CA2349202A1 - Method of preparing stable suspensions of insoluble microparticles - Google Patents

Method of preparing stable suspensions of insoluble microparticles Download PDF

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Publication number
CA2349202A1
CA2349202A1 CA002349202A CA2349202A CA2349202A1 CA 2349202 A1 CA2349202 A1 CA 2349202A1 CA 002349202 A CA002349202 A CA 002349202A CA 2349202 A CA2349202 A CA 2349202A CA 2349202 A1 CA2349202 A1 CA 2349202A1
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Prior art keywords
agent
hlb
surfactant
phospholipid
surface modifier
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Granted
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CA002349202A
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French (fr)
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CA2349202C (en
Inventor
Sheema Khan
Indu Parikh
Helen C. Loughrey
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Jagotec AG
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Individual
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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
    • 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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K9/145—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 compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Virology (AREA)
  • Transplantation (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Anesthesiology (AREA)
  • Diabetes (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Sub-micron and micron-size stable particles of water-insoluble or poorly soluble drugs or other industrially useful insoluble compounds suspended in an aqueous medium containing at least one surface modifier are prepared by selecting the surface modifier or modifiers such that the hydrophile-lipophi le balance (HLB) of the composition, defined as formula (I): is between 4 and 9 . This provides a reliable HLB-based selection criteria for selecting the type and amount of surface modifiers used to obtain sub-micron size stable suspensions.

Claims (10)

1. A method of preparing stable micron or sub-micron size suspensions of a water-insoluble or poorly soluble compound suspended in an aqueous medium containing at least one surface modifier, the method comprising selecting the surface modifier or modifiers such that the hydrophile-lipophile balance (HLB) of the composition , defined as:
System HLB = x (HLB value of surfactant j) is between 4 and 9.
2. A method of preparing a stable micron or sub-micron size suspension of a water-insoluble or poorly soluble compound in an aqueous medium containing a phospholipid and at least one surfactant, the method comprising selecting the surfactant or surfactants such that the HLB of the composition , defined as:
System HLB = x (HLB value of surfactant j) is between 4 and 9.
3. The method of claim 1 wherein the HLB value of the surface modifier or modifiers is between 5 and 35.
4. The method of claim 2 wherein the HLB of the surfactant is between 5 and 35.
5. The method of claim 1 wherein the surface modifier is a polyoxyethylene sorbitan fatty acid ester, a block copolymer of ethylene oxide and propylene oxide, polyoxyethylene stearate a tetrafunctional block copolymer derived from sequential addition of ethylene oxide and propylene oxide to ethylenediamine, an alkyl aryl polyether sulfonate, polyethylene glycol, hydroxy propylmethylcellulose, polyvinylpyrrolidone and polyvinyl alcohol.
6. The method of claim 2 wherein the surfactant is a polyoxyethylene sorbitan fatty acid ester polyoxyethylene stearate, a block copolymer of ethylene oxide, and propylene oxide, a tetra functional block copolymer derived from sequential addition of ethylene oxide and propylene oxide to ethylenediamine, an alkyl aryl polyether sulfonate, polyethylene glycol, hydroxy propylmethylcellulose, polyvinylpyrrolidone and polyvinyl alcohol.
7. The method of claim 2 wherein the phospholipid is desalted, hydrogenated or partially hydrogenated or natural, semisynthetic or synthetic.
8. The method of claim 7 wherein the phospholipid is phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinoistol, phosphatidylglycerol, phosphatidic acid lysophospholipids, egg or soybean phospholipid or a combination thereof.
9. The method of claim 1 or claim 2 wherein the water insoluble or poorly water soluble compound is an antifungal agent, immunosuppressive or immunoactive agent, antiviral agent, antineoplastic agent, analgesic or anti-inflammatory agent, antibiotic, antiepileptic, anesthetic, hypnotic, sedative, antipsychotic agent, neuroleptic agent, antidepressant, anxiolytic, anticonvulsant agent, antagonist, neuron blocking agent, anticholinergic or cholinomimetic agent, antimuscarinic or muscarinic agent, antiadrenergic, and antarrhythmic, antihypertensive agent hormone or a nutrient.
10. A drug composition prepared by the method of claim 1 comprising a phospholipid and a surfactant wherein the HLB value of the composition is between 4 and 9 and which following lyophilization the reconstitution maintains substantially the same particle size.
CA2349202A 1998-11-20 1999-11-19 Method of preparing stable suspensions of insoluble microparticles Expired - Fee Related CA2349202C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US10920398P 1998-11-20 1998-11-20
US60/109,203 1998-11-20
PCT/US1999/027435 WO2000030615A1 (en) 1998-11-20 1999-11-19 Method of preparing stable suspensions of insoluble microparticles

Publications (2)

Publication Number Publication Date
CA2349202A1 true CA2349202A1 (en) 2000-06-02
CA2349202C CA2349202C (en) 2012-06-19

Family

ID=22326359

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2349202A Expired - Fee Related CA2349202C (en) 1998-11-20 1999-11-19 Method of preparing stable suspensions of insoluble microparticles

Country Status (8)

Country Link
EP (1) EP1133280A1 (en)
JP (1) JP5296954B2 (en)
KR (1) KR20010075713A (en)
CN (1) CN1213733C (en)
AU (1) AU767737B2 (en)
CA (1) CA2349202C (en)
IL (2) IL143196A0 (en)
WO (1) WO2000030615A1 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4751556B2 (en) * 2000-02-28 2011-08-17 ジーンシーグス， インコーポレイテッド Nanocapsule encapsulation system and method
AR035642A1 (en) 2000-05-26 2004-06-23 Pharmacia Corp USE OF A CELECOXIB COMPOSITION FOR QUICK PAIN RELIEF
US8067032B2 (en) 2000-12-22 2011-11-29 Baxter International Inc. Method for preparing submicron particles of antineoplastic agents
US9700866B2 (en) 2000-12-22 2017-07-11 Baxter International Inc. Surfactant systems for delivery of organic compounds
FR2819720B1 (en) 2001-01-22 2004-03-12 Fournier Lab Sa NEW FENOFIBRATE TABLETS
GB0119480D0 (en) 2001-08-09 2001-10-03 Jagotec Ag Novel compositions
JP2005504090A (en) 2001-09-26 2005-02-10 バクスター・インターナショナル・インコーポレイテッド Preparation of submicron size-nanoparticles by removal of dispersion and solvent or liquid phase
US20060003012A9 (en) 2001-09-26 2006-01-05 Sean Brynjelsen Preparation of submicron solid particle suspensions by sonication of multiphase systems
UY27939A1 (en) 2002-08-21 2004-03-31 Glaxo Group Ltd COMPOUNDS
US7828996B1 (en) 2009-03-27 2010-11-09 Abbott Cardiovascular Systems Inc. Method for the manufacture of stable, nano-sized particles
CN104053668B (en) * 2011-11-30 2020-09-11 新加坡科技研究局 Microparticle polypeptide ratio of GM1 ganglioside to annexin V for biological assays
CN114367383B (en) * 2022-01-13 2024-01-09 苏州丰倍生物科技股份有限公司 Fatty acid ester nano suspension, preparation method and application thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2651680B1 (en) * 1989-09-14 1991-12-27 Medgenix Group Sa NOVEL PROCESS FOR THE PREPARATION OF LIPID MICROPARTICLES.
US5091187A (en) * 1990-04-26 1992-02-25 Haynes Duncan H Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs
RO120603B1 (en) * 1996-08-22 2006-05-30 Research Triangle Pharmaceuticals Ltd. Composition containing microparticles of water-insoluble substances and process for preparing the same
WO1999049846A2 (en) * 1998-03-30 1999-10-07 Rtp Pharma Inc. Compositions containing microparticles of water-insoluble substances and method for their preparation
CN1245955C (en) * 1998-05-29 2006-03-22 斯凯伊药品加拿大公司 Thermoprotected microparticle compositions and process for terminal steam sterilization thereof

Also Published As

Publication number Publication date
WO2000030615A1 (en) 2000-06-02
JP5296954B2 (en) 2013-09-25
IL143196A (en) 2012-01-31
CA2349202C (en) 2012-06-19
CN1213733C (en) 2005-08-10
AU1737400A (en) 2000-06-13
CN1337877A (en) 2002-02-27
KR20010075713A (en) 2001-08-09
IL143196A0 (en) 2002-04-21
EP1133280A1 (en) 2001-09-19
AU767737B2 (en) 2003-11-20
JP2002530320A (en) 2002-09-17

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