WO2000057859A1 - Novel formulations comprising lipid-regulating agents - Google Patents

Novel formulations comprising lipid-regulating agents Download PDF

Info

Publication number
WO2000057859A1
WO2000057859A1 PCT/US2000/007650 US0007650W WO0057859A1 WO 2000057859 A1 WO2000057859 A1 WO 2000057859A1 US 0007650 W US0007650 W US 0007650W WO 0057859 A1 WO0057859 A1 WO 0057859A1
Authority
WO
WIPO (PCT)
Prior art keywords
oil
composition
lipid
fatty acid
delivery system
Prior art date
Application number
PCT/US2000/007650
Other languages
French (fr)
Inventor
Jitendra P. Patel
Yeshwant D. Sanzgiri
John M. Lipari
Thomas L. Reiland
Original Assignee
Abbott Laboratories
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 Abbott Laboratories filed Critical Abbott Laboratories
Priority to CA002365128A priority Critical patent/CA2365128A1/en
Priority to AU40211/00A priority patent/AU4021100A/en
Priority to JP2000607610A priority patent/JP2003520767A/en
Priority to EP00919545A priority patent/EP1162954A1/en
Priority to MXPA01009840A priority patent/MXPA01009840A/en
Publication of WO2000057859A1 publication Critical patent/WO2000057859A1/en
Priority to HK02104038.4A priority patent/HK1043936A1/en

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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Botany (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention is directed to a formulation comprising a lipid-regulating agent dissolved or dispersed in at least one oil and an emulsifier or emulsifier blend, the resulting mixture being capable of forming an emulsion upon dilution in an aqueous medium.

Description

Novel Formulations Comprising Lipid-Regulating Agents
Field of the Invention
The present invention relates to novel formulations comprising lipid-regulating agents.
Background of the Invention
2- [4- (4-chlorobenzoyl) phenoxy] -2 -methyl-propanoic acid, 1-methylethylester, also known as fenofibrate, is representative of a broad class of compounds having pharmaceutical utility as lipid regulating agents. More specifically, this compound is part of a lipid-regulating agent class of compounds commonly known as fibrates, and is disclosed in U.S. Patent No. 4,058,552.
Fenofibrate has been prepared in several different formulations, c.f., U.S. Patent No. 4,800,079 and U.S. Patent No. 4,895,726. U.S. Patent No. 4,895,726 discloses a co- micronized formulation of fenofibrate and a solid surfactant.
U.S. Patent No. 4,961,890 discloses a process for preparing a controlled release formulation containing fenofibrate in an intermediate layer in the form of crystalline microparticles included within pores of an inert matrix. The formulation is prepared by a process involving the sequential steps of dampening said inert core with a solution based on said binder, then projecting said fenofibrate microparticles in a single layer onto said dampened core, and thereafter drying, before said solution based on said binder dissolves said fenofibrate microparticles, and repeating said three steps in sequence until said intermediate layer is formed. European Patent Application No. EP0793958A2 discloses a process for producing a fenofibrate solid dosage form utilizing fenofibrate, a surface active agent and polyvinyl pyrrolidone in which the fenofibrate particles are mixed with a polyvinyl pyrrolidone solution. The thus obtained mixture is granulated with an aqueous solution of one or more surface active agents, and the granulate thus produced is dried.
PCT Publication No. WO 82/01649 discloses a fenofibrate formulation having granules that are comprised of a neutral core that is a mixture of saccharose and starch. The neutral core is covered with a first layer of fenofibrate, admixed with an excipient and with a second microporous outer layer of an edible polymer.
U.S. Patent No. 5,645,856 describes the use of a carrier for hydrophobic drugs, including fenofibrate, and pharmaceutical compositions based thereon. The carrier comprises a digestible oil and a pharmaceutically-acceptable surfactant component for dispersing the oil in vivo upon administration of the carrier, which comprises a hydrophilic surfactant, said surfactant component being such as not to substantially inhibit the in vivo lipolysis of the digestible oil.
Gemfibrozil is another member of the fibrate class of lipid-regulating agents. U.S. Patent No. 4,927,639 discloses a disintegratable formulation of gemfibrozil providing both immediate and sustained release, comprising a tablet compressed from a mixture of a first and second granulation, and a disintegration excipient operable to effect partial or complete disintegration in the stomach. The first granulation comprises finely divided particles of pure gemfibrozil granulated with at least one cellulose derivative, and the second granulation comprises finely divided particles of pure gemfibrozil granulated with a pharmaceutically-acceptable water soluble or insoluble polymer which are then uniformly coated with a pharmaceutically-acceptable (meth) acrylate copolymer prior to admixture with the first granulation. The first and second granulations are present in the final composition in a ratio of from about 10:1 to about 1:10.
U.S. Patent 4,925,676 discloses a disintegratable gemfibrozil tablet providing both immediate and enteric release, which is compressed from a mixture of a first granulation of gemfibrozil with at least one acid- disintegratable binder, and a second granulation formed from the first granulation, but regranulated or coated with an alkali-disintegratable formulation of at least one substantially alkali-soluble and substantially acid-insoluble polymer.
Another class of lipid-regulating agents are commonly known as statins, of which pravastatin and atorvastatin are members. U.S. Patents 5,030,447 and 5,180,589 describe stable pharmaceutical compositions, which when dispersed in water have a pH of at least 9, and include a medicament which is sensitive to a low pH environment, such as pravastatin, one or more fillers such as lactose and/or microcrystalline cellulose, one or more binders, such as microcrystalline cellulose (dry binder) or polyvinylpyrrolidone (wet binder) , one or more disintegrating agents such as croscarmellose sodium, one or more lubricants such as magnesium stearate and one or more basifying agents such as magnesium oxide.
It is an object of the present invention to provide formulations of lipid-regulating agents having enhanced bioavailability and longer half-life when compared to commercially available formulations. Summary of the Invention
The present invention is directed to a formulation comprising a lipid-regulating agent dissolved in an oil, with subsequent emulsification using one or more emulsifiers. This formulation forms fine and stable emulsions. The emulsions result in an increase in drug solubility, oral bioavailability and half-life.
The formulation may be administered directly, diluted into an appropriate vehicle for administration, encapsulated into soft or hard gelatin shells or capsules for administration, or administered by other means obvious to those skilled in the art.
Brief Description of the Drawings
Figure 1 is a graph showing the plasma concentration in fasted dogs of the formulation of Example 1 and a reference compound .
Detailed Description of the Invention
The bulk lipid-regulating agent may be prepared by any available method, as for example the compound fenofibrate may be prepared by the procedure disclosed in U.S. Patent No. 4,058,552, or the procedure disclosed in U.S. Patent No. 4,739,101, both herein incorporated by reference.
The solution comprising the lipid-regulating agent is prepared by dissolving said agent in the oil with adequate mixing. An emulsifier or emulsifier blend is added to said mixture and mixed until uniform. If desired, water can be then added to the resulting mixture with agitation to form a uniform emulsion.
The delivery system of the present invention results in increased solubility, half-life and bioavailability of the lipid-regulating agent. It can be further diluted with additional liquids or it may be thickened and/or stabilized with various pharmaceutical excipients to vary its existing properties .
Suitable oils include, but are not limited to, any pharmaceutically acceptable oil, such as, for example, soybean oil, coconut oil, canola oil, corn oil, palm kernel oil, cottonseed oil, olive oil, peanut oil, safflower oil and sesame oil.
Suitable emulsifiers include any pharmaceutically acceptable hydrophilic or lipophilic emulsifier or combinations thereof, such as, for example, phospholipids, polyoxyethylene sorbitan fatty acid derivatives, sorbitan fatty acid derivatives, polyoxyl -35 -castor oil (Cremophor EL, available from BASF) , castor oil or hydrogenated castor oil ethoxylates, polyglycerol esters of fatty acids, fatty acid ethoxylates, alcohol ethoxylates, polyoxyethylene- polyoxypropylene co-polymers and block co-polymers, and TPGS (d-alpha tocopheryl polyethylene glycol 1000 succinate) . Preferred emulsifiers include polyoxyethylene sorbitan fatty acid derivatives, sorbitan fatty acid derivatives and polyoxyl-35-castor oil (Cremophor EL, available from BASF) .
Other optional ingredients which may be included in the compositions of the present invention are those which are conventionally used in oil-based drug delivery systems, e.g. antioxidants such as, for example, tocopherol, ascorbyl palmitate, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, propyl gallate, etc.; pH stabilizers such as, for example, citric acid, tartaric acid, fumaric acid, acetic acid, glycine, arginine, lysine, potassium hydrogen phosphate, etc.; thickeners/suspending agents such as, for example, hydrogenated vegetable oils, beeswax, colloidal silicon dioxide, gums, celluloses, silicates, bentonite, etc.; flavoring agents such as, for example, cherry, lemon, aniseed flavors, etc.; sweeteners such as, for example, aspartame, saccharin, cyclamates, etc.; and co-solvents, such as, for example, ethanol, propylene glycol, polyethylene glycol, dimethyl isosorbide, etc.
The resulting liquid comprising the lipid-regulating agent may be dosed directly for oral administration, diluted into an appropriate vehicle for oral administration, filled into soft or hard shells or capsules for oral administration, or delivered by some other means obvious to those skilled in the art. The said liquid can be used to improve the oral bioavailability, and increase the half-life and solubility of said lipid-regulating agent.
The invention will be understood more clearly from the following non-limiting representative examples:
Example 1
SR Soybean oil (24.33 g) was added to a beaker and fenofibrate (0.67 g) was dissolved in it by stirring. Sorbitan monooleate (2.5 g) was added to the beaker and mixed until uniform. Polysorbate 80 (0.5 g) was then added and mixed until uniform. Finally water (72 g) was added slowly with constant mixing until a uniform emulsion resulted. Example 2
SR Soybean oil (24 g) is added to a beaker and pravastatin (1 g) is dispersed in it by stirring. Sorbitan monooleate (2.5 g) is added to the beaker and mixed until uniform. Polysorbate 80 (0.5 g) is then added and mixed until uniform. Finally water (72 g) is added slowly with constant mixing until a uniform emulsion resulted.
Example 3
SR Soybean oil (24 g) is added to a beaker and atorvastatin (1 g) is dispersed in it by stirring. Sorbitan monooleate (2.5 g) is added to the beaker and mixed until uniform. Polysorbate 80 (0.5 g) is then added and mixed until uniform. Finally water (72 g) is added slowly with constant mixing until a uniform emulsion resulted.
Example 4
The emulsion prepared by the process described in Example 1, and from a commercial fenofibrate composition, Lipanthyl 67M (Groupe Fournier) (Reference) , were administered to a group of dogs at a dose of 67 mg fenofibrate/dog (10 mL emulsion or one capsule/dog) . The plasma concentrations of fenofibric acid were determined by HPLC. Concentrations were normalized to a 6.7 mg/kg dose in each dog. Figure 1 presents the resulting data in graph form. The results provided as mean ± SD, n=6, were as follows : Lipanthyl 67M (Reference) : Cmax = 1.88 ± 0.97 mcg/ml Tmax = 1.6 ± 0.9 hr
Figure imgf000010_0001
AUC (0-24) = 11.08 ± 9.42 mcg*hr/ml
Emulsion of Example 1 : Cmax = 4.97 ± 3.13 mcg/ml Tmax = 1.1 ± 0.5 hr
Figure imgf000010_0002
AUC (0-24) = 24.21 ± 11.69 mcg*»hr/ml AUC relative to Reference = 2.2

Claims

Claims
1. A composition comprising a lipid-regulating agent dissolved or dispersed in at least one oil with one or more emulsifiers, wherein the mixture is capable of forming an emulsion upon dilution with an aqueous phase .
2. A composition of claim 1 wherein said lipid-regulating agent is a fibrate.
3. A composition of claim 2 wherein said fibrate is fenofibrate .
4. A composition of claim 1 wherein said lipid-regulating agent is a statin.
5. A composition of claim 4 wherein said statin is pravastatin.
6. A composition of claim 4 wherein said statin is atorvastatin.
7. A composition of claim 1 wherein at least one or more of said emulsifiers is selected from phospholipids, polyoxyethylene sorbitan fatty acid derivatives, sorbitan fatty acid derivatives, Polyoxyl-35-castor oil (Cremophor EL, available from BASF) , castor oil or hydrogenated castor oil ethoxylates, polyglycerol esters of fatty acids, fatty acid ethoxylates, alcohol ethoxylates, polyoxyethylene-polyoxypropylene co- polymers and block co-polymers, and TPGS (d-alpha tocopheryl polyethylene glycol 1000 succinate) .
8. A composition of claim 7 wherein at least one or more of said emulsifiers is polyoxyethylene sorbitan fatty acid derivatives, sorbitan fatty acid derivatives and polyoxyl-35-castor oil.
9. A composition of claim 1 wherein said oil is selected from soybean oil, coconut oil, canola oil, corn oil, palm kernel oil, cottonseed oil, olive oil, peanut oil, safflower oil and sesame oil.
10. A composition of claim 9 wherein said oil is soybean oil.
11. A composition of claim 1 further comprising a co- solvent .
12. A composition of claim 11 wherein said co-solvent is ethanol, propylene glycol or polyethylene glycol.
13. A delivery system comprising a composition of claim 1.
14. A delivery system of claim 13 wherein said delivery system is an emulsion.
15. A delivery system of claim 13 wherein said delivery system is a capsule.
16. A method of treating hyperlipidemia comprising the administration of a composition of claim 1 to a patient .
17. A method of treating hyperlipidemia comprising the administration of a composition of claim 3 to a patient .
18. A method of treating hyperlipidemia comprising the administration of a composition of claim 14 to a patient .
PCT/US2000/007650 1999-03-31 2000-03-23 Novel formulations comprising lipid-regulating agents WO2000057859A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CA002365128A CA2365128A1 (en) 1999-03-31 2000-03-23 Novel formulations comprising lipid-regulating agents
AU40211/00A AU4021100A (en) 1999-03-31 2000-03-23 Novel formulations comprising lipid-regulating agents
JP2000607610A JP2003520767A (en) 1999-03-31 2000-03-23 Novel formulation containing lipid regulator
EP00919545A EP1162954A1 (en) 1999-03-31 2000-03-23 Novel formulations comprising lipid-regulating agents
MXPA01009840A MXPA01009840A (en) 1999-03-31 2000-03-23 Novel formulations comprising lipid-regulating agents.
HK02104038.4A HK1043936A1 (en) 1999-03-31 2002-05-30 Novel formulations comprising lipid-regulating agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US28251399A 1999-03-31 1999-03-31
US09/282,513 1999-03-31

Publications (1)

Publication Number Publication Date
WO2000057859A1 true WO2000057859A1 (en) 2000-10-05

Family

ID=23081844

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/007650 WO2000057859A1 (en) 1999-03-31 2000-03-23 Novel formulations comprising lipid-regulating agents

Country Status (7)

Country Link
EP (1) EP1162954A1 (en)
JP (1) JP2003520767A (en)
AU (1) AU4021100A (en)
CA (1) CA2365128A1 (en)
HK (1) HK1043936A1 (en)
MX (1) MXPA01009840A (en)
WO (1) WO2000057859A1 (en)

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1185252A1 (en) * 1999-06-11 2002-03-13 Abbott Laboratories Novel formulations comprising lipid-regulating agents
WO2002039983A2 (en) * 2000-11-17 2002-05-23 Lipocine, Inc. Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
WO2002100394A1 (en) * 2001-06-12 2002-12-19 Galephar M/F Oral pharmaceutical composition containing a statin derivative
WO2006045865A1 (en) 2004-10-19 2006-05-04 Gp Pharm S.A. Pharmaceutical formulation comprising microcapusles of statins suspended in alkyl esters of polyunsaturated fatty acids (pufa)
EP1922065A2 (en) * 2005-08-04 2008-05-21 Transform Pharmaceuticals, Inc. Novel formulations comprising fenofibrate and a statin, and related methods of treatment
US7927627B2 (en) 2002-05-24 2011-04-19 Elan Pharma International, Ltd. Nanoparticulate fibrate formulations
EP2400840A1 (en) * 2009-02-24 2012-01-04 Madeira Therapeutics Liquid statin formulations
CN103110594A (en) * 2013-02-02 2013-05-22 台州职业技术学院 Atorvastatin calcium nano freeze-dried powder and preparation method thereof
US8865695B2 (en) 2009-01-08 2014-10-21 Lipocine Inc. Steroidal compositions
US9034858B2 (en) 2010-11-30 2015-05-19 Lipocine Inc. High-strength testosterone undecanoate compositions
WO2015185240A1 (en) 2014-06-04 2015-12-10 Sigma-Tau Industrire Farmaceutiche Riunite S.P.A. Compositions containing simvastatin in omega-3 polyunsaturated fatty acids
US9265742B2 (en) 2010-10-29 2016-02-23 Infirst Healthcare Limited Compositions and methods for treating inflammatory pain
US9271950B2 (en) 2010-10-29 2016-03-01 Infirst Healthcare Limited Compositions for treating chronic inflammation and inflammatory diseases
US9308213B2 (en) 2010-10-29 2016-04-12 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9358241B2 (en) 2010-11-30 2016-06-07 Lipocine Inc. High-strength testosterone undecanoate compositions
US9498485B2 (en) 2014-08-28 2016-11-22 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US9504664B2 (en) 2010-10-29 2016-11-29 Infirst Healthcare Limited Compositions and methods for treating severe pain
US9737500B2 (en) 2010-10-29 2017-08-22 Infirst Healthcare Limited Compositions and methods for treating severe pain
US9744132B2 (en) 2010-10-29 2017-08-29 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
RU2635188C2 (en) * 2011-02-04 2017-11-09 ИнФёрст Хэлткэр Лимитед Compositions and methods for treatment of chronic inflammation and inflammatory diseases
US10561615B2 (en) 2010-12-10 2020-02-18 Lipocine Inc. Testosterone undecanoate compositions
US10695432B2 (en) 2010-10-29 2020-06-30 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US10695431B2 (en) 2010-10-29 2020-06-30 Infirst Healthcare Limited Solid solution compositions and use in cardiovascular disease
US11202831B2 (en) 2010-10-29 2021-12-21 Infirst Healthcare Limited Solid solution compositions and use in cardiovascular disease
US11224659B2 (en) 2010-10-29 2022-01-18 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US11559530B2 (en) 2016-11-28 2023-01-24 Lipocine Inc. Oral testosterone undecanoate therapy
US11707467B2 (en) 2014-08-28 2023-07-25 Lipocine Inc. (17-ß)-3-oxoandrost-4-en-17YL tridecanoate compositions and methods of their preparation and use
US11730709B2 (en) 2010-10-29 2023-08-22 Infirst Healthcare Limited Compositions and methods for treating severe pain

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1590864A (en) * 1978-05-16 1981-06-10 Lilly Industries Ltd Thixotropic filling medium for hard gelatin capsules
EP0031603A1 (en) * 1979-12-31 1981-07-08 American Cyanamid Company Pharmaceutical composition of matter
US4946866A (en) * 1985-08-02 1990-08-07 Byk Gulden Lomberg Chemische Fabrik Gmbh Use of oxirancarboxylic acids for the treatment of hyperlipemia
EP0700678A1 (en) * 1994-07-13 1996-03-13 Wakamoto Pharmaceutical Co., Ltd. Stable lipid emulsion
US5645856A (en) * 1994-03-16 1997-07-08 R. P. Scherer Corporation Delivery systems for hydrophobic drugs
WO1999029300A1 (en) * 1997-12-10 1999-06-17 Rtp Pharma Inc. Self-emulsifying fenofibrate formulations

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1590864A (en) * 1978-05-16 1981-06-10 Lilly Industries Ltd Thixotropic filling medium for hard gelatin capsules
EP0031603A1 (en) * 1979-12-31 1981-07-08 American Cyanamid Company Pharmaceutical composition of matter
US4946866A (en) * 1985-08-02 1990-08-07 Byk Gulden Lomberg Chemische Fabrik Gmbh Use of oxirancarboxylic acids for the treatment of hyperlipemia
US5645856A (en) * 1994-03-16 1997-07-08 R. P. Scherer Corporation Delivery systems for hydrophobic drugs
EP0700678A1 (en) * 1994-07-13 1996-03-13 Wakamoto Pharmaceutical Co., Ltd. Stable lipid emulsion
WO1999029300A1 (en) * 1997-12-10 1999-06-17 Rtp Pharma Inc. Self-emulsifying fenofibrate formulations

Cited By (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1185252A1 (en) * 1999-06-11 2002-03-13 Abbott Laboratories Novel formulations comprising lipid-regulating agents
WO2002039983A2 (en) * 2000-11-17 2002-05-23 Lipocine, Inc. Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
WO2002039983A3 (en) * 2000-11-17 2002-10-10 Lipocine Inc Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US6982281B1 (en) 2000-11-17 2006-01-03 Lipocine Inc Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
WO2002100394A1 (en) * 2001-06-12 2002-12-19 Galephar M/F Oral pharmaceutical composition containing a statin derivative
US7931917B2 (en) 2002-05-24 2011-04-26 Elan Pharma International, Ltd. Nanoparticulate fibrate formulations
US7927627B2 (en) 2002-05-24 2011-04-19 Elan Pharma International, Ltd. Nanoparticulate fibrate formulations
WO2006045865A1 (en) 2004-10-19 2006-05-04 Gp Pharm S.A. Pharmaceutical formulation comprising microcapusles of statins suspended in alkyl esters of polyunsaturated fatty acids (pufa)
US7772277B2 (en) 2005-08-04 2010-08-10 Transform Pharmaceuticals, Inc. Formulations comprising fenofibrate and a statin, and related methods of treatment
EP1922065A4 (en) * 2005-08-04 2009-11-11 Transform Pharmaceuticals Inc Novel formulations comprising fenofibrate and a statin, and related methods of treatment
EP1922065A2 (en) * 2005-08-04 2008-05-21 Transform Pharmaceuticals, Inc. Novel formulations comprising fenofibrate and a statin, and related methods of treatment
US11304960B2 (en) 2009-01-08 2022-04-19 Chandrashekar Giliyar Steroidal compositions
US8865695B2 (en) 2009-01-08 2014-10-21 Lipocine Inc. Steroidal compositions
US11052096B2 (en) 2009-01-08 2021-07-06 Lipocine Inc. Steroidal compositions
EP2400840A1 (en) * 2009-02-24 2012-01-04 Madeira Therapeutics Liquid statin formulations
EP2400840A4 (en) * 2009-02-24 2012-08-01 Madeira Therapeutics Liquid statin formulations
US10849869B2 (en) 2010-10-29 2020-12-01 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US11065218B2 (en) 2010-10-29 2021-07-20 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US9265742B2 (en) 2010-10-29 2016-02-23 Infirst Healthcare Limited Compositions and methods for treating inflammatory pain
US9271950B2 (en) 2010-10-29 2016-03-01 Infirst Healthcare Limited Compositions for treating chronic inflammation and inflammatory diseases
US9308213B2 (en) 2010-10-29 2016-04-12 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9326958B2 (en) 2010-10-29 2016-05-03 Infirst Healthcare Limited Compositions for treating chronic inflammation and inflammatory diseases
US11918654B2 (en) 2010-10-29 2024-03-05 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US9381180B2 (en) 2010-10-29 2016-07-05 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US9427422B2 (en) 2010-10-29 2016-08-30 Infirst Healthcare Limited Compositions for treating cardiovascular diseases
US11844773B2 (en) 2010-10-29 2023-12-19 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US11826428B2 (en) 2010-10-29 2023-11-28 Infirst Healthcare Limited Solid solution compositions comprising cannabidiols
US9504664B2 (en) 2010-10-29 2016-11-29 Infirst Healthcare Limited Compositions and methods for treating severe pain
US9693980B2 (en) 2010-10-29 2017-07-04 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US9737500B2 (en) 2010-10-29 2017-08-22 Infirst Healthcare Limited Compositions and methods for treating severe pain
US9744132B2 (en) 2010-10-29 2017-08-29 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9750810B2 (en) 2010-10-29 2017-09-05 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US11730709B2 (en) 2010-10-29 2023-08-22 Infirst Healthcare Limited Compositions and methods for treating severe pain
US11660276B2 (en) 2010-10-29 2023-05-30 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US9775820B2 (en) 2010-10-29 2017-10-03 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9789075B2 (en) 2010-10-29 2017-10-17 Infirst Helathcare Limited Compositions and methods for treating cardiovascular diseases
US9795577B2 (en) 2010-10-29 2017-10-24 Infirst Healthcare Limited Compositions and methods for treating severe pain
US11224659B2 (en) 2010-10-29 2022-01-18 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US9820952B2 (en) 2010-10-29 2017-11-21 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9827215B2 (en) 2010-10-29 2017-11-28 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US11202831B2 (en) 2010-10-29 2021-12-21 Infirst Healthcare Limited Solid solution compositions and use in cardiovascular disease
US11154500B2 (en) 2010-10-29 2021-10-26 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10004704B2 (en) 2010-10-29 2018-06-26 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US10143671B2 (en) 2010-10-29 2018-12-04 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10155042B2 (en) 2010-10-29 2018-12-18 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US10154975B2 (en) 2010-10-29 2018-12-18 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10188619B2 (en) 2010-10-29 2019-01-29 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10213381B2 (en) 2010-10-29 2019-02-26 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US11103472B2 (en) 2010-10-29 2021-08-31 Infirst Healthcare Limited Oral suspensions comprising a non-steroidal anti-inflammatory drug (NSAID)
US10231943B2 (en) 2010-10-29 2019-03-19 Infirst Healthcare Limited Compositions and methods for treating cardiovascular diseases
US10363232B2 (en) 2010-10-29 2019-07-30 Infirst Healthcare Limited Compositions and methods for treating severe pain
US10426748B2 (en) 2010-10-29 2019-10-01 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US11000493B2 (en) 2010-10-29 2021-05-11 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10588878B2 (en) 2010-10-29 2020-03-17 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10596132B2 (en) 2010-10-29 2020-03-24 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US10653778B2 (en) 2010-10-29 2020-05-19 Infirst Healthcare Limited Compositions and methods for treating chronic inflammation and inflammatory diseases
US10695432B2 (en) 2010-10-29 2020-06-30 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US10695431B2 (en) 2010-10-29 2020-06-30 Infirst Healthcare Limited Solid solution compositions and use in cardiovascular disease
US10857114B2 (en) 2010-10-29 2020-12-08 Infirst Healthcare Limited Compositions and methods for treating severe pain
US10835490B2 (en) 2010-10-29 2020-11-17 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9757390B2 (en) 2010-11-30 2017-09-12 Lipocine Inc. High-strength testosterone undecanoate compositions
US9205057B2 (en) 2010-11-30 2015-12-08 Lipocine Inc. High-strength testosterone undecanoate compositions
US10716794B2 (en) 2010-11-30 2020-07-21 Lipocine Inc. High-strength testosterone undecanoate compositions
US10973833B2 (en) 2010-11-30 2021-04-13 Lipocine Inc. High-strength testosterone undecanoate compositions
US9034858B2 (en) 2010-11-30 2015-05-19 Lipocine Inc. High-strength testosterone undecanoate compositions
US9358241B2 (en) 2010-11-30 2016-06-07 Lipocine Inc. High-strength testosterone undecanoate compositions
US10226473B2 (en) 2010-11-30 2019-03-12 Lipocine Inc. High-strength testosterone undecanoate compositions
US9949985B2 (en) 2010-11-30 2018-04-24 Lipocine Inc. High-strength testosterone undecanoate compositions
US9943527B2 (en) 2010-11-30 2018-04-17 Lipocine Inc. High-strength testosterone undecanoate compositions
US10799513B2 (en) 2010-11-30 2020-10-13 Lipocine Inc. High-strength testosterone undecanoate compositions
US9480690B2 (en) 2010-11-30 2016-11-01 Lipocine Inc. High-strength testosterone undecanoate compositions
US10561615B2 (en) 2010-12-10 2020-02-18 Lipocine Inc. Testosterone undecanoate compositions
RU2635188C2 (en) * 2011-02-04 2017-11-09 ИнФёрст Хэлткэр Лимитед Compositions and methods for treatment of chronic inflammation and inflammatory diseases
CN103110594A (en) * 2013-02-02 2013-05-22 台州职业技术学院 Atorvastatin calcium nano freeze-dried powder and preparation method thereof
WO2015185240A1 (en) 2014-06-04 2015-12-10 Sigma-Tau Industrire Farmaceutiche Riunite S.P.A. Compositions containing simvastatin in omega-3 polyunsaturated fatty acids
US11707467B2 (en) 2014-08-28 2023-07-25 Lipocine Inc. (17-ß)-3-oxoandrost-4-en-17YL tridecanoate compositions and methods of their preparation and use
US9757389B2 (en) 2014-08-28 2017-09-12 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US9498485B2 (en) 2014-08-28 2016-11-22 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US11298365B2 (en) 2014-08-28 2022-04-12 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US11872235B1 (en) 2014-08-28 2024-01-16 Lipocine Inc. Bioavailable solid state (17-β)-Hydroxy-4-Androsten-3-one esters
US11559530B2 (en) 2016-11-28 2023-01-24 Lipocine Inc. Oral testosterone undecanoate therapy

Also Published As

Publication number Publication date
CA2365128A1 (en) 2000-10-05
EP1162954A1 (en) 2001-12-19
JP2003520767A (en) 2003-07-08
HK1043936A1 (en) 2002-10-04
AU4021100A (en) 2000-10-16
MXPA01009840A (en) 2002-06-21

Similar Documents

Publication Publication Date Title
US6372251B2 (en) Formulations comprising lipid-regulating agents
EP1162954A1 (en) Novel formulations comprising lipid-regulating agents
US6465011B2 (en) Formulations comprising lipid-regulating agents
EP1140036A2 (en) Novel formulations comprising lipid-regulating agents
CA2367995A1 (en) Novel formulations comprising lipid-regulating agents
US20020102301A1 (en) Pharmaceutical solid self-emulsifying composition for sustained delivery of biologically active compounds and the process for preparation thereof
US6838091B2 (en) Formulations comprising lipid-regulating agents
US20070009559A1 (en) Free-flowing solid formulations with improved bio-availability of poorly water soluble drugs and process for making the same
NZ552390A (en) Novel fenofibrate formulations and related methods of treatment
US6719999B2 (en) Formulations comprising lipid-regulating agents
WO2002100394A1 (en) Oral pharmaceutical composition containing a statin derivative
US6814977B1 (en) Formulations comprising lipid-regulating agents
US20020040046A1 (en) Novel formulations comprising lipid-regulating agents
CA3072559A1 (en) Pharmaceutical composition
JP2001523718A (en) Formulations containing dissolved paroxetine
US7014864B1 (en) Formulations comprising lipid-regulating agents
EP1183017A1 (en) Novel formulations comprising lipid-regulating agents
WO2024033521A1 (en) Oral solid dosage forms comprising cannabinoids
MXPA06005247A (en) Pharmaceutical composition for oral administration of a pyrazol-3-carboxamide derivative

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2365128

Country of ref document: CA

Ref country code: CA

Ref document number: 2365128

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 2000919545

Country of ref document: EP

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 607610

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: PA/a/2001/009840

Country of ref document: MX

WWP Wipo information: published in national office

Ref document number: 2000919545

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000919545

Country of ref document: EP