CA2310423A1 - 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 PDFInfo
- Publication number
- CA2310423A1 CA2310423A1 CA002310423A CA2310423A CA2310423A1 CA 2310423 A1 CA2310423 A1 CA 2310423A1 CA 002310423 A CA002310423 A CA 002310423A CA 2310423 A CA2310423 A CA 2310423A CA 2310423 A1 CA2310423 A1 CA 2310423A1
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- Canada
- Prior art keywords
- cross
- drug
- linked
- polymer
- supercritical fluid
- Prior art date
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Classifications
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- 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
- A61K9/141—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
- 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
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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
s 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. III International io 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, is Biotechnol. Prog., 3, 73, 1986) in the operations of extraction and purification (G.
Brunner, peas 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.
2o 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 2s 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.
3o 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;
s ~ contacting the supercritical fluid containing the solubilized drug with the cross-linked polymer;
~ impregnation of the cross-linked polymer with the supercritical fluid containing the drug;
~ removal of the supercritical fluid with consequent loading of the drug in the io 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 ~s conditions higher than those at which it can be considered as supercritical. For example, in the case of pure components, carbon dioxide (C02) 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 (NZO) higher than 36.4°C and 72.45 bar , in the case of a 2o mixture of carbon dioxide (C02) 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 2s 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 solubiiized 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 3o 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, WO 99/Z5322 pGT/EP98107311 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 s 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 ~o 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 is 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, 2o 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 2s mention, as an however not exhaustive exemplification:
Analgesics and non steroidal antiinflammatories and their salts: sodium diciofenac, ibuprofen, naproxen, etc.; antibactericals: amoxicillin, cephalosporins, etc.; antifungals and antipsoriatics: ketoconazole, griseofulvin, itraconazole, thioconazole, etc.; antivirals: acyclovir, gancyclovir, etc.; antineoplastics and 3o 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.
s The compositions are formulated as packets or as tables, perles pellets or granules for pharmaceutical use.
E)CAMPLE,,$
For the illustrative aim of the invention the following examples are reported hereinafter:
to Example No. 1 grams of polymer, cross-linked polyvinyl pyrrolidone, placed in a column of 50 cm length and 0.6 cm size, are contacted with C02 saturated with nimesulide at 160 bar and 60 C°. The flux of the incoming stream of saturated C02 expressed in flow of liquid C02 is equal to 0.1 litres/minute. At the end of the test, after 8 hours, is 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 potymethyl methacrylate, placed in a column of 50 cm length and 0.6 cm size, are contacted with C02 saturated with acyclovir at 20 220 bar and 50 C°: the flux of the incoming stream of saturated C02 expressed in flow of liquid C02 is equal to 0.1 litreslminute.
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 2s 15 grams of polymeric materials (respectively physically cross-linked polyvinyl pyrrolidone, chemically cross-linked polyvinyl pyrrolidone, cross-linked sodium starch giycolate and acrylic acid cross-linked with allilic esters of sucrose) are put into a 200 ml reactor and contacted with C02 saturated with the drug.
The reactor is washed first with C02 and then a stream of C02 saturated with 3o 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 WO 991253ZZ pCTIEP98H17311 hour, 2 hours, the concentrations of drug in the polymers are 22.2; 25.6;
15.3; and 20.4% respectively.
CROSS-LINKED POLYMERS LOADED WITH DRUGS AND RELATED
PREPARATION PROCESS BY SUPERCRITICAL FLUIDS
FIELD OF THE INVENTION
s 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. III International io 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, is Biotechnol. Prog., 3, 73, 1986) in the operations of extraction and purification (G.
Brunner, peas 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.
2o 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 2s 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.
3o 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;
s ~ contacting the supercritical fluid containing the solubilized drug with the cross-linked polymer;
~ impregnation of the cross-linked polymer with the supercritical fluid containing the drug;
~ removal of the supercritical fluid with consequent loading of the drug in the io 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 ~s conditions higher than those at which it can be considered as supercritical. For example, in the case of pure components, carbon dioxide (C02) 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 (NZO) higher than 36.4°C and 72.45 bar , in the case of a 2o mixture of carbon dioxide (C02) 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 2s 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 solubiiized 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 3o 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, WO 99/Z5322 pGT/EP98107311 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 s 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 ~o 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 is 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, 2o 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 2s mention, as an however not exhaustive exemplification:
Analgesics and non steroidal antiinflammatories and their salts: sodium diciofenac, ibuprofen, naproxen, etc.; antibactericals: amoxicillin, cephalosporins, etc.; antifungals and antipsoriatics: ketoconazole, griseofulvin, itraconazole, thioconazole, etc.; antivirals: acyclovir, gancyclovir, etc.; antineoplastics and 3o 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.
s The compositions are formulated as packets or as tables, perles pellets or granules for pharmaceutical use.
E)CAMPLE,,$
For the illustrative aim of the invention the following examples are reported hereinafter:
to Example No. 1 grams of polymer, cross-linked polyvinyl pyrrolidone, placed in a column of 50 cm length and 0.6 cm size, are contacted with C02 saturated with nimesulide at 160 bar and 60 C°. The flux of the incoming stream of saturated C02 expressed in flow of liquid C02 is equal to 0.1 litres/minute. At the end of the test, after 8 hours, is 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 potymethyl methacrylate, placed in a column of 50 cm length and 0.6 cm size, are contacted with C02 saturated with acyclovir at 20 220 bar and 50 C°: the flux of the incoming stream of saturated C02 expressed in flow of liquid C02 is equal to 0.1 litreslminute.
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 2s 15 grams of polymeric materials (respectively physically cross-linked polyvinyl pyrrolidone, chemically cross-linked polyvinyl pyrrolidone, cross-linked sodium starch giycolate and acrylic acid cross-linked with allilic esters of sucrose) are put into a 200 ml reactor and contacted with C02 saturated with the drug.
The reactor is washed first with C02 and then a stream of C02 saturated with 3o 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 WO 991253ZZ pCTIEP98H17311 hour, 2 hours, the concentrations of drug in the polymers are 22.2; 25.6;
15.3; and 20.4% respectively.
Claims (7)
1. Process for the preparation of a pharmaceutical composition consisting of a cross-linked polymer loaded with a drug, characterized by: 1) solubilization of the drug in a supercritical fluid; 2) impregnation of the cross-linked polymer by passing the supercritical fluid containing the drug through a column containing said cross-linked polymer; 3) removal of the supercritical fluid with consequent loading of the drug in the cross-linked polymer itself.
2. Process as claimed in claim 1, characterized in that said impregnation step is carried out by a contact time from 5 minutes to 72 hours.
3. Process as claimed in claim 1, characterized in that said impregnation step is carried out by a contact time from 0.25 hours to 24 hours.
4. Process as claimed in claim 1, characterized in that said cross-linked polymer is selected from the group comprising cross-linked polyvinyl pyrrolidone, cross-linked sodium starch glycolate, cross-linked sodium carboxymethyl cellulose, cross-linked polystirene, and cross-linked polymethyl methacrylate sodium salt.
5. A pharmaceutical composition consisting of a cross-linked polymer loaded with a drug, prepared by a process according to claims 1 to 4, characterized in that said drug is present in an amount ranging from 0.1 to 99.9% by weight with respect to the polymer.
6. A composition as claimed in claim 5, characterized in that said drug is present in an amount ranging from 0.1 to 50% by weight with respect to the polymer.
7. A composition as claimed in claim 5, characterized in that it is formulated as packets or as tablets, perles, pellets or granules, for pharmaceutical use.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI97A002571 | 1997-11-19 | ||
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 |
PCT/EP1998/007311 WO1999025322A2 (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 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2310423A1 true CA2310423A1 (en) | 1999-05-27 |
Family
ID=11378230
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002310423A Abandoned 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 |
Country Status (9)
Country | Link |
---|---|
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) |
Families Citing this family (21)
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 |
EP1250189B1 (en) * | 2000-01-17 | 2005-06-22 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Method for modifying the surfaces of fine-porous adsorbents |
IT1318404B1 (en) * | 2000-03-17 | 2003-08-25 | Eurand Int | PROCESS FOR THE PREPARATION OF FORMULATIONS WITH ACCELERATED RELEASE WITH THE USE OF COMPRESSED FLUIDS. |
EP1258241A1 (en) * | 2001-05-16 | 2002-11-20 | BIOPROGRESS S.p.A. | Method of increasing the bioavailability of nimesulide |
ES2305250T3 (en) | 2001-05-30 | 2008-11-01 | Csir | ENCAPSULATION PROCEDURE OF AN ACTIVE SUBSTANCE. |
US20030044514A1 (en) * | 2001-06-13 | 2003-03-06 | Richard Robert E. | Using supercritical fluids to infuse therapeutic on a medical device |
DE10132366A1 (en) * | 2001-07-04 | 2003-01-30 | Degussa | Process for the physical treatment of starch (derivatives) |
FR2830760B1 (en) | 2001-10-12 | 2004-06-04 | Pf Medicament | PROCESS FOR THE PREPARATION OF AN INTERACTION COMPOUND OF ACTIVE SUBSTANCES WITH A POROUS SUPPORT BY SUPERCRITICAL FLUID |
GB0127786D0 (en) * | 2001-11-20 | 2002-01-09 | Univ Nottingham | Impregnation of antimicrobial substances |
DK1515699T3 (en) * | 2002-03-07 | 2009-05-04 | Eurand Pharmaceuticals Ltd | Process for charge and thermodynamic activation of drugs on polymers by supercritical fluids |
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 |
FR2854079B1 (en) | 2003-04-25 | 2007-11-30 | Pf Medicament | PROCESS 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 |
JP5284101B2 (en) * | 2005-11-09 | 2013-09-11 | ノバルティス アーゲー | Method for producing pharmaceutical composition using temporary plasticizer |
GB0812742D0 (en) | 2008-07-11 | 2008-08-20 | Critical Pharmaceuticals Ltd | Process |
FR2945449B1 (en) * | 2009-05-15 | 2012-10-05 | Pf Medicament | SUPERCRITICAL CO2 IMPREGNATION PROCESS |
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 |
CN112812355B (en) * | 2020-12-31 | 2022-09-23 | 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 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IE63321B1 (en) * | 1986-02-03 | 1995-04-05 | Elan Corp Plc | Drug delivery system |
FR2635043B1 (en) * | 1988-08-05 | 1990-09-28 | Michelin & Cie | APPARATUS FOR MANUFACTURING A REINFORCEMENT FOR TIRES, SAID REINFORCEMENT MADE FROM A SINGLE THREAD |
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 (en) * | 1991-12-31 | 1995-06-28 | Gentili Ist Spa | PHARMACEUTICAL COMPOSITIONS CONTAINING HIGH-BIOAVAILABILITY PROGESTERONE |
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 |
US5340614A (en) * | 1993-02-11 | 1994-08-23 | Minnesota Mining And Manufacturing Company | Methods of polymer impregnation |
-
1997
- 1997-11-19 IT IT97MI002571A patent/IT1296464B1/en active IP Right Grant
-
1998
- 1998-11-16 JP JP2000520756A patent/JP2001522873A/en active Pending
- 1998-11-16 CA CA002310423A patent/CA2310423A1/en not_active Abandoned
- 1998-11-16 NZ NZ505290A patent/NZ505290A/en unknown
- 1998-11-16 EP EP98965674A patent/EP1033977A2/en not_active Withdrawn
- 1998-11-16 BR BR9814656-4A patent/BR9814656A/en not_active IP Right Cessation
- 1998-11-16 AU AU21531/99A patent/AU738748B2/en not_active Ceased
- 1998-11-16 WO PCT/EP1998/007311 patent/WO1999025322A2/en not_active Application Discontinuation
- 1998-11-16 KR KR1020007005454A patent/KR20010032251A/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
NZ505290A (en) | 2002-08-28 |
WO1999025322A3 (en) | 1999-08-19 |
JP2001522873A (en) | 2001-11-20 |
WO1999025322A2 (en) | 1999-05-27 |
ITMI972571A1 (en) | 1999-05-19 |
BR9814656A (en) | 2000-10-03 |
EP1033977A2 (en) | 2000-09-13 |
IT1296464B1 (en) | 1999-06-25 |
AU2153199A (en) | 1999-06-07 |
KR20010032251A (en) | 2001-04-16 |
AU738748B2 (en) | 2001-09-27 |
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