GB2281204A - Sustained release morphine compositions - Google Patents

Sustained release morphine compositions Download PDF

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Publication number
GB2281204A
GB2281204A GB9315467A GB9315467A GB2281204A GB 2281204 A GB2281204 A GB 2281204A GB 9315467 A GB9315467 A GB 9315467A GB 9315467 A GB9315467 A GB 9315467A GB 2281204 A GB2281204 A GB 2281204A
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United Kingdom
Prior art keywords
hours
morphine
test
pharmaceutical composition
active ingredient
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.)
Withdrawn
Application number
GB9315467A
Other versions
GB9315467D0 (en
Inventor
Joanne Heafield
Trevor John Knott
Stewart Thomas Leslie
Sandra Therese Antoi Malkowska
Ronald Brown Miller
Derek Allan Prater
Kevin John Smith
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.)
Euro Celtique SA
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Euro Celtique SA
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 Euro Celtique SA filed Critical Euro Celtique SA
Priority to GB9315467A priority Critical patent/GB2281204A/en
Publication of GB9315467D0 publication Critical patent/GB9315467D0/en
Priority to IL10994494A priority patent/IL109944A/en
Priority to ES94304144T priority patent/ES2124372T5/en
Priority to SG1996009186A priority patent/SG50706A1/en
Priority to EP94304144A priority patent/EP0636370B2/en
Priority to AT94304144T priority patent/ATE172376T1/en
Priority to DK94304144T priority patent/DK0636370T4/en
Priority to DE69414046T priority patent/DE69414046T3/en
Priority to CZ19941550A priority patent/CZ287918B6/en
Priority to SK763-94A priority patent/SK280534B6/en
Priority to IN571MA1994 priority patent/IN183742B/en
Priority to NZ260883A priority patent/NZ260883A/en
Priority to PL94304062A priority patent/PL179282B1/en
Priority to FI943141A priority patent/FI114285B/en
Priority to CA002127166A priority patent/CA2127166C/en
Priority to AU66105/94A priority patent/AU6610594A/en
Priority to NO942470A priority patent/NO306449B1/en
Priority to KR1019940015740A priority patent/KR100365572B1/en
Priority to JP15121994A priority patent/JP3647897B2/en
Priority to HU9402007A priority patent/HU220075B/en
Publication of GB2281204A publication Critical patent/GB2281204A/en
Priority to US08/843,571 priority patent/US5879705A/en
Priority to AU52995/98A priority patent/AU722358B2/en
Priority to US09/264,399 priority patent/US6143328A/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

An orally administered sustained release dosage unit form containing morphine, or a pharmaceutically acceptable salt thereof, as active ingredient, which composition gives a peak plasma level at from 1.0 to 3.5 hours after administration. The morphine dosage form is suitable for once-a-day administration. It is preferably in the form of a capsule filled with pellets comprising morphine and a hydrophobic release control material such as a natural or synthetic wax or oil e.g. hydrogenated vegetable or castor oil.

Description

SUSTAINED RELEASE COMPOSITIONS This invention is concerned with improvements in and relating to sustained release compositions and, more particularly, is concerned with sustained release orally administerable dosage unit forms containing morphine, or a pharmaceutically acceptable salt thereof, as active ingredient.
Morphine is an opioid analgesic well established for use in the treatment of pain, especially moderate to severe pain. Morphine-containing compositions in sustained release form are currently commercially available as so-called "twice-a-day" formulations, that is formulations having a duration of activity of 12 hours or more and accordingly requiring to be administered twice a day.
It is an object of the present invention to provide a morphine-containing sustained release orally administrable dosage unit form which has an effective duration of activity of 24 hours or more and, hence, is suitable for administration on a once daily basis.
It has surprisingly been found, in accordance with the present invention, that effective therapeutic activity over a period of 24 hours or more may be obtained from a morphine-containing sustained release formulation which gives an in vivo peak plasma level relatively early after administration, that is from 1.0 to 3.5 hours after administration.
Accordingly, one embodiment of the invention provides an orally administrable sustained release dosage unit form containing morphine, or a pharmaceutically acceptable salt thereof, as active ingredient which formulation gives a peak plasma level at from 1.0 to 3.5 hours, preferably 2 to 3 hours, after administration.
When the morphine is administered as morphine sulphate and the method of plasma analysis is high performance liquid chromatography, the peak plasma level of morphine (per ml of plasma) is preferably from 0.5 x 10 7 to 7.5 x 10 7 times the amount of morphine sulphate orally administered. When morphine base or a salt other than the sulphate is administered, the preferred ratio of drug administered to peak plasma level should be adjusted according to the molecular weight of the base or salt.
The dosage unit form in accordance with the invention should contain sufficient morphine, or salt thereof, to give therapeutic activity over a period of at least 24 hours. The actual amount of morphine, or salt, in any particular dosage form will of course depend upon a number of variables including (i) the number of dosage unit forms intended to be administered at any one time and (ii) the intended dosage for any particular patient. Conveniently, however, dosage unit forms in accordance with the invention will contain from 10 to 500 mg of morphine (calculated as morphine sulphate) and thus, for example, typical dosage unit forms in accordance with the invention are those containing 20, 30, 60, 90, 120, 150 and 200 mg of morphine (calculated as above).
It has further been found, in accordance with the present invention, that in order to achieve the desired time of peak plasma level and to provide effective activity over a period of at least 24 hours, the in vitro release characteristics of the formulation [when measured by the modified Ph.Eur. Basket method at 100 rpm in 900 ml aqueous buffer (pH 6.5) at 37 C] are as set out below: hours after morphine (salt) released start of test suitable preferred 2 15-50 25-50 4 20-65 30-65 6 25-75 40-75 12 40-90 60-90 18 55-100 70-100 24 65-100 80-100 The compositions of the invention may be provided in a variety of forms, for example as tablets or capsules containing granules, spheroids or pellets.Commonly, the composition will comprise the active ingredient (morphine or salt thereof) together with a diluent which may serve to delay release of the active ingredient or which may be coated with a coating which serves to control the rate of release of the active ingredient. A preferred form of dosage unit form in accordance with the invention comprises a capsule filled with pellets essentially comprising the active ingredient and a hydrophobic release control material. In particular, the pellets are preferably prepared by a so-called "melt pelletisation" process.In essence, such process comprises forming a mixture of dry particulate active ingredient and fusible release control material and pelletising the mixture in a high speed mixer at a rate and energy input such that sufficient energy is supplied to the fusible material or melt or soften it whereby it forms pellets with the particulate active ingredient.
The resultant pellets, after cooling, are suitably sieved to give pellets having a particle size range from 0.1 to 3.0 mm, preferably 0.25 to 2.0 mm.
When using such a melt pelletisation technique it has been found that, in order to most readily achieve the desired release characteristics (.both in vivo and in vitro as discussed above) the composition to be pelleted should comprise two essential ingredients namely: (a) active ingredient (morphine or salt thereof); and (b) hydrophobic fusible carrier or diluent; optionally together with (c) a release control component comprising a water-soluble fusible material or a particulate soluble or insoluble organic or inorganic material.
The hydrophobic fusible component (b) should be a hydrophobic material such as a natural or synthetic wax or oil, for example hydrogenated vegetable oil or hydrogenated castor oil, and suitably has a melting point of from 35 to 100by, preferably 45 to 900C.
The release modifying component (c), when a water soluble fusible material, is conveniently a polyethylene glycol and, when a particulate material, is conveniently a pharmaceutically acceptable material such as dicalcium phosphate or lactose.
Only a relatively small amount of component (c) is required to modify the release characteristics of the formulation and thus, for example, this component suitably forms from 0.01 to 20% by weight, more preferably 0.01 to 15% by weight of the total weight of the pellets. We have found that the total amount of active ingredient in the composition may vary within wide limits, for example from 10 to 60% by weight thereof.
Alternatively the morphine (or salt thereof) may be formulated (e.g. by dry or wet granulation or by blending) in a controlled release mixture formed of components other than fusible components. Suitable materials for inclusion in a controlled release matrix include, for example (a) Hydrophilic or hydrophobic polymers, such as gums, cellulose ethers, protein derived materials, nylon, acrylic resins, polylactic acid, polyvinylchloride, starches, polyvinylpyrrolidones, cellulose acetate phthalate. Of these polymers, cellulose ethers especially substituted cellulose ethers such as alkylcelluloses (such as ethylcellulose), C1-C6 hydroxyalkylcelluloses (such as hydroxypropylcellulose and especially hydroxyethyl cellulose) and acrylic resins (for example methacrylates such as methacrylic acid copolymers) are preferred.The controlled release matrix may conveniently contain between 1k and 80% (by weight) of hydrophilic or hydrophobic polymer.
(b) Digestible, long chain (C8-C50, especially C8-C40), substituted or unsubstituted hydrocarbons, such as fatty acids, hydrogenated vegetable oils such as Cutina (Trade Mark), fatty alcohols (such as lauryl, myristyl, stearyl, cetyl or preferably cetostearyl alcohol), glyceryl esters of fatty acids for example glyceryl monostearate mineral oils and waxes (such as beeswax, glycowax, castor wax or carnauba wax). Hydrocarbons having a melting point of between 250C and 900C are preferred. Of these long chain hydrocarbon materials, fatty (aliphatic) alcohols are preferred. The matrix may contain up to 60% (by weight) of at least one digestible, long chain hydrocarbon.
(c) Polyalkylene glycols. The matrix may contain up to 60% (by weight) of at least one polyalkylene glycol.
A suitable matrix comprises one or more cellulose ethers or acrylic resins, one or more C12-C36 preferably C14-C22, aliphatic alcohols and/or one or more hydrogenated vegetable oils.
A particularly suitable matrix comprises one or more alkylcelluloses, one or more C12-C36, (preferably C14-C22) aliphatic alcohols and optionally one or more polyalkylene glycols.
Preferably the matrix contains between 0.5 and 60S, especially between 1% and 50% (by weight) of the cellulose ether.
The acrylic resin is preferably a methacylate such as methacrylic acid copolymer USNF Type A (Eudragit L, Trade Mark), Type B (Eudragit S, Trade Mark), Type C (Eudragit L 100-55, Trade Mark), Eudragit NE 30D, Eudragit E, Eudragit RL and Eudragit RS. Preferably the matrix contains between 0.5 and 60% by weight, preferably between 1% and 50% by weight of the acrylic resin.
In the absence of polyalkylene glycol, the matrix preferably contains between 1% and 40%, especially between 2% and 36% (by weight) of the aliphatic alcohol When polyalkylene glycol is present in the oral dosage form, then the combined weight of the aliphatic alcohol and the polyalkylene glycol preferably constitutes between 2% and 40%, especially between 2 and 36% (by weight) of the matrix.
The polyalkylene glycol may be, for example, polypropylene glycol or, which is preferred, polyethylene glycol. The number average molecular weight of the at least one polyalkylene glycol is preferably between 200 and 15000 especially between 400 and 12000.
The morphine-containing controlled release matrix can readily be prepared by dispersing the active ingredient in the controlled release system using conventional pharmaceutical techniques such as melt granulation, wet granulation, dry blending, dry granulation or coprecipitation.
Another form of sustained release formulation comprises spheroids obtained by spheronizing the morphine (or salt thereof) with a spheronizing agent such as microcrystalline cellulose.
In order that the invention may be well understood the following examples are given by way of illustration only.
EXAMPLES Pellets, having the formulations given in Table I below, were prepared by the steps of: (i) placing the ingredients, in a total amount by weight of 10 kg, in the bowl of a 70 litre capacity. Collette Gral mixer (or equivalent), equipped with variable speed mixing and granulating blades; (ii) mixing the ingredients while applying heat until the contents of the bowl are pelletised; (iii) discharging the pellets from the mixer and sieving them to separate out the pellets collected between 0.5 and 2 mm aperture sieves.
Table I Example No. 1 2 3 4 5 6 7 8 Morphine Sulphate 15 15 15 23 55 55 55 55 (wt.%) Hydrogenated castor oil U.S.N.F. (wt.%) 77 76 75 70 - - - Hydrogenated vegetable oil U.S.N.F. (wt.%) - - - - 42.8 45 44.95 42.0 Polyethylene glycol 6000 U.S.N.F. (wt.%) 8 9 10 7 0.2 - 0.05 Dicalcium phosphate anhydrous USP (wt.6) - - - - 2 - - 3 The in vitro release rates of the products of Examples 1, 2, 3 and 5 were assessed by the modified Ph.Eur. Basket method as noted above. For each of the products, six samples of the pellets, each sample containing a total of 30 mg of morphine sulphate, were tested. The results set out in Table II below give the mean values for each of the six samples tested.
TABLE II Hours Product of Example after start of test 1 2 3 5 (% morphine released) 2 19 25 33 44 4 27 36 49 57 6 34 45 62 66 8 41 52 72 72 12 53 64 86 81 18 66 77 96 89 24 76 86 101 92 Pharmacokinetic studies in healthy human volunteers have indicated peak plasma levels of from 2.5 to 21.6 ng/ml of morphine at times between 1.0 and 3.5 hours following administration of a single capsule containing pellets of Examples 1,2, 3 or 5 in an amount sufficient to provide a morphine sulphate dose of 30 mg.

Claims (7)

CLAIMS:
1. An orally administrable sustained release dosage unit form containing morphine, or a pharmaceutically salt thereof, as active ingredient, which composition gives a peak plasma level at 1.0 to 3.5 hours after administration.
2. A pharmaceutical composition as claimed in claim 1 containing from 10 to 500 mg of morphine (calculated as morphine sulphate).
3. A pharmaceutical composition as claimed in claim 1 or claim 2 having in vitro release characteristics such that the formulation (when assessed by the modified Ph.Eur. Basket Method at 100 rpm in 900 ml aqueous buffer, pH 6.5, at 370C), releases from 15 to 50% of active ingredient two hours after start of test, 20 to 65% at 4 hours after start of test; 25 to 75 at 6 hours after start of test; 40 to 90% at 12 hours after start of test, from 55 to 100% at 18 hours after start test and 65 to 100% at 24 hours after start of test.
4. A pharmaceutical composition as claimed in any one of the preceding claims comprising a capsule filled with pellets essentially comprising the active ingredient and a hydrophobic release control material.
5. A pharmaceutical composition as claimed in claim 4 which has been prepared by a melt pelletisation process.
6. A pharmaceutical composition as claimed in claim 4 or claim 5 also containing from 00.1 to 20% by weight, based on the total weight of the pellets, of a release control component comprising a water-soluble fusible material or a particulate soluble or insoluble organic or inorganic material.
7. A pharmaceutical composition as claimed in claim 1 substantially as hereinbefore described with reference to the Examples.
GB9315467A 1991-12-24 1993-07-27 Sustained release morphine compositions Withdrawn GB2281204A (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
GB9315467A GB2281204A (en) 1993-07-27 1993-07-27 Sustained release morphine compositions
IL10994494A IL109944A (en) 1993-07-01 1994-06-08 Sustained release dosage unit forms containing morphine and a method of preparing these sustained release dosage unit forms
ES94304144T ES2124372T5 (en) 1993-07-01 1994-06-09 SUSTAINED RELEASE COMPOSITIONS CONTAINING MORPHINE.
SG1996009186A SG50706A1 (en) 1993-07-01 1994-06-09 Sustained release compositions and a method of preparing pharmaceutical compositions
EP94304144A EP0636370B2 (en) 1993-07-01 1994-06-09 Sustained release compositions containing morphine
AT94304144T ATE172376T1 (en) 1993-07-01 1994-06-09 MORPHINE-CONTAINING MEDICINAL COMPOSITIONS WITH DELAYED RELEASE
DK94304144T DK0636370T4 (en) 1993-07-01 1994-06-09 Deposits containing morphine
DE69414046T DE69414046T3 (en) 1993-07-01 1994-06-09 Morphine-containing medicinal compositions with delayed drug delivery
CZ19941550A CZ287918B6 (en) 1993-07-01 1994-06-23 Orally administered unit dosage form with controlled release and process for preparing thereof
SK763-94A SK280534B6 (en) 1993-07-01 1994-06-23 Sustained release preparations of morphine and a method of preparing the same
NZ260883A NZ260883A (en) 1993-07-01 1994-06-29 Oral sustained-release medicaments containing morphine
IN571MA1994 IN183742B (en) 1993-07-27 1994-06-29
PL94304062A PL179282B1 (en) 1993-07-01 1994-06-30 Retarded release compositions and method of obtaining such compositions
FI943141A FI114285B (en) 1993-07-01 1994-06-30 Process for preparing sustained release pharmaceutical dosage unit form
CA002127166A CA2127166C (en) 1993-07-01 1994-06-30 Sustained release morphine compositions and a method of preparation
AU66105/94A AU6610594A (en) 1991-12-24 1994-06-30 Sustained release compositions and a method of preparing pharmaceutical compositions
NO942470A NO306449B1 (en) 1993-07-01 1994-06-30 Orally administered morphine preparation for sustained release as well as preparation of multiparticulates for use in the preparation
HU9402007A HU220075B (en) 1993-07-01 1994-07-01 Retarde pharmaceutical compositions containing morphine and process for producing them
KR1019940015740A KR100365572B1 (en) 1993-07-01 1994-07-01 Sustained-release and pharmaceutical compositions
JP15121994A JP3647897B2 (en) 1993-07-01 1994-07-01 Sustained release unit dosage form
US08/843,571 US5879705A (en) 1993-07-27 1997-04-18 Sustained release compositions of morphine and a method of preparing pharmaceutical compositions
AU52995/98A AU722358B2 (en) 1991-12-24 1998-02-06 Sustained release compositions and a method of preparing pharmaceutical compositions
US09/264,399 US6143328A (en) 1993-07-27 1999-03-08 Sustained release compositions and a method of preparing pharmaceutical compositions

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB9315467A GB2281204A (en) 1993-07-27 1993-07-27 Sustained release morphine compositions

Publications (2)

Publication Number Publication Date
GB9315467D0 GB9315467D0 (en) 1993-09-08
GB2281204A true GB2281204A (en) 1995-03-01

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Application Number Title Priority Date Filing Date
GB9315467A Withdrawn GB2281204A (en) 1991-12-24 1993-07-27 Sustained release morphine compositions

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GB (1) GB2281204A (en)
IN (1) IN183742B (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2284760B (en) * 1993-11-23 1998-06-24 Euro Celtique Sa A method of preparing pharmaceutical compositions by melt pelletisation
US5843480A (en) 1994-03-14 1998-12-01 Euro-Celtique, S.A. Controlled release diamorphine formulation
US5849240A (en) 1993-11-23 1998-12-15 Euro-Celtique, S.A. Method of preparing sustained release pharmaceutical compositions
US5891471A (en) 1993-11-23 1999-04-06 Euro-Celtique, S.A. Pharmaceutical multiparticulates
US5958452A (en) 1994-11-04 1999-09-28 Euro-Celtique, S.A. Extruded orally administrable opioid formulations
US6068855A (en) 1994-11-03 2000-05-30 Euro-Celtique S. A. Pharmaceutical composition containing a fusible carrier and method for producing the same
WO2004045551A2 (en) * 2002-11-15 2004-06-03 Branded Products For The Future Pharmaceutical composition
US8557286B1 (en) 1999-04-22 2013-10-15 Euroceltique, S.A. Method for producing a water-insoluble amorphous or partially amorphous controlled release matrix

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3634584A (en) * 1969-02-13 1972-01-11 American Home Prod Sustained action dosage form
EP0108218A2 (en) * 1982-10-08 1984-05-16 Verex Laboratories, Inc. Constant release rate solid oral dosage formulation of pharmaceutical compounds having a high degree of water solubility
EP0271193A2 (en) * 1986-10-31 1988-06-15 Euroceltique S.A. Controlled release hydromorphone composition
EP0377518A2 (en) * 1989-01-06 1990-07-11 F.H. FAULDING & CO. LIMITED Sustained release pharmaceutical composition
WO1992001446A1 (en) * 1990-07-20 1992-02-06 Aps Research Limited Sustained-release formulations
WO1992002209A1 (en) * 1990-07-31 1992-02-20 Aiache Jean Marc Method for preparing a bioadhesive galenical and galenical thereby obtained

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3634584A (en) * 1969-02-13 1972-01-11 American Home Prod Sustained action dosage form
EP0108218A2 (en) * 1982-10-08 1984-05-16 Verex Laboratories, Inc. Constant release rate solid oral dosage formulation of pharmaceutical compounds having a high degree of water solubility
EP0271193A2 (en) * 1986-10-31 1988-06-15 Euroceltique S.A. Controlled release hydromorphone composition
EP0377518A2 (en) * 1989-01-06 1990-07-11 F.H. FAULDING & CO. LIMITED Sustained release pharmaceutical composition
WO1992001446A1 (en) * 1990-07-20 1992-02-06 Aps Research Limited Sustained-release formulations
WO1992002209A1 (en) * 1990-07-31 1992-02-20 Aiache Jean Marc Method for preparing a bioadhesive galenical and galenical thereby obtained

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
British National Formulary No.25 (March 1993) page 181-see MST Continus *
Curr.Ther.Res.47 pages 869-878 (1990) *

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5849240A (en) 1993-11-23 1998-12-15 Euro-Celtique, S.A. Method of preparing sustained release pharmaceutical compositions
US5891471A (en) 1993-11-23 1999-04-06 Euro-Celtique, S.A. Pharmaceutical multiparticulates
GB2284760B (en) * 1993-11-23 1998-06-24 Euro Celtique Sa A method of preparing pharmaceutical compositions by melt pelletisation
US6162467A (en) 1993-11-23 2000-12-19 Euro-Celtique, S.A. Sustained release compositions and a method of preparing pharmaceutical compositions
US5965163A (en) 1993-11-23 1999-10-12 Euro-Celtique, S.A. Substained release compositions and a method of preparing pharmaceutical compositions
US5843480A (en) 1994-03-14 1998-12-01 Euro-Celtique, S.A. Controlled release diamorphine formulation
US6068855A (en) 1994-11-03 2000-05-30 Euro-Celtique S. A. Pharmaceutical composition containing a fusible carrier and method for producing the same
US6335033B2 (en) 1994-11-04 2002-01-01 Euro-Celtique, S.A. Melt-extrusion multiparticulates
US5965161A (en) 1994-11-04 1999-10-12 Euro-Celtique, S.A. Extruded multi-particulates
US6261599B1 (en) 1994-11-04 2001-07-17 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US5958452A (en) 1994-11-04 1999-09-28 Euro-Celtique, S.A. Extruded orally administrable opioid formulations
US6706281B2 (en) 1994-11-04 2004-03-16 Euro-Celtique, S.A. Melt-extrusion multiparticulates
US6743442B2 (en) 1994-11-04 2004-06-01 Euro-Celtique, S.A. Melt-extruded orally administrable opioid formulations
US8557286B1 (en) 1999-04-22 2013-10-15 Euroceltique, S.A. Method for producing a water-insoluble amorphous or partially amorphous controlled release matrix
WO2004045551A2 (en) * 2002-11-15 2004-06-03 Branded Products For The Future Pharmaceutical composition
WO2004045551A3 (en) * 2002-11-15 2004-12-09 Branded Products For The Futur Pharmaceutical composition
US7192966B2 (en) 2002-11-15 2007-03-20 Branded Products For The Future Pharmaceutical composition
US7652026B2 (en) 2002-11-15 2010-01-26 Branded Products For The Future Pharmaceutical composition
US7973048B2 (en) 2002-11-15 2011-07-05 Branded Products For The Future Pharmaceutical composition
US8188108B2 (en) 2002-11-15 2012-05-29 Branded Products For The Future Pharmaceutical composition

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