WO1999025322A2 - Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids - Google Patents

Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids Download PDF

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Publication number
WO1999025322A2
WO1999025322A2 PCT/EP1998/007311 EP9807311W WO9925322A2 WO 1999025322 A2 WO1999025322 A2 WO 1999025322A2 EP 9807311 W EP9807311 W EP 9807311W WO 9925322 A2 WO9925322 A2 WO 9925322A2
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WO
WIPO (PCT)
Prior art keywords
cross
linked
drug
supercritical fluid
compositions
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Application number
PCT/EP1998/007311
Other languages
French (fr)
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WO1999025322A3 (en
Inventor
Fabio Carli
Italo Colombo
Paolo Alessi
Ireneo Kikic
Angelo Cortesi
Original Assignee
Eurand International S.P.A.
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 S.P.A. filed Critical Eurand International S.P.A.
Priority to AU21531/99A priority Critical patent/AU738748B2/en
Priority to JP2000520756A priority patent/JP2001522873A/en
Priority to EP98965674A priority patent/EP1033977A2/en
Priority to CA002310423A priority patent/CA2310423A1/en
Priority to NZ505290A priority patent/NZ505290A/en
Priority to BR9814656-4A priority patent/BR9814656A/en
Priority to KR1020007005454A priority patent/KR20010032251A/en
Publication of WO1999025322A2 publication Critical patent/WO1999025322A2/en
Publication of WO1999025322A3 publication Critical patent/WO1999025322A3/en

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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.
  • 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.;
  • 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.

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  • 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

Pharmaceutical compositions in powder form are prepared by loading drugs solubilized in supercritical fluids on cross-linked polymers. The loading process is carried out by means of two steps. In the first step the supercritical fluid is saturated with the drug in suitable temperature and pressure conditions. In the second step the supercritical fluid containing the drug is contacted with the cross-linked polymer. Owing to its particular properties the supercritical fluid penetrates into the polymer and allows the drug to impregnate the polymer itself. After the removal of the fluid the drug remains in the polymer itself.

Description

PHARMACEUTICAL COMPOSITIONS HAVING THE SHAPE OF POWDERS OF CROSS-LINKED POLYMERS LOADED WITH DRUGS AND RELATED PREPARATION PROCESS BY SUPERCRITICAL FLUIDS FIELD OF THE INVENTION 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. PRIOR ART
The technology with supercritical fluids (V. Krukonis, Proc. Ill International Symposium on Supercritical Fluids, Strasbourg, Vol. 1 ,1 , 1994; Proceedings IV International Symposium on Supercritical Fluids, Sendai (Japan), May, 11-14, 1997, S. Sato and K. Arai Eds.) is notably developing owing to the particular properties of these fluids which allow a safer use of them instead of the normal organic solvents even in the pharmaceutical field (K. A. Larson, M. L. King, Biotechnol. Prog., 3, 73, 1986) in the operations of extraction and purification (G. Brunner, "Gas Extraction", Springer, Darmstadt, 1994).
Besides for these applications 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 ).
Among the processed materials a particular attention has been devoted to the polymeric materials, both for the production of micronized powders and for their fractionation (M. McHugh, V. Krukonis, "Supercritical Fluid Extraction", Butterworth, Meinemann, 1994). Another particularly interesting aspect consists of the utilization of the technology with supercritical fluids for the loading of essentially linear polymers, with additives (C. A. Perman et al., US Patent 5,508,060; M. L. Sand, US Patent 4,598,006). In particular the importance of the absence of cross-linking in the polymer is pointed out (M. L. Sand, US Patent 4,598,006) in order to allow the operation of impregnation. Unexpectedly, using cross-linked polymers we succeeded to load them, reaching reasonable loading levels, with drugs, in presence of supercritical fluids. SUMMARY The present invention refers to pharmaceutical compositions in powder form prepared by loading drugs solubilized in supercritical fluids on cross-linked polymers.
Said 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;
3) impregnation of the cross-linked polymer with the supercritical fluid containing the drug;
4) removal of the supercritical fluid with consequent loading of the drug in the cross-linked polymer itself.
DETAILED DESCRIPTION OF THE INVENTION
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. For example, in the case of pure components, carbon dioxide (CO2) is taken to conditions higher than 31 °C and 73.8 bar; ethylene higher than 9°C and 54.4 bar; methane higher than -82°C and 46.0 bar; propylene higher than 92°C and 46.2 bar; nitrous oxide (N2O) higher than 36.4°C and 72.45 bar , in the case of a mixture of carbon dioxide (CO2) 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. At the outlet of the extractor 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. In the static case 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. In the case of the dynamic process 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. In both the processes 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. At the outlet from the impregnation reactor 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. Among the 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.
Among the drugs which may be formulated according to the invention we may mention, as an however not exhaustive exemplification:
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.
The 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
For the illustrative aim of the invention the following examples are reported hereinafter: Example No. 1
5 grams of polymer, cross-linked polyvinyl pyrrolidone, placed in a column of 50 cm length and 0.6 cm size, are contacted with CO2 saturated with nimesulide at
160 bar and 60 C°. The flux of the incoming stream of saturated CO2 expressed in flow of liquid CO2 is equal to 0.1 litres/minute. At the end of the test, after 8 hours, the polymer turns out to be impregnated of nimesulide for an amount equal to
24.47%.
Example No. 2
5 grams of polymer, cross-linked polymethyl methacrylate, placed in a column of
50 cm length and 0.6 cm size, are contacted with CO2 saturated with acyclovir at 220 bar and 50 C°: the flux of the incoming stream of saturated CO2 expressed in flow of liquid CO2 is equal to 0.1 litres/minute.
At the end of the test, after 24 hours, the polymer turns out to be impregnated of acyclovir for an amount equal to 21.2%.
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.
At the end of the tests, after contact times respectively of 0.5 hour, 0.25 hour, 1 hour, 2 hours, the concentrations of drug in the polymers are 22.2; 25.6; 15.3; and 20.4% respectively.

Claims

1. Pharmaceutical compositions in form of powders consisting of cross-linked polymers loaded with active principles by an impregnation process with supercritical fluids.
2. Compositions as claimed in claim 1 , characterized in that said active principles are present in the powders of the cross-linked polymers in an amount ranging from 0.1 to 99.9% by weight, preferably in an amount from 0.1 to 50% by weight with respect to the polymers.
3. Compositions as claimed in claim 1 , characterized in that said cross-linked polymers comprise hydrophilic cross-linked polymers such as the cross-linked polyvinyl pyrrolidone, the cross-linked sodium starch glycolate, the cross-linked sodium carboxymethyl cellulose.
4. Compositions as claimed in claim 1 , characterized in that said cross-linked polymers comprise hydrophobic cross-linked polymers such as the cross-linked polystirene, the cross-linked acrylic acid or the cross-linked polymethyl methacrylate sodium salt.
5. Compositions as claimed in claim 1 , characterized in that said powders are formulated as packets or as tablets, perles, pellets or granules for pharmaceutical use.
6. Process for the preparation of pharmaceutical compositions as defined in claim 1 , characterized by: 1) solubilization of the drug in a supercritical fluid; 2) contacting the supercritical fluid containing the solubilized drug with the cross- linked polymer; 3) impregnation of the cross-linked polymer with the supercritical fluid containing the drug; 4) removal of the supercritical fluid with consequent loading of the drug in the cross-linked polymer itself.
7. Process as claimed in claim 6, characterized in that said contacting step is carried out by a static or a dynamic embodiment.
8. Process as claimed in claim 6, characterized in that said contacting step is carried out by a contact time from 5 minutes to 72 hours.
9. Process as claimed in claim 6, characterized in that said contacting step is carried out by a contact time from 0.25 hours to 24 hours.
PCT/EP1998/007311 1997-11-19 1998-11-16 Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids WO1999025322A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU21531/99A AU738748B2 (en) 1997-11-19 1998-11-16 Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids
JP2000520756A JP2001522873A (en) 1997-11-19 1998-11-16 Pharmaceutical compositions having crosslinked polymers in powder form bearing pharmaceuticals and related supercritical fluid preparation methods
EP98965674A EP1033977A2 (en) 1997-11-19 1998-11-16 Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids
CA002310423A CA2310423A1 (en) 1997-11-19 1998-11-16 Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids
NZ505290A NZ505290A (en) 1997-11-19 1998-11-16 Pharmaceutical compositions comprising cross-linked polymers loaded with drugs prepared by using supercritical fluids to solubilize and load the drugs on to the polymers
BR9814656-4A BR9814656A (en) 1997-11-19 1998-11-16 Pharmaceutical compositions in the form of powders, and process for the preparation of pharmaceutical compositions
KR1020007005454A KR20010032251A (en) 1997-11-19 1998-11-16 Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT97MI002571A IT1296464B1 (en) 1997-11-19 1997-11-19 PHARMACEUTICAL COMPOSITIONS IN THE FORM OF DRUG-LOADED CROSS-LINKED POLYMER POWDERS AND RELATED PREPARATION PROCESS BY MEANS
ITMI97A002571 1997-11-19

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WO1999025322A2 true WO1999025322A2 (en) 1999-05-27
WO1999025322A3 WO1999025322A3 (en) 1999-08-19

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

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001015664A2 (en) * 1999-08-31 2001-03-08 Bradford Particle Design Limited Coformulation methods and their products
WO2001052981A1 (en) * 2000-01-17 2001-07-26 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for modifying the surfaces of fine-porous adsorbents
WO2001068054A1 (en) * 2000-03-17 2001-09-20 Eurand International S.P.A. Process for the preparation of accelerated release formulations using compressed fluids
EP1258241A1 (en) * 2001-05-16 2002-11-20 BIOPROGRESS S.p.A. Method of increasing the bioavailability of nimesulide
FR2825292A1 (en) * 2001-05-30 2002-12-06 Csir New process for coating an active substance with an inter polymeric complex in a supercritical liquid
WO2002100456A1 (en) * 2001-06-13 2002-12-19 Boston Scientific Limited Using supercritical fluids to infuse therapeutic on a medical device
WO2003045448A1 (en) * 2001-11-20 2003-06-05 The University Of Nottingham Impregnation of polymeric substrates with antimicrobial substances using superficial fluids
WO2003074028A1 (en) * 2002-03-07 2003-09-12 Eurand Pharmaceuticals Ltd. Process for loading and thermodynamically activating drugs on polymers by means of supercritical fluids
JP2004535495A (en) * 2001-07-04 2004-11-25 デグサ アクチエンゲゼルシャフト Physical treatment of starch (-derivative)
EP1611877A1 (en) 2004-06-28 2006-01-04 Universidade de Coimbra Method for preparing sustained-release therapeutic ophthalmic articles using compressed fluids for impregnation of drugs
GB2417900A (en) * 2004-09-11 2006-03-15 Medway Science Technologies Lt Composition for oral drug delivery
US7390411B2 (en) 2001-10-12 2008-06-24 Pierre Fabre Medicament Method for preparing a compound of interaction of active substances with a porous support using supercritical fluid
US7507823B2 (en) 2004-05-06 2009-03-24 Bristol-Myers Squibb Company Process of making aripiprazole particles
FR2945449A1 (en) * 2009-05-15 2010-11-19 Pf Medicament SUPERCRITICAL CO2 IMPREGNATION PROCESS
EP2289561A1 (en) 2003-04-25 2011-03-02 Pierre Fabre Médicament Method for preparing molecular complexes
US9226900B2 (en) 2008-07-11 2016-01-05 Critical Pharmaceuticals Limited Process for preparing microparticles
CN105687141A (en) * 2016-03-04 2016-06-22 中国药科大学 Technical study for preparing Nim-PLLA (nimesulide-poly-l-lactic acid) composite microsphere with supercritical anti-solvent method
CN112812355A (en) * 2020-12-31 2021-05-18 厦门天生爱科技有限公司 Functional polymer foaming material with slow-release volatile Chinese herbal medicine effective components, preparation method and application
CN113425895A (en) * 2021-07-12 2021-09-24 大连大学 Drug-loaded bone repair internal fixation material and preparation method thereof

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KR100508518B1 (en) * 2002-11-13 2005-08-17 한미약품 주식회사 Method for the preparation of paclitaxel solid dispersion by using the supercritical fluid process and paclitaxel solid dispersion prepared thereby
KR101374928B1 (en) * 2005-11-09 2014-03-14 노파르티스 아게 Process for making pharmaceutical compositions with a transient plasticizer

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US5039372A (en) * 1988-08-05 1991-08-13 Compagnie Generale Des Etablissements Michelin - Michelin Et Cie Component elements of an apparatus for the manufacture of a tire reinforcement
US5128142A (en) * 1986-02-03 1992-07-07 Elan Corporation, Plc Sustained release drug delivery system
WO1993012797A1 (en) * 1991-12-31 1993-07-08 Istituto Gentili S.P.A. Pharmaceutical compositions containing natural progesterone having a high biological availability
DE4202320A1 (en) * 1992-01-29 1993-08-05 Dierk Dr Knittel Impregnating substrate by contact with supercritical fluid contg. impregnant - followed by conversion of fluid to subcritical state
WO1994018264A1 (en) * 1993-02-11 1994-08-18 Minnesota Mining And Manufacturing Company Methods of polymer impregnation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5128142A (en) * 1986-02-03 1992-07-07 Elan Corporation, Plc Sustained release drug delivery system
US5039372A (en) * 1988-08-05 1991-08-13 Compagnie Generale Des Etablissements Michelin - Michelin Et Cie Component elements of an apparatus for the manufacture of a tire reinforcement
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
WO1993012797A1 (en) * 1991-12-31 1993-07-08 Istituto Gentili S.P.A. Pharmaceutical compositions containing natural progesterone having a high biological availability
DE4202320A1 (en) * 1992-01-29 1993-08-05 Dierk Dr Knittel Impregnating substrate by contact with supercritical fluid contg. impregnant - followed by conversion of fluid to subcritical state
WO1994018264A1 (en) * 1993-02-11 1994-08-18 Minnesota Mining And Manufacturing Company Methods of polymer impregnation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
SUBRANANIAM B ET AL: "PHARMACEUTICAL PROCESSING WITH SUPERCRITICAL CARBON DIOXIDE" JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 86, no. 8, 1 August 1997, pages 885-890, XP000693966 *
ZIA, HOSSEIN ET AL: "Comparison of nasal insulin powders prepared by supercritical fluid and freeze-drying techniques" PART. SCI. TECHNOL. (1997), 15(3), 217-244 CODEN: PTCHDS;ISSN: 0272-6351, XP002103767 *

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001015664A3 (en) * 1999-08-31 2001-09-20 Bradford Particle Design Plc Coformulation methods and their products
WO2001015664A2 (en) * 1999-08-31 2001-03-08 Bradford Particle Design Limited Coformulation methods and their products
WO2001052981A1 (en) * 2000-01-17 2001-07-26 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for modifying the surfaces of fine-porous adsorbents
JP2003526653A (en) * 2000-03-17 2003-09-09 エウランド インターナショナル ソシエタ ペル アチオニ Preparation method of rapid release formulation using compressed fluid
WO2001068054A1 (en) * 2000-03-17 2001-09-20 Eurand International S.P.A. Process for the preparation of accelerated release formulations using compressed fluids
EP1258241A1 (en) * 2001-05-16 2002-11-20 BIOPROGRESS S.p.A. Method of increasing the bioavailability of nimesulide
GB2392619B (en) * 2001-05-30 2004-10-20 Csir Method of encapsulating an active substance
WO2003013478A3 (en) * 2001-05-30 2003-05-30 Csir Method of encapsulating an active substance
GB2392619A (en) * 2001-05-30 2004-03-10 Csir Method of encapsulating an active substance
FR2825292A1 (en) * 2001-05-30 2002-12-06 Csir New process for coating an active substance with an inter polymeric complex in a supercritical liquid
US7641917B2 (en) 2001-05-30 2010-01-05 Csir Method of encapsulating an active substance
WO2002100456A1 (en) * 2001-06-13 2002-12-19 Boston Scientific Limited Using supercritical fluids to infuse therapeutic on a medical device
JP2004535495A (en) * 2001-07-04 2004-11-25 デグサ アクチエンゲゼルシャフト Physical treatment of starch (-derivative)
US7390411B2 (en) 2001-10-12 2008-06-24 Pierre Fabre Medicament Method for preparing a compound of interaction of active substances with a porous support using supercritical fluid
WO2003045448A1 (en) * 2001-11-20 2003-06-05 The University Of Nottingham Impregnation of polymeric substrates with antimicrobial substances using superficial fluids
WO2003074028A1 (en) * 2002-03-07 2003-09-12 Eurand Pharmaceuticals Ltd. Process for loading and thermodynamically activating drugs on polymers by means of supercritical fluids
EP2289561A1 (en) 2003-04-25 2011-03-02 Pierre Fabre Médicament Method for preparing molecular complexes
US8741346B2 (en) 2003-04-25 2014-06-03 Pierre Fabre Medicament Method for the preparation of molecular complexes
US7507823B2 (en) 2004-05-06 2009-03-24 Bristol-Myers Squibb Company Process of making aripiprazole particles
EP1611877A1 (en) 2004-06-28 2006-01-04 Universidade de Coimbra Method for preparing sustained-release therapeutic ophthalmic articles using compressed fluids for impregnation of drugs
GB2417900A (en) * 2004-09-11 2006-03-15 Medway Science Technologies Lt Composition for oral drug delivery
US9226900B2 (en) 2008-07-11 2016-01-05 Critical Pharmaceuticals Limited Process for preparing microparticles
FR2945449A1 (en) * 2009-05-15 2010-11-19 Pf Medicament SUPERCRITICAL CO2 IMPREGNATION PROCESS
WO2010130799A3 (en) * 2009-05-15 2011-05-19 Pierre Fabre Medicament Method for impregnation with supercritical co2
US9028806B2 (en) 2009-05-15 2015-05-12 Pierre Fabre Medicament Method for impregnation with supercritical CO2
CN105687141A (en) * 2016-03-04 2016-06-22 中国药科大学 Technical study for preparing Nim-PLLA (nimesulide-poly-l-lactic acid) composite microsphere with supercritical anti-solvent method
CN112812355A (en) * 2020-12-31 2021-05-18 厦门天生爱科技有限公司 Functional polymer foaming material with slow-release volatile Chinese herbal medicine effective components, preparation method and application
CN113425895A (en) * 2021-07-12 2021-09-24 大连大学 Drug-loaded bone repair internal fixation material and preparation method thereof

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NZ505290A (en) 2002-08-28
AU738748B2 (en) 2001-09-27
BR9814656A (en) 2000-10-03
AU2153199A (en) 1999-06-07
KR20010032251A (en) 2001-04-16
JP2001522873A (en) 2001-11-20
ITMI972571A1 (en) 1999-05-19
IT1296464B1 (en) 1999-06-25

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