AU738748B2 - 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
- AU738748B2 AU738748B2 AU21531/99A AU2153199A AU738748B2 AU 738748 B2 AU738748 B2 AU 738748B2 AU 21531/99 A AU21531/99 A AU 21531/99A AU 2153199 A AU2153199 A AU 2153199A AU 738748 B2 AU738748 B2 AU 738748B2
- Authority
- AU
- Australia
- Prior art keywords
- cross
- linked
- drug
- polymer
- supercritical fluid
- 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.)
- Ceased
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
-
- 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
Description
WO 99/25322 PCT/EP98/07311 1 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 Krukonis, Proc. III International 0o 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 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 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 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 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 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 WO 99/25322 PCT/EP98/07311 2 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 crosslinked polymer; Simpregnation 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 (CO 2 is taken to conditions higher than 31 C and 73.8 bar; ethylene higher than 9 0 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 (N 2 0) higher than 36.4"C and 72.45 bar, in the case of a mixture of carbon dioxide (C0 2 mixed with methanol 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, WO 99/25322 PCT/EP98/07311 3 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 crosslinked 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, WO 99/25322 PCT/EP98/07311 4 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 grams of polymer, cross-linked polyvinyl pyrrolidone, placed in a column of cm length and 0.6 cm size, are contacted with CO 2 saturated with nimesulide at 160 bar and 60 Co. The flux of the incoming stream of saturated CO 2 expressed in flow of liquid CO 2 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 grams of polymer, cross-linked polymethyl methacrylate, placed in a column of cm length and 0.6 cm size, are contacted with CO 2 saturated with acyclovir at 220 bar and 50 the flux of the incoming stream of saturated CO 2 expressed in flow of liquid CO 2 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 CO 2 saturated with the drug.
The reactor is washed first with CO 2 and then a stream of CO 2 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 WO 99/25322 PCTIEP98/07311 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.
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. AMENDED SHEET
Applications Claiming Priority (3)
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 | ||
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 (2)
Publication Number | Publication Date |
---|---|
AU2153199A AU2153199A (en) | 1999-06-07 |
AU738748B2 true AU738748B2 (en) | 2001-09-27 |
Family
ID=11378230
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU21531/99A Ceased 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 |
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 |
ATE298266T1 (en) * | 2000-01-17 | 2005-07-15 | Fraunhofer Ges Forschung | 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 |
EP1401404B1 (en) | 2001-05-30 | 2008-04-16 | Csir | Method of encapsulating 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 |
EP1515699B1 (en) * | 2002-03-07 | 2009-02-04 | Eurand Pharmaceuticals Ltd. | Process for loading and thermodynamically activating drugs on polymers by means of 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 |
EP1968553A2 (en) * | 2005-11-09 | 2008-09-17 | Novartis AG | Process for making pharmaceutical compositions with a transient 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 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994018264A1 (en) * | 1993-02-11 | 1994-08-18 | Minnesota Mining And Manufacturing Company | Methods of polymer impregnation |
Family Cites Families (5)
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 |
-
1997
- 1997-11-19 IT IT97MI002571A patent/IT1296464B1/en active IP Right Grant
-
1998
- 1998-11-16 AU AU21531/99A patent/AU738748B2/en not_active Ceased
- 1998-11-16 CA CA002310423A patent/CA2310423A1/en not_active Abandoned
- 1998-11-16 WO PCT/EP1998/007311 patent/WO1999025322A2/en not_active Application Discontinuation
- 1998-11-16 EP EP98965674A patent/EP1033977A2/en not_active Withdrawn
- 1998-11-16 JP JP2000520756A patent/JP2001522873A/en active Pending
- 1998-11-16 KR KR1020007005454A patent/KR20010032251A/en not_active Application Discontinuation
- 1998-11-16 BR BR9814656-4A patent/BR9814656A/en not_active IP Right Cessation
- 1998-11-16 NZ NZ505290A patent/NZ505290A/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994018264A1 (en) * | 1993-02-11 | 1994-08-18 | Minnesota Mining And Manufacturing Company | Methods of polymer impregnation |
Non-Patent Citations (1)
Title |
---|
HOSSEIN ZIA ET AL PART. SCIENCE & TECH. 15 (3)PP273-301 * |
Also Published As
Publication number | Publication date |
---|---|
BR9814656A (en) | 2000-10-03 |
KR20010032251A (en) | 2001-04-16 |
ITMI972571A1 (en) | 1999-05-19 |
AU2153199A (en) | 1999-06-07 |
WO1999025322A2 (en) | 1999-05-27 |
IT1296464B1 (en) | 1999-06-25 |
WO1999025322A3 (en) | 1999-08-19 |
NZ505290A (en) | 2002-08-28 |
EP1033977A2 (en) | 2000-09-13 |
CA2310423A1 (en) | 1999-05-27 |
JP2001522873A (en) | 2001-11-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU738748B2 (en) | Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids | |
Karanth et al. | Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report | |
TWI230079B (en) | Solid pharmaceutical dispersions with enhanced bioavailability | |
Sharma et al. | Solid dispersion: A promising technique to enhance solubility of poorly water soluble drug | |
CN101193624B (en) | Production of solid solutions based on poorly-soluble active substances by a short-term heating and rapid drying | |
IL153231A (en) | Wet milling process | |
WO2007109604A2 (en) | Pharmaceutical compositions | |
ES2228148T3 (en) | METHOD OF PRODUCTION OF PARTICLES OF PHARMACOS. | |
JP2005516923A5 (en) | ||
Aggarwal et al. | Solid dispersion as an eminent strategic approach in solubility enhancement of poorly soluble drugs | |
JPH05320045A (en) | Spray drying method for manufacturing medicine powder composition being compressable directly to tablet | |
CA2397404A1 (en) | Micronized freeze-dried particles | |
EP2258368A3 (en) | Pharmaceutical compositions for nasal delivery | |
JP4754830B2 (en) | Apparatus and method for isolating produced particles as a suspension in a non-supercritical fluid | |
EP1515699B1 (en) | Process for loading and thermodynamically activating drugs on polymers by means of supercritical fluids | |
US20090221761A1 (en) | Process for removing residual volatile monomers from a polymer in powder form | |
WO2004071494A2 (en) | Lipophilic compositions | |
US20090203789A1 (en) | Fast Dissolution Amino Acid Composition | |
KR20020031416A (en) | Pharmaceutical preparation containing nanosol | |
Patel et al. | LIQUISOLID COMPACTS: AN EFFECTIVE APPROACH TOWARDS ENHANCEMENT OF DISSOLUTION RATE OF POORLY SOLUBLE DRUGS. | |
Abbas et al. | Preparation and Characterization of Bilastine Solid Self-Nanoemulsion using Liquisolid Technique | |
EP1341525B1 (en) | Granulation process using halogenated hydrocarbon | |
JPH0344319A (en) | Overdischargeing-suppressing antacid | |
Tomar et al. | Solubility Enhancement by Solid Dispersion-A Review | |
WO2008156356A1 (en) | Preparation of a pharmaceutically active ingredient comprising a desolventising step |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FGA | Letters patent sealed or granted (standard patent) |