EP1033977A2 - Compositions pharmaceutiques ayant la forme de poudres de polymeres reticules charges de medicaments et procede de preparation correspondant au moyen de fluides supercritiques - Google Patents

Compositions pharmaceutiques ayant la forme de poudres de polymeres reticules charges de medicaments et procede de preparation correspondant au moyen de fluides supercritiques

Info

Publication number
EP1033977A2
EP1033977A2 EP98965674A EP98965674A EP1033977A2 EP 1033977 A2 EP1033977 A2 EP 1033977A2 EP 98965674 A EP98965674 A EP 98965674A EP 98965674 A EP98965674 A EP 98965674A EP 1033977 A2 EP1033977 A2 EP 1033977A2
Authority
EP
European Patent Office
Prior art keywords
cross
linked
drug
supercritical fluid
compositions
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Withdrawn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
EP98965674A
Other languages
German (de)
English (en)
Inventor
Fabio Carli
Italo Colombo
Paolo Alessi
Ireneo Kikic
Angelo Cortesi
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.)
Adare Pharmaceuticals SRL
Original Assignee
Eurand International SpA
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 Eurand International SpA filed Critical Eurand International SpA
Publication of EP1033977A2 publication Critical patent/EP1033977A2/fr
Withdrawn legal-status Critical Current

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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • 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
    • 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
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Definitions

  • the present invention refers to pharmaceutical compositions in powder form consisting of active substances loaded on cross-linked polymers prepared with the technology of the supercritical fluids.
  • the properties of the supercritical fluids may be exploited in the processing of the materials allowing, for example, the production of powders having controlled granulometry (J. W. Tom, P. G. Debenedetti, J. Aerosol. Sci., 22, 555, 1991 ).
  • the present invention refers to pharmaceutical compositions in powder form prepared by loading drugs solubilized in supercritical fluids on cross-linked polymers.
  • compositions are prepared by: 1 ) solubilization of the drug in a supercritical fluid; 2 ⁇ contacting the supercritical fluid containing the solubilized drug with the cross- linked polymer;
  • the fluid consisting of a pure component or mixture, by a pump is taken to the desired pressure conditions. It is sent to a first container and from this one it is passed through a heat exchanger in order to take it to temperature and pressure conditions higher than those at which it can be considered as supercritical.
  • carbon dioxide CO 2
  • ethylene higher than 9°C and 54.4 bar
  • carbon dioxide (CO 2 ) mixed with methanol (7%) it is taken to conditions above 40°C and 80 bar.
  • the supercritical fluid is then passed through an extractor containing the drug.
  • the supercritical fluid stream consisting of a pure component or mixture, containing certain amount of drug which solubilized at the temperature and pressure conditions fixed in advance, is contacted in a reactor practically set to the same operative conditions, with the polymer, according to a static or a dynamic process.
  • a predeterminate volume of the supercritical fluid with the solubilized drug is introduced in an adequate container and left to equilibrate with an adequate quantity of polymer, for a contact time in the range between 5 minutes and 72 hours, preferably between 0.25 hours and 24 hours; this equilibration loading step can be repeated if necessary more times.
  • the stream of the supercritical fluid generated by the pump, at the outlet of the extractor is passed through a column, of predetermined size and length, containing the polymer, for a contact time between 5 minutes and 72 hours, preferably between 0.25 hours and 24 hours.
  • Said process embodiments, static and dynamic can be combined; for example after passing dynamically a given volume of supercritical fluid with the solubilized drug through a column of predetermined sizes, the stream is stopped, the supercritical fluid is left in static contact with the polymer for a predetermined time and subsequently the stream of the supercritical fluid is passed again through the column.
  • the loading of the drug occurs essentially through the effect of the partitioning of the drug itself between the supercritical fluid and the polymer.
  • This stage of the operation may be if necessary aided by acting on other factors assisting the release of the drug from the supercritical fluid.
  • the fluid stream is passed through an absorber containing activated carbon or other material suitable to remove from the stream itself any trace of the, in case residual, drug.
  • the fluid stream may then be brought back to the ambient conditions and drained or if necessary cooled, sent to a reflux receiver and from this one by the pump to the extractor.
  • the polymers according to the present invention are cross-linked hydrophilic and hydrophobic polymers.
  • cross-linked polymers we can mention, as an however not exhaustive exemplification: the cross-linked polyvinyl pyrrolidone, the cross-linked sodium carboxymethyl cellulose and cross-linked sodium starch glycolate, among the hydrophilic ones; the cross-linked polystyrene, the cross- linked acrylic acid and the sodium salt of cross-linked polymethyl methacrylate among the hydrophobic ones.
  • Analgesics and non steroidal antiinflammatories and their salts sodium diclofenac, ibuprofen, naproxen, etc.; antibactericals: amoxicillin, cephalosporins, etc.; antifungals and antipsoriatics: ketoconazole, griseofulvin, itraconazole, thioconazole, etc.; antivirals: acyclovir, gancyclovir, etc.; antineoplastics and immunosuppressives: ciclosporin, etoposide, taxole and derivatives, etc.; anxiolytics, sedatives, hypnotics: lorazepam, oxazepam, temazepam, etc.; sexual hormones: medroxyprogesterone acetate, testosterone, estradiol, progesterone, etc.; peptidic molecules having different activity: LH-RH analogues, calcitonins, glutathione.;
  • compositions according to the present invention contain from 0.1 to 99.9% and preferably from 0.1 to 50% by weight of the active principle with respect to the polymer.
  • the compositions are formulated as packets or as tables, perles pellets or granules for pharmaceutical use.
  • Examples No. 3-6 15 grams of polymeric materials (respectively physically cross-linked polyvinyl pyrrolidone, chemically cross-linked polyvinyl pyrrolidone, cross-linked sodium starch glycolate and acrylic acid cross-linked with allilic esters of sucrose) are put into a 200 ml reactor and contacted with CO2 saturated with the drug.
  • the reactor is washed first with CO2 and then a stream of CO2 saturated with different drugs (nimesulide, ketoprofen, piroxicam, cimetidine respectively) is introduced at 160 bar and 60 °C.
  • drugs nimesulide, ketoprofen, piroxicam, cimetidine respectively
  • the concentrations of drug in the polymers are 22.2; 25.6; 15.3; and 20.4% respectively.

Landscapes

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

Abstract

On prépare des compositions pharmaceutiques sous forme de poudres, en chargeant sur des polymères réticulés des médicaments mis en solution dans des fluides supercritiques. Ce procédé de chargement est réalisé en deux étapes. Dans la première étape, le fluide supercritique est saturé avec le médicament dans des conditions de température et de pression appropriées. Dans la seconde étape, le fluide supercritique contenant le médicament est mis en contact avec le polymère réticulé. Grâce à ses propriétés particulières, le fluide supercritique pénètre dans le polymère et permet au médicament d'imprégner le polymère. Après le retrait du fluide, le médicament reste dans le polymère.
EP98965674A 1997-11-19 1998-11-16 Compositions pharmaceutiques ayant la forme de poudres de polymeres reticules charges de medicaments et procede de preparation correspondant au moyen de fluides supercritiques Withdrawn EP1033977A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ITMI972571 1997-11-19
IT97MI002571A IT1296464B1 (it) 1997-11-19 1997-11-19 Composizioni farmaceutiche in forma di polveri di polimeri reticolati caricati con farmaci e relativo processo di preparazione mediante
PCT/EP1998/007311 WO1999025322A2 (fr) 1997-11-19 1998-11-16 Compositions pharmaceutiques ayant la forme de poudres de polymeres reticules charges de medicaments et procede de preparation correspondant au moyen de fluides supercritiques

Publications (1)

Publication Number Publication Date
EP1033977A2 true EP1033977A2 (fr) 2000-09-13

Family

ID=11378230

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98965674A Withdrawn EP1033977A2 (fr) 1997-11-19 1998-11-16 Compositions pharmaceutiques ayant la forme de poudres de polymeres reticules charges de medicaments et procede de preparation correspondant au moyen de fluides supercritiques

Country Status (9)

Country Link
EP (1) EP1033977A2 (fr)
JP (1) JP2001522873A (fr)
KR (1) KR20010032251A (fr)
AU (1) AU738748B2 (fr)
BR (1) BR9814656A (fr)
CA (1) CA2310423A1 (fr)
IT (1) IT1296464B1 (fr)
NZ (1) NZ505290A (fr)
WO (1) WO1999025322A2 (fr)

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Publication number Priority date Publication date Assignee Title
GB9920558D0 (en) * 1999-08-31 1999-11-03 Bradford Particle Design Ltd Methods for particle formation and their products
AU2001240515A1 (en) * 2000-01-17 2001-07-31 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Method for modifying the surfaces of fine-porous adsorbents
IT1318404B1 (it) * 2000-03-17 2003-08-25 Eurand Int Processo per la preparazione di formulazioni a rilascio accelerato conimpiego di fluidi compressi.
EP1258241A1 (fr) * 2001-05-16 2002-11-20 BIOPROGRESS S.p.A. Procédé permettant d'accroitre la biodisponibilité de nimesulide
CN1255099C (zh) 2001-05-30 2006-05-10 South African Scientific and Industrial Research Center 包封活性物质的方法
US20030044514A1 (en) * 2001-06-13 2003-03-06 Richard Robert E. Using supercritical fluids to infuse therapeutic on a medical device
DE10132366A1 (de) * 2001-07-04 2003-01-30 Degussa Verfahren zur physikalischen Behandlung von Stärke(-Derivaten)
FR2830760B1 (fr) 2001-10-12 2004-06-04 Pf Medicament Procede de preparation d'un compose d'interaction de substances actives avec un support poreux par fluide supercritique
GB0127786D0 (en) * 2001-11-20 2002-01-09 Univ Nottingham Impregnation of antimicrobial substances
DK1515699T3 (da) * 2002-03-07 2009-05-04 Eurand Pharmaceuticals Ltd Fremgangsmåde til ladning og termodynamisk aktivering af lægemidler på polymerer ved hjælp af superkritiske fluida
KR100508518B1 (ko) * 2002-11-13 2005-08-17 한미약품 주식회사 초임계유체 공정을 이용한 파클리탁셀 고체분산체의 제조방법 및 이 방법으로 제조된 파클리탁셀 고체분산체
FR2854079B1 (fr) 2003-04-25 2007-11-30 Pf Medicament Procede de preparation de complexes moleculaires
US7507823B2 (en) 2004-05-06 2009-03-24 Bristol-Myers Squibb Company Process of making aripiprazole particles
EP1611877A1 (fr) 2004-06-28 2006-01-04 Universidade de Coimbra Méthodes pour la préparation d'articles ophthalmiques thérapeutiques à la libération prolongée en utilisant des fluides compressés pour l'imprégnation des medicaments
GB2417900A (en) * 2004-09-11 2006-03-15 Medway Science Technologies Lt Composition for oral drug delivery
KR101374928B1 (ko) * 2005-11-09 2014-03-14 노파르티스 아게 일시적 가소제를 사용한 약학 조성물의 제조 방법
GB0812742D0 (en) 2008-07-11 2008-08-20 Critical Pharmaceuticals Ltd Process
FR2945449B1 (fr) * 2009-05-15 2012-10-05 Pf Medicament Procede d'impregnation par co2 supercritique
CN105687141A (zh) * 2016-03-04 2016-06-22 中国药科大学 超临界抗溶剂法制备尼美舒利-左旋聚乳酸(Nim-PLLA)复合微球的工艺研究
CN112812355B (zh) * 2020-12-31 2022-09-23 厦门天生爱科技有限公司 一种具有缓释挥发性中草药有效成分的功能高分子发泡材料、制备方法和用途
CN113425895A (zh) * 2021-07-12 2021-09-24 大连大学 一种载药骨修复内固定材料及其制备方法

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IE63321B1 (en) * 1986-02-03 1995-04-05 Elan Corp Plc Drug delivery system
FR2635043B1 (fr) * 1988-08-05 1990-09-28 Michelin & Cie Appareil de fabrication d'un renforcement pour pneumatiques, ledit renforcement etant constitue a partir d'un seul fil
CH677876A5 (en) * 1988-10-21 1991-07-15 Siegfried Ag Prepn. of coronary active 1,4-di:hydro-pyridine(s) in sorbed form - by pptn. on and/or in polyacrylate particles to improve bio-availability
IT1252867B (it) * 1991-12-31 1995-06-28 Gentili Ist Spa Composizioni farmaceutiche contenenti progesterone ad elevata biodisponibilita'
DE4202320A1 (de) * 1992-01-29 1993-08-05 Dierk Dr Knittel Verfahren zum impraegnieren von substraten
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Also Published As

Publication number Publication date
CA2310423A1 (fr) 1999-05-27
WO1999025322A3 (fr) 1999-08-19
AU2153199A (en) 1999-06-07
NZ505290A (en) 2002-08-28
BR9814656A (pt) 2000-10-03
KR20010032251A (ko) 2001-04-16
ITMI972571A1 (it) 1999-05-19
JP2001522873A (ja) 2001-11-20
WO1999025322A2 (fr) 1999-05-27
AU738748B2 (en) 2001-09-27
IT1296464B1 (it) 1999-06-25

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