Transcription of Lipid Nanoparticles
1 PharmaSolThe Solubility PeopleLipid Nanoparticles for the delivery of activesin pharma, cosmetics & consumer carePharmaSol GmbHNo. 1No. 1 Cornelia M. KeckPharmaSol GmbHBerlin / GermanyNLC Nanopearls PharmaSolThe Solubility PeopleContentShort look into history of liposomesDefinitions & special featuresStructure of Lipid particle matrixProduction process & large scale production linesoral bioavailibility case studiesPharmaSol GmbHNo. 2No. 2oral bioavailibility case studies- cyclosporine and testosteronundecanoate (TU)dermal applicationMake-ability of products products in the marketLipid Nanoparticles versus liposomesSummaryPharmaSolThe Solubility People1968 Invention of liposomes by Bangham( liposome size in nanometer range, liposomes were nanotechnology)Let us go back in cosmetic GmbHNo.
2 3No. 31986 Introduction of first cosmetic product to market:Capture by learn from history for future innovative productsPharmaSolThe Solubility PeoplePharmaSol GmbHNo. 4No. 4 PharmaSolThe Solubility PeopleExtraordinary market success:Most people did not know what a liposome isbutthey bought the product when the name liposome was on the PharmaSol GmbHNo. 5No. 5they bought the product when the name liposome was on the packaging!Association: liposome = qualityAssociation: liposome = qualityPharmaSolThe Solubility PeopleNanocarrier history since the liposomes many attemptsto develop a similar successful system examples:nanoemulsionsPharmaSol GmbHNo.
3 6No. 6 examples:nanoemulsionsmicroemulsionsmult iple emulsionstransfersomes(by Cevc / Munich, Germany)PharmaSolThe Solubility People2005 The novel approach in cosmetics & pharma:PharmaSol GmbHNo. 7No. 7 NLC = Nanostructured Lipid CarriersPharmaSolThe Solubility PeopleContentShort look into history of liposomesDefinitions & special featuresStructure of Lipid particle matrixProduction process & large scale production linesoral bioavailibility case studiesPharmaSol GmbHNo. 8No. 8oral bioavailibility case studies- cyclosporine and testosteronundecanoate (TU)dermal applicationMake-ability of products products in the marketLipid Nanoparticles versus liposomesSummaryPharmaSolThe Solubility PeopleDevelopment of Lipid nanoparticle conceptTraditional CarriersLipid Nanoparticles1970ies1950ies19911999/2000 PharmaSol GmbHNo.
4 9No. 9 Polymeric nanoparticlespolymer(solid)liquid Lipid (=oil)o/w emulsionsolid lipidSLN1stgenerationsolid Lipid blendNLC2ndgenerationsurfactant/ stabilizer layerPharmaSolThe Solubility PeopleLipid Nanoparticles in solid state: derived from o/w emulsions simply replacing the liquid Lipid (= oil) by a solid Lipid ( solid at body temp.)DefinitionsPharmaSol GmbHNo. 10No. 10 SLN Solid Lipid Nanoparticles produced from 1 solid lipidNLC Nanostructured Lipid Carriers: produced from blend of solid and liquid lipids but particles are in solid state at body temperature PharmaSolThe Solubility PeopleFeaturesLipid Nanoparticles with solidmatrixMean particle diameter: 80 - 1000nmProduction by dispersion techniques, high pressure homogenizationLoading* with active compounds, GmbHNo.
5 11No. 11 Loading* with active compounds, prednicarbate, prednisolone, cyclosporine Benzophenone-3, Allure6% Retinol (Vitamin A)24% Tocopherol (Vitamin E)(* calculated as %age of solid Lipid matrix)PharmaSolThe Solubility PeopleNLC Technology / Nanopearls novel particulate carrier for pharmaceutical / cosmetic / nutraceutical productsNanoparticlesbased on regulatory accepted excipients physiological / natural solidlipids (renewable resources)PharmaSol GmbHNo. 12No. 12 Applicationexamples: protectionof chemically labile active compounds & controlled release (CR) - because of solid matrix penetration enhancement of actives dermal CR ( drugs, perfumes, repellents) oral absorption enhancementPharmaSolThe Solubility PeopleNLC versus SLNWhat exactly is the improvement?
6 &PharmaSol GmbHNo. 13No. 13&What are the benefits of NLC?PharmaSolThe Solubility PeopleChemical stabilisationStability of Retinol: NLC vrs. Emulsion1 PharmaSol GmbHNo. 14No. 14 NLC: Compritol ATO 888 10% stabilized with Miranol C32 Emulsion: 10% Miglyol, Tween 801 V. Jenning (1999), thesis, Free University of BerlinPharmaSolThe Solubility Peopleformation of perfect crystalline structure during storage ( modification) drug expulsionProblems of old SLNdaysPharmaSol GmbHNo. 15No. 15drugin imperfectionsdrugbetweenFA chainsdaysmonthsPharmaSolThe Solubility PeopleNLC the more intelligent systemSLN:tendency to form perfect crystals active tristearinPharmaSol GmbHNo.
7 16No. 16mixture solid & liquidlipidsNLC:inhibit crystallization process by mixing spatially very different molecules imperfections in lattice more space for drugdrugPharmaSolThe Solubility PeopleContentShort look into history of liposomesDefinitions & special featuresStructure of Lipid particle matrixProduction process & large scale production linesoral bioavailibility case studiesPharmaSol GmbHNo. 17No. 17oral bioavailibility case studies- cyclosporine and testosteronundecanoate (TU)dermal applicationMake-ability of products products in the marketLipid Nanoparticles versus liposomesSummaryPharmaSolThe Solubility PeoplePharmaSol Production TechnologyBasic principle:high pressure homogenizationequipment can be qualified & validatedPharmaSol GmbHNo.
8 18No. 18equipment can be qualified & validatedaccepted by regulatory authoritiesin production lines used for pharmaceutical parenteralsexisting industrial production linesfor cosmetics / pharmaceutical parenteral emulsions can be usedPharmaSolThe Solubility PeopleProduction Technology - Basicsbasic mixture:1. solid lipidNLC PharmaSol GmbHNo. 19No. lipid3. emulsifier4. (co-emulsifier)5. water(according to SLN patent: solid lipids , - 30% solid)NLC solid content > 30%PharmaSolThe Solubility PeopleProduction1. Meltlipid (>40 C) & dissolve active : High pressure homogenizationPharmaSol GmbHNo.
9 20No. hotsurfactant solution= pre-emulsioncoolingsolidificationNLC3. Homogenizepre-emulsionat >40oC, 250 bar, 2 cycles= nanoemulsionPharmaSolThe Solubility PeopleLipid Nanoparticles of increasing concentrationPharmaSol GmbHNo. 21No. 21conc: from 10% to about 50%PharmaSolThe Solubility PeopleAF-MICROGRAPH of Q10-loaded NanoparticlesPharmaSol GmbHNo. 22No. 22 PharmaSolThe Solubility PeopleLAB 40 discont. - 40 g batchPharmaSol GmbHNo. 23No. 23 PharmaSolThe Solubility PeopleLAB 60 - 2-10 kg batchPharmaSol GmbHNo. 24No. 24 PharmaSolThe Solubility PeopleGaulin - 150 kg/hPharmaSol GmbHNo. 25No. 25 PharmaSolThe Solubility PeopleContentShort look into history of liposomesDefinitions & special featuresStructure of Lipid particle matrixProduction process & large scale production linesoral bioavailibility case studiesPharmaSol GmbHNo.
10 26No. 26oral bioavailibility case studies- cyclosporine and testosteronundecanoate (TU)dermal applicationMake-ability of products products in the marketLipid Nanoparticles versus liposomesSummaryPharmaSolThe Solubility PeopleOral administrationExample:cyclosporineannual sales:appr. billion US $ old Sandimmun:problem:variation in BA new Sandimmun:problem: high plasma peak PharmaSol GmbHNo. 27No. 27 new Sandimmun:problem: high plasma peak (microemulsion)(> 1000 ng/ml)target of previously developed SLN:combine advantage of old & new no plasma peak &low variation in bioavailabilityPharmaSolThe Solubility PeopleOral administration - cyclosporine studyanimal:pigs(n=3)application:via gastric catheterPharmaSol GmbHNo.
