WO2015186040A1 - Composition de nanoémulsion stable - Google Patents

Composition de nanoémulsion stable Download PDF

Info

Publication number
WO2015186040A1
WO2015186040A1 PCT/IB2015/054092 IB2015054092W WO2015186040A1 WO 2015186040 A1 WO2015186040 A1 WO 2015186040A1 IB 2015054092 W IB2015054092 W IB 2015054092W WO 2015186040 A1 WO2015186040 A1 WO 2015186040A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition according
nanoemulsion
composition
polysorbate
mixtures
Prior art date
Application number
PCT/IB2015/054092
Other languages
English (en)
Inventor
Rajesh Rao
Anuj Kumar Fanda
Satish Kumar Jain
Romi Barat Singh
Original Assignee
Sun Pharmaceutical Industries Limited
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 Sun Pharmaceutical Industries Limited filed Critical Sun Pharmaceutical Industries Limited
Publication of WO2015186040A1 publication Critical patent/WO2015186040A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A61K8/062—Oil-in-water emulsions
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • 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
    • A61K47/26—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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4993—Derivatives containing from 2 to 10 oxyalkylene groups
    • 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
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/21—Emulsions characterized by droplet sizes below 1 micron
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/26—Optical properties
    • A61K2800/262—Transparent; Translucent

Definitions

  • the present invention relates to a thermodynamically and kinetically stable clear nanoemulsion composition
  • a thermodynamically and kinetically stable clear nanoemulsion composition comprising a surfactant in an amount of less than about 10% w/w of the total composition, and a process for its preparation.
  • Nanoemulsions are emulsion systems of oil, water, surfactants, and optionally co- solvents, with a droplet size in the range of about 5 nm to about 500 nm. Usually, the average droplet size is between 20 nm and 200 nm. Nanoemulsions are also referred to as mini-emulsions, ultrafine emulsions, and sub-micron emulsions. Nanoemulsions have found wide applications in drug delivery of poorly soluble active agents. They enhance solubility, resulting in improved bioavailability of the active agents.
  • Nanoemulsions with a small droplet size have an added benefit of being translucent or even transparent. But droplet size may increase over time due to coalescence, flocculation, and/or Ostwald ripening. The small size of droplets of nanoemulsions makes them particularly prone to Ostwald ripening. An increase in droplet size over time is disadvantageous as the emulsion will lose its clarity. To overcome this problem, the nanoemulsions contain relatively higher amounts of surfactants to stabilize the nano-droplets.
  • nanoemulsion compositions of dorzolamide for ophthalmic use contain more than 12% w/w of the surfactant.
  • Ophthalmic dosage forms contain relatively lesser amounts of active agent and thus, the amount of active agent that needs to be loaded in a nanoemulsion for ophthalmic use is relatively lower.
  • these nanoemulsions when subjected to freeze-thaw cycle test and stored at -21°C, turned turbid and the coagulation of internal phase at low temperature may be responsible for the instability.
  • PCT Publication No. WO 2009/067734 discloses a nanoemulsion comprising long chain triglycerides having a chain length of 12 carbon atoms or greater. This patent publication discloses that when medium chain triglycerides were used as the oil phase, high clarity nanoemulsions were obtained. However, these nanoemulsions were prone to Ostwald ripening and droplet size increased such that the nanoemulsion lost its clarity.
  • the present invention provides a clear nanoemulsion composition
  • a clear nanoemulsion composition comprising a medium-chain or a short-chain glyceride or mixtures thereof as an oily phase; and a surfactant in an amount of less than about 10% w/w of the total composition, wherein said composition is thermodynamically and kinetically stable.
  • compositions with high concentrations of surfactants may be poor in cases where chronic administration is intended.
  • Chronic oral administration of compositions with high concentrations of surfactant may lead to adverse effects such as diarrhea.
  • Topical administration of such compositions can cause irritation to the skin and mucosal membranes.
  • high concentrations of surfactant may cause lysis of human red blood cells.
  • the WHO and the US FDA have placed restrictions on the daily intake of many of the commonly used surfactants.
  • developing a stable nanoemulsion with a low concentration of surfactants presents significant challenges to the formulation scientists.
  • the present invention provides a thermodynamically and kinetically stable clear nanoemulsion composition
  • a thermodynamically and kinetically stable clear nanoemulsion composition comprising medium-chain or a short-chain glyceride or mixtures thereof as an oily phase, and a low amount of surfactant, particularly less than about 10% w/w of the total composition.
  • the advantages of using medium-chain or a short-chain glyceride over a long chain glyceride is that they are easy to emulsify and yield high clarity nanoemulsions.
  • a first aspect of the present invention provides a clear nanoemulsion composition comprising:
  • an active ingredient b) an oily phase selected from the group consisting of a medium-chain or a short- chain glyceride or mixtures thereof;
  • the surfactant is present in an amount of less than about 10% w/w of the total composition, and said composition is thermodynamically and kinetically stable.
  • the oily phase of the nanoemulsion composition of the present invention comprises either a medium-chain glyceride, a short-chain glyceride, or mixtures thereof.
  • the oily phase is present in an amount of about 5% w/w to about 25% w/w of the total composition.
  • medium-chain glyceride refers to mono-, di-, or triglycerides or polyoxylglycerides of fatty acids with a chain length of 8 to 12 carbon atoms.
  • the medium-chain glyceride is, for example, and without limitation fractionated coconut oil or palm seed oil; glycerides of caprylic/capric acid, e.g., Miglyol ® , Captex ® , tricaprylin, Labrafac TM Lipophile, Imwitor ® , akoline, Labrasol ® , and Sefsol TM ; glycerides of lauric acid, e.g., Gelucire ® 44/14; or mixtures thereof.
  • short-chain glyceride refers to mono-, di-, or triglycerides or polyoxylglycerides of fatty acids with a chain length of 1 to 7 carbons atoms.
  • the short-chain glyceride is, for example, and without limitation, triacetin, tripropionin, tributyrin, trihexanoin, triheptanoin, or mixtures thereof.
  • the short-chain glyceride is triacetin.
  • Surfactants are the agents that decrease the interfacial tension between two liquids, or between a liquid and a solid, thus allowing an easier spreading.
  • Surfactants may be anionic, cationic, or non-ionic, more particularly surfactants of HLB value of more than 10.
  • the surfactant is, for example, and without limitation, polysorbates, e.g., polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate 80; polyethylene glycol alkyl ethers; sugar esters, e.g., sucrose palmitate, sucrose laurate, sucrose distearate and monostearate (Crodesta Fl 10), sucrose monostearate (Crodesta F160), and saccharose monolaurate; polyethoxylated fatty acids; polyoxyethylene-polyoxypropylene block copolymers also known as 'poloxamers' available under various trade names, e.g., Synperonic® PE series, Pluronic® series, Lutrol®, Pluracare®, and Plurodac; polyethylene glycol alkyl phenol ethers; citric acid esters of monoglycerides; polyglycerol esters;
  • the surfactant is a non-ionic surfactant, more particularly the non-ionic surfactant is polysorbate 80.
  • Non-ionic surfactants are relatively less toxic than their ionic counterparts and have lower critical micelle concentrations.
  • the non-ionic surfactant is present in an amount of less than about 10% w/w of the total composition, in particular from about 5% w/w to less than about 10% w/w of the total composition.
  • co-solvent refers to the agents that act synergistically with surfactants to facilitate in the dispersion process.
  • the co-solvent is, for example, and without limitation, Ci-Cio alcohols, e.g., methanol, ethanol, propanol, iso-propyl alcohol, butanol, pentanol, hexanol, heptanol, octanol, nonanol, and decanol; polyols, e.g., glycerol, propylene glycol, polyethylene glycol, and polypropylene glycol; diethylene glycol monoethyl ethers (Transcutol®); or mixtures thereof.
  • Ci-Cio alcohols e.g., methanol, ethanol, propanol, iso-propyl alcohol, butanol, pentanol, hexanol, heptanol, octanol, nonano
  • the co-solvent is propylene glycol.
  • the co-solvent is present in an amount of about 20% w/w to about 60% w/w of the total composition.
  • the ratio of surfactant to co-solvent in nanoemulsion composition of the present invention is between 1 :2 and 1 :6, in particular the ratio is 1 :3 to 1 :5.
  • the aqueous phase of the nanoemulsion composition of the present invention comprises purified or ultrapure water, saline, or buffered saline.
  • the amount of aqueous phase in the nanoemulsion may be from about 30% w/w to about 70% w/w of the total composition.
  • the term "clear nanoemulsion” as used herein refers to the nanoemulsions that are transparent and are visually clear with no signs of turbidity. Further, upon infinite dilution with an aqueous phase, they form true solutions.
  • the average globule size of the nanoemulsion composition of the present invention is from about 5 nm to about 200 nm, in particular the average globule size is from about 5 nm to about 100 nm.
  • Average globule size refers to Z-average globule size.
  • the Z-average globule size is the mean diameter based on the intensity of light scattered, as determined using a Nanosizer or Zetasizer, based on the principle of dynamic light scattering.
  • Thermodynamically stable refers to nanoemulsions showing no signs of phase separation, creaming, or cracking when subjected to extreme temperature. At low temperature values of less than 10°C, in particular between 0°C and -21°C the oily phase is rejected leading to phase separation and instability. High temperature values of equal to or more than 40°C result in isotropic clear solutions.
  • “Kinetically stable” refers to nanoemulsions showing no signs of coalescence, flocculation, and/or Ostwald ripening over a period of time.
  • the medium-chain glyceride is, for example, and without limitation, fractionated coconut oil or palm seed oil, glycerides of caprylic/capric acid, glycerides of lauric acid, or mixtures thereof.
  • the short-chain glyceride is, for example, and without limitation, triacetin, tripropionin, tributyrin, trihexanoin, triheptanoin, or mixtures thereof.
  • the short-chain glyceride is triacetin.
  • the surfactant is a non-ionic surfactant.
  • the non-ionic surfactant is, for example, and without limitation, polysorbates, polyethylene glycol alkyl ethers, sugar esters, polyethoxylated fatty acids, polyoxyethylene-polyoxypropylene block co-polymers, polyethylene glycol alkyl phenol ethers, citric acid esters of monoglycerides, polyglycerol esters, polyethoxylated fatty acid diesters, sorbitan fatty acid esters, PEG-fatty acid mono and diesters, polyethylene glycol glycerol fatty acid esters, alcohol oil trans-esters, or mixtures thereof.
  • the non-ionic surfactant is polysorbate, for example, and without limitation, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or mixtures thereof.
  • the non-ionic surfactant is polysorbate 80.
  • the co-solvent is, for example, and without limitation, Ci-Cio alcohol, polyols, diethylene glycol monoethyl ether, or mixtures thereof.
  • the co-solvent is a polyol.
  • the polyol is propylene glycol.
  • the average globule size is from about 5 nm to about 200 nm.
  • the average globule size is from about 5 nm to about 100 nm.
  • composition is prepared by a simple mixing process comprising:
  • step ii) adding an active ingredient to the nanoemulsion of step i) followed by mixing to obtain an active ingredient-loaded nanoemulsion.
  • a second aspect of the present invention provides a clear nanoemulsion composition comprising:
  • polysorbate 80 in an amount of about 5% to less than about 10%
  • composition is thermodynamically and kinetically stable.
  • triacetin is present in an amount of about 5% w/w to about 25% w/w of the total composition.
  • propylene glycol is present in an amount of about 20% w/w to about 60% w/w of the total composition.
  • water is present in an amount of about 30% w/w to about 70% w/w of the total composition.
  • the composition is prepared by a simple mixing process comprising:
  • step ii) adding an active ingredient to the nanoemulsion of step i) followed by mixing to obtain an active ingredient-loaded nanoemulsion.
  • compositions of the invention were subjected to heating-cooling cycles, freeze-thaw cycles, and dispersibility tests:
  • Heating-cooling cycle The compositions were exposed to six cycles between refrigerator temperature (4°C) and 40°C, with storage at each temperature for not less than 48 hours, followed by visual examination of the compositions for signs of phase separation.
  • Freeze-thaw cycle The compositions were exposed to three freeze-thaw cycles between -21°C and 25°C, with storage at each temperature for not less than 48 hours, followed by visual examination of the compositions for signs of phase separation.
  • Dispersibility test One mL of each composition was added to 500 mL of water in a dissolution assembly maintained at 37°C ⁇ 0.5°C, followed by visual examination of the compositions for signs of phase separation and transparency. On infinite dilution of nanoemulsion composition, there is a high possibility of phase separation leading to precipitation of the active ingredient. This process is thermodynamically driven by the requirement of the surfactant to maintain an aqueous phase concentration equivalent to its critical micelle concentration (CMC).
  • CMC critical micelle concentration
  • compositions of the present invention were kept in closed vials at room temperature for at least one month, followed by visual examination of the compositions for turbidity or loss of clarity.
  • any suitable active ingredient can be incorporated into the nanoemulsion composition of the present invention.
  • active ingredients include, but are not limited to, hormones, e.g., insulin, calcitonin, somatropin, somatotropin, somastostatin, insulin-like growth factor, luteinizing hormone releasing hormone, growth hormones, growth hormone releasing hormone, sex hormones, parathyroid hormone, and calcitonin; hematological agents; anticoagulants; hematopoietic agents; hemostatics; thrombolytic agents; endocrine agents; anti-diabetic agents; anti-thyroid agents; beta-adrenoceptor blocking agents; biphosphonates; uterine-active agents; cardiovascular agents; antiarrhythmic agents; anti-anginal agents; anti-hypertensive agents; vasodilators; agents used in treatment of heart disorders; cardiac inotropic agents; renal agents; genitourinary agents; antidiuretic agents; respiratory agents; antihistamines;
  • parasympathomimetics sympathomimetics; xanthines; central nervous system agents; analgesics; anesthetics; anti-emetic agents; anorexiants; anti-depressants; anti-migraine agents; anti-epileptics; dopaminergics; anti-cholinergics; anti-parkinsonian agents; muscle relaxants; narcotic antagonists; sedatives; stimulants; treatments for attention deficit disorder; immunosuppressive agents; gastrointestinal agents; systemic anti -infectives; agents used in the treatment of AIDS; anti-helmintics; anti-mycobacterial agents;
  • the active ingredient is acitretin, isotretinoin, amiodarone, cefpodoxime proxetil, atorvastatin, azithromycin, carvedilol, cyclosporine, or digoxin.
  • the amount of active ingredient that can be loaded into the nanoemulsion of present invention is from about 0.05% w/w to about 20% w/w of the total composition, in particular from about 0.1% w/w to about 5% w/w of the total composition.
  • nanoemulsions of the present invention are suitable for administration via any of the well-known routes including oral, parenteral, ophthalmic, otic, and
  • the nanoemulsion of the present invention may further contain additives, e.g., stabilizers, antioxidants, preservatives, buffering agents, charge inducing agents, polymers, and proteins.
  • additives e.g., stabilizers, antioxidants, preservatives, buffering agents, charge inducing agents, polymers, and proteins.
  • Stabilizers can be anti -creaming or anti -foaming agents or any other agents which impart stability to the nanoemulsion.
  • Triacetin, polysorbate 80, and propylene glycol were mixed with water using a blender to obtain a clear nanoemulsion.
  • nanoemulsion compositions prepared according to Examples 1-7 were subjected to heating-cooling cycles, freeze-thaw cycles, and dispersibility tests. All of the nanoemulsion compositions were found to be thermodynamically stable with no phase separation, creaming, or cracking.
  • nanoemulsion compositions prepared according to Examples 1-7 were kept in closed vials at room temperature for a period of one month and were visually examined for turbidity or loss of clarity. All of the nanoemulsion compositions were found to be kinetically stable showing no signs of coalescence, flocculation, or Ostwald ripening.
  • the globule size of nanoemulsion of Example 6 was measured using Zetasizer.
  • the average globule size (Z-average globule size) was found out to be 11.93 nm.
  • a suitable active agent was added to the nanoemulsion of Example 6 and mixed to obtain an active ingredient-loaded nanoemulsion.
  • Ten mg of cefpodoxime proxetil was dissolved in one g of the nanoemulsion to yield a clear active-ingredient loaded nanoemulsion.

Abstract

La présente invention concerne une composition de nanoémulsion transparente cinétiquement et thermodynamiquement stable, comprenant un tensioactif dans une quantité inférieure à environ 10 % en poids de la composition totale, et un procédé pour sa préparation. Des tensioactifs dans une concentration élevée irritent la muqueuse. La tolérabilité de compositions ayant des quantités élevées de tensioactifs peut être médiocre dans des cas où une administration chronique est voulue. L'administration orale chronique de compositions ayant des concentrations élevées de tensioactif peut entraîner des effets indésirables tels que la diarrhée.
PCT/IB2015/054092 2014-06-02 2015-05-29 Composition de nanoémulsion stable WO2015186040A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1457/DEL/2014 2014-06-02
IN1457DE2014 2014-06-02

Publications (1)

Publication Number Publication Date
WO2015186040A1 true WO2015186040A1 (fr) 2015-12-10

Family

ID=54766228

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2015/054092 WO2015186040A1 (fr) 2014-06-02 2015-05-29 Composition de nanoémulsion stable

Country Status (1)

Country Link
WO (1) WO2015186040A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109771339A (zh) * 2019-03-13 2019-05-21 中国热带农业科学院椰子研究所 一种具有美白保湿功效的椰子油纳米乳液的制备方法
JP2021510676A (ja) * 2018-01-23 2021-04-30 ユニリーバー・ナームローゼ・ベンノートシヤープ ラウリン油を含む透明ナノエマルジョンの製造方法
JP2021511292A (ja) * 2018-01-23 2021-05-06 ユニリーバー・ナームローゼ・ベンノートシヤープ ラウリン油を含む透明ナノエマルジョン

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5698219A (en) * 1994-08-08 1997-12-16 Laboratorios Cusi, S.A. Nanoemulsion of the oil water type, useful as an ophthalmic vehicle and process for the preparation thereof
US20030087967A1 (en) * 2001-01-18 2003-05-08 Eric Quemin Translucent nanoemulsion, production method, and uses thereof in the cosmetic, dermatological and/or opthalmological fields
US20090208541A1 (en) * 2004-10-26 2009-08-20 Jean-Luc Gesztesi Oil-In-Water Nanoemulsion, A Cosmetic Composition And A Cosmetic Product Comprising It, A Process For Preparing Said Nanoemulsion
US20100305218A1 (en) * 2007-11-28 2010-12-02 Timothy James Wooster Nanoemulsions
US8357639B2 (en) * 2007-07-03 2013-01-22 Baker Hughes Incorporated Nanoemulsions
US8722131B2 (en) * 2010-09-07 2014-05-13 Dsm Nutritional Products Ag Comestible emulsions

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5698219A (en) * 1994-08-08 1997-12-16 Laboratorios Cusi, S.A. Nanoemulsion of the oil water type, useful as an ophthalmic vehicle and process for the preparation thereof
US20030087967A1 (en) * 2001-01-18 2003-05-08 Eric Quemin Translucent nanoemulsion, production method, and uses thereof in the cosmetic, dermatological and/or opthalmological fields
US20090208541A1 (en) * 2004-10-26 2009-08-20 Jean-Luc Gesztesi Oil-In-Water Nanoemulsion, A Cosmetic Composition And A Cosmetic Product Comprising It, A Process For Preparing Said Nanoemulsion
US8357639B2 (en) * 2007-07-03 2013-01-22 Baker Hughes Incorporated Nanoemulsions
US20100305218A1 (en) * 2007-11-28 2010-12-02 Timothy James Wooster Nanoemulsions
US8722131B2 (en) * 2010-09-07 2014-05-13 Dsm Nutritional Products Ag Comestible emulsions

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021510676A (ja) * 2018-01-23 2021-04-30 ユニリーバー・ナームローゼ・ベンノートシヤープ ラウリン油を含む透明ナノエマルジョンの製造方法
JP2021511292A (ja) * 2018-01-23 2021-05-06 ユニリーバー・ナームローゼ・ベンノートシヤープ ラウリン油を含む透明ナノエマルジョン
JP7266038B2 (ja) 2018-01-23 2023-04-27 ユニリーバー・アイピー・ホールディングス・ベスローテン・ヴェンノーツハップ ラウリン油を含む透明ナノエマルジョン
JP7309720B2 (ja) 2018-01-23 2023-07-18 ユニリーバー・アイピー・ホールディングス・ベスローテン・ヴェンノーツハップ ラウリン油を含む透明ナノエマルジョンの製造方法
CN109771339A (zh) * 2019-03-13 2019-05-21 中国热带农业科学院椰子研究所 一种具有美白保湿功效的椰子油纳米乳液的制备方法
CN109771339B (zh) * 2019-03-13 2021-07-30 中国热带农业科学院椰子研究所 一种具有美白保湿功效的椰子油纳米乳液的制备方法

Similar Documents

Publication Publication Date Title
JP7412105B2 (ja) ナノエマルジョン送達系の組成物
Sriamornsak et al. A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution
Patel et al. Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate
Shah et al. Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs
Makadia et al. Self-nano emulsifying drug delivery system (SNEDDS): future aspects
Weerapol et al. Self-nanoemulsifying drug delivery system of nifedipine: impact of hydrophilic–lipophilic balance and molecular structure of mixed surfactants
Spernath et al. Microemulsions as carriers for drugs and nutraceuticals
Patel et al. Self micro-emulsifying drug delivery system: formulation development and biopharmaceutical evaluation of lipophilic drugs
AU2016226224B2 (en) Self-emulsifying drug delivery system (SEDDS) for ophthalmic drug delivery
Jaiswal et al. Bioavailability enhancdement of poorly soluble drugs by smedds: a review
WO2015100234A1 (fr) Compositions de racécadotril
EP2866789A1 (fr) Compositions lipidiques de racécadotril
Shafaat et al. Novel nanoemulsion as vehicles for transdermal delivery of Clozapine: In vitro and in vivo studies
WO2015186040A1 (fr) Composition de nanoémulsion stable
US20120308663A1 (en) Lipid nanocapsules, method for preparing same and use thereof as a drug
Chen et al. Optimized mixed oils remarkably reduce the amount of surfactants in microemulsions without affecting oral bioavailability of ibuprofen by simultaneously enlarging microemulsion areas and enhancing drug solubility
WO2005014048A1 (fr) Preparations a emulsification spontanee et a micro-emulsification spontanee pour l'administration orale de taxoides
Rao et al. Formulation and evaluation of liquid loaded tablets containing docetaxel-self nano emulsifying drug delivery systems
US20080064760A1 (en) Spontaneously Dispersible Pharmaceutical Composition
WO2007006334A1 (fr) Microemulsion pharmaceutique aqueuse et transparente comprenant du propofol, et son procede de preparation
Qader et al. Novel oral solid self-nanoemulsifying drug delivery system (S-SNEDDS) of rosuvastatin calcium: Formulation, characterization, bioavailability and pharmacokinetic study
JP6618488B2 (ja) テストステロンウンデカノエートの安定な製剤
Wang et al. Microemulsions for drug solubilization and delivery
Syukri et al. Fabrication of Propolis Self-Nano Emulsfying Using Virgin Coconut Oil as Lipid-Based Vehicle
KR20140057048A (ko) 보르테조밉 함유 경구용 약학 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15802876

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15802876

Country of ref document: EP

Kind code of ref document: A1