AU2153199A - 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

Info

Publication number
AU2153199A
AU2153199A AU21531/99A AU2153199A AU2153199A AU 2153199 A AU2153199 A AU 2153199A AU 21531/99 A AU21531/99 A AU 21531/99A AU 2153199 A AU2153199 A AU 2153199A AU 2153199 A AU2153199 A AU 2153199A
Authority
AU
Australia
Prior art keywords
cross
linked
polymers
drug
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.)
Granted
Application number
AU21531/99A
Other versions
AU738748B2 (en
Inventor
Paolo Alessi
Fabio Carli
Italo Colombo
Angelo Cortesi
Ireneo Kikic
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 Int SpA
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 Int SpA, Eurand International SpA filed Critical Eurand Int SpA
Publication of AU2153199A publication Critical patent/AU2153199A/en
Application granted granted Critical
Publication of AU738748B2 publication Critical patent/AU738748B2/en
Anticipated expiration legal-status Critical
Ceased 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

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)

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 5 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 10 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, 15 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. 20 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 25 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. 30 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/IEP98/07311 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; 5 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 10 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 15 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 90C and 54.4 bar; methane higher than -82*C and 46.0 bar; propylene higher than 920C and 46.2 bar; nitrous oxide (N 2 0) higher than 36.40C and 72.45 bar, in the case of a 20 mixture of carbon dioxide (CO 2 ) mixed with methanol (7%) it is taken to conditions above 400C 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 25 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 30 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 5 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 10 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 15 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, 20 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 25 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 30 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/IEP98/07311 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. 5 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: 10 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 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, 15 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 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 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 25 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 C02 saturated with the drug. The reactor is washed first with C02 and then a stream of C02 saturated with 30 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 PCT/IEP98/07311 5 hour, 2 hours, the concentrations of drug in the polymers are 22.2; 25.6; 15.3; and 20.4% respectively.

Claims (9)

1. Pharmaceutical compositions in form of powders consisting of cross-linked polymers loaded with active principles by an impregnation process with supercritical fluids. 5
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 10 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 15 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. 20
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 25 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. 30
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.
AU21531/99A 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 Ceased AU738748B2 (en)

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 (2)

Publication Number Publication Date
AU2153199A true AU2153199A (en) 1999-06-07
AU738748B2 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)

* Cited by examiner, † Cited by third party
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 (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
CN1255099C (en) 2001-05-30 2006-05-10 South African Scientific and Industrial Research Center Method for encapsulating 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
KR101374928B1 (en) * 2005-11-09 2014-03-14 노파르티스 아게 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

Family Cites Families (6)

* Cited by examiner, † Cited by third party
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

Also Published As

Publication number Publication date
CA2310423A1 (en) 1999-05-27
WO1999025322A3 (en) 1999-08-19
NZ505290A (en) 2002-08-28
BR9814656A (en) 2000-10-03
KR20010032251A (en) 2001-04-16
ITMI972571A1 (en) 1999-05-19
JP2001522873A (en) 2001-11-20
EP1033977A2 (en) 2000-09-13
WO1999025322A2 (en) 1999-05-27
AU738748B2 (en) 2001-09-27
IT1296464B1 (en) 1999-06-25

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
CA2462338C (en) Powder processing with pressurized gaseous fluids
ES2228148T3 (en) METHOD OF PRODUCTION OF PARTICLES OF PHARMACOS.
IL153231A (en) Wet milling process
JP2005516923A5 (en)
Shazly et al. Dissolution improvement of solid self-emulsifying drug delivery systems of fenofibrate using an inorganic high surface adsorption material
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
JP4754830B2 (en) Apparatus and method for isolating produced particles as a suspension in a non-supercritical fluid
CA2397404A1 (en) Micronized freeze-dried particles
WO2004075824A8 (en) Pharmaceutical compositions for nasal delivery
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
Foster et al. Particle engineering by dense gas technologies applied to pharmaceuticals
Ukita et al. Preparation of essential oils loaded granule by melt granulation
WO2004071494A2 (en) Lipophilic compositions
JP5513745B2 (en) Method for preparing particles comprising a biological molecule and a carrier polymer
Patel et al. LIQUISOLID COMPACTS: AN EFFECTIVE APPROACH TOWARDS ENHANCEMENT OF DISSOLUTION RATE OF POORLY SOLUBLE DRUGS.
EP1341525B1 (en) Granulation process using halogenated hydrocarbon
Leboeuf et al. Supercritical fluid processing in food and pharmaceutical industries: Scale-up issues
HRP20030543A2 (en) Stable granulates containing s-adenosylmethionine and process for the preparation thereof
CN115590835A (en) Preparation method of lurasidone
Tomar et al. Solubility Enhancement by Solid Dispersion-A Review
JPH0344319A (en) Overdischargeing-suppressing antacid

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)