Pressurized beverage container with gas chamber
US5422117A (en) * 1990-06-28 1995-06-06 Edko Trading And Representation Company Ltd. Multiphase pharmaceutical formulations
WO1999032084A1 (fr) * 1997-12-22 1999-07-01 Edko Trading And Representation Company Limited Compositions de traitement d'affections cutanees et anorectales
US6492639B1 (en) 1997-03-27 2002-12-10 Hkr Sensorsysteme Gmbh Method and apparatus for recognizing properties of a sample based on mass spectroscopy

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3617851A1 (de) * 1986-05-27 1987-12-03 Christensen Plantorgan Werk Suppositorium mit tampon zur behandlung von haemorrhoiden und anderen analbereicherkrankungen
DE3636174A1 (de) * 1986-10-24 1988-04-28 Cito Pac Verpackungs Gmbh Suppositorien-fuellstation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3617851A1 (de) * 1986-05-27 1987-12-03 Christensen Plantorgan Werk Suppositorium mit tampon zur behandlung von haemorrhoiden und anderen analbereicherkrankungen
DE3636174A1 (de) * 1986-10-24 1988-04-28 Cito Pac Verpackungs Gmbh Suppositorien-fuellstation

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5422117A (en) * 1990-06-28 1995-06-06 Edko Trading And Representation Company Ltd. Multiphase pharmaceutical formulations
GB2268149A (en) * 1992-06-12 1994-01-05 Carlsberg Tetley Brewing Ltd Pressurized beverage container with gas chamber
US6492639B1 (en) 1997-03-27 2002-12-10 Hkr Sensorsysteme Gmbh Method and apparatus for recognizing properties of a sample based on mass spectroscopy
WO1999032084A1 (fr) * 1997-12-22 1999-07-01 Edko Trading And Representation Company Limited Compositions de traitement d'affections cutanees et anorectales
GB2349819A (en) * 1997-12-22 2000-11-15 Edko Trading Representation Compositions for the treatment of skin and anorectal conditions

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