Devil's in details. Physics and chemistry behind SUCCESSFUL microencapsulation
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Devil's in details. Physics and chemistry behind SUCCESSFUL microencapsulation

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From molecules to biological systems - careful attention to specific details in the formation of droplets, microparticles and core-shell capsules is the key to successful microencapsulation.

From molecules to biological systems - careful attention to specific details in the formation of droplets, microparticles and core-shell capsules is the key to successful microencapsulation.

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Devil's in details. Physics and chemistry behind SUCCESSFUL microencapsulation Devil's in details. Physics and chemistry behind SUCCESSFUL microencapsulation Presentation Transcript

  • Scientific interest?Economic interest?Technologies?Barriers?
  • Analysis of microencapsulation business…A brief taxonomic analysis of (scientific, tecnological) topics in the scientific/tecnological literature • Natural phenomena of relevance • Tecnologies (patented or free) • Processes • Devices • Commodities • Newly coined terms
  • Selected topics:1. Cancer2. Climate Change3. Stem cell4. Laser5. Transistor6. Graphene7. Electrospray8. Scale free9. Microencapsulation10.Flow Focusing®
  • is able to produce microparticles of required compositionand homogeneous size, in a gentle way.The jet goes out through the outlet without touching the edges. 3-D focusing of the micro-jet by means of a mechanical process: pressurized air, gas or liquid. No smashing, no electricity, no chemical process needed. The same nozzle allows the direct production of selectable, homogeneous sizes within an ample range.
  • Scientific publication (number of articles). Selected topics Growth Analysis10000000 Researchers (OCED) All peer reviewed articles (Scopus, SCI) 1000000 100000 Laser Stem Cell* 10000 Electrospray* 1000 100 10 Microencapsulation & Solvent Extraction 1 1950 1960 1970 1980 1990 2000 2010 2020
  • Share per subject in total. Selected topics 1 Growth Analysis 0,1 Cancer* Laser 0,01 Stem Cell* Transistor Electrospray* 0,001 0,0001 0,00001 Microencapsulation & Solvent Extraction0,0000010,000000 1950 1960 1970 1980 1990 2000 2010 2020
  • Growth Analysis
  • Analysis of current trends
  • Analysis of current trends
  • Analysis of current trends
  • Analysis of current trends
  • … Not a bad position. However… Barriers? Intrinsic difficulties? Parametrical variety:1- Physical properties of materials• Surface tension• Density• Viscosity (Newtonian & Non-Newtonian; Rheology)• Electrochemical properties • Electrical mobilities, conductivity Number of governing • Electrical permittivity parameters >3• Physicochemical properties • Diffusivities (linear & non-linear, subdiffusivities) • Chemical potentials • Phase change heats (evaporation, melting, etc.) • Formation enthalpies2- Operational parameters• Geometry (All this does not necessarily• Pressure, Flow rate imply lack of robustness)• Applied electromagnetic fields
  • • Power of dimensional analysis and non-dimensional parameters: • M. Levin. Pharmaceutical process scale up. Marcel Dekker Inc (2002). • G. I. Barenblatt. Scaling. Cambridge U. Press (2003)• Droplet (simple, compound…), microparticle production • Basaran. AIChE J. 48, 1842-1848 (2002) • Dendukury, Doyle. Adv. Mat. 21, 4071-4086 (2009) • Anna, Bontoux, Stone. Appl. Phys. Lett. 82, 364-366 (2003) • Ganan-Calvo. Phys. Rev. Lett. 80, 285-288 (1998)• Microcapsule hardening: • By spray drying: Vehring, Pharmaceutical Particle Engineering via Spray Drying. Pharmaceutical Research 25, 999-1022 (2008) • By solvent extraction: • Freitas, Merkle, Gander. J. Control. Release 102, 313-332 (2005); • Martín-Banderas et al. Adv. Mater. 18, 559-564 (2006); • Li, Rouaud, Poncelet. Int. J. Pharma. 363, 26-39 (2008)
  • Basaran, AIChE J. 48, 1842-1848 (2002)
  • Not trueTran, Benoit, Venier-Julienne, Int. J. Pharmaceutics 407, 1-11 (2011)
  • Flow FocusingDendukury, Doyle. (Polymeric microparticles using microfluidics) Adv. Mat. 21, 4071-4086 (2009)
  • Selectable Size: for each way of administration From mm down to several hundreds nm Easy and simple: in just one stepHigh Accuracy: dose control, cost effective, CV < 8% No sieving, filtering, no cyclones, no additional stepsVersatility: No limits on formulation, any liquid We just need a liquid or a emulsion (fluid) Validated for many different substances and shell materialsVery smooth mechanical process: Extra stability and bioavailability (no damage to molecules or microorganisms)
  • ®High Value Starting Material + Homogeneous solutions, suspensions, emulsions, meltedAdditives + substances, etcPolymeric Matrix Developed formulation Focusing with air or water Solidification / Hardening Ionic gelation, hot air, extraction evaporation …
  • ® ®true, direct, one-step
  • ® Most common formulation Homogeneous solutions, suspensions, emulsions, etc Polymeric Matrix + Additives Focusing with air or waterHigh Value Starting Material Solidification+ Additives / HardeningHomogeneous Ionic gelation, hot air, extractionsolutions, suspensions, emulsion evaporation …s, melted substances, etc
  • ®0.9 microns 5 microns 15 microns 50 microns350 microns 1500 3500 7000 microns microns microns
  • ®11 microns 5 microns37 microns 15 microns
  • ®Lactobacilus, 31 um Omega 3, ~ 80 um Flavour , 40 umVitamin A, ~ 90 um Peptide, 800 nm Anti inflammatory, 8 um
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions API 12 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Ionic Gelation Maltodextrin, 22 um
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions Oily emulsion 38 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Ionic Gelation Protein, 14 um
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions Lactobacilus, 31 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Ionic Gelation Magnetic nanoparticles, 5 um
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions Oily emulsion 38 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Ionic Gelation Flavor 37 um
  • Spray drying: morphological effects.Influence of the rate of evaporation over the rate of diffusion (Peclet number)Vehring, Pharmaceutical Particle Engineering via Spray Drying. Pharmaceutical Research 25, 999-1022 (2008)
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions Omega 3, ~ 80 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Ionic Gelation Flavor 40 um
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions Protein, 14 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Ionic Gelation Magnetic nanoparticles, 5 um
  • → ® →FORMULATION Homogeneous solutions Emulsions Suspensions Lactobacilus, 31 umHARDENING Spray Drying Spray Chilling Extraction/Evaporation Stem cells, ~170 um Ionic Gellation
  • 3 pilot-plants, 2 assembly rooms: Pharmaceutical – (ISO Class 7)–Certified ISO 9001:2008, ISO 14001:2004, GMP in progress Food - (ISO Class 8) –Certified ISO 9001:2008, ISO 14001:2004 Chemistry – Certified ISO 9001:2008, ISO 14001:2004
  • cutting-edge technology to produce a spray ofextremely fine droplets within a desired range whenmonodispersion is not strictly required. Uses efficient micro-mixing of fluids using a reflux cell. Technology: pneumatic atomization with the highest efficiency (up to many thousands more energy- saving).
  • Increases production Increases micrometric dispersion level Ability to work with conflicting dispersions Shellac, 0.5-7 umand high viscosity materials High operational robustness Low energy consumption Simplicity Maltodextrin, 0.3-4 um Tested with nanoclays, lixiviates,… Dye in polystyrene, 5 um, CV 69%
  • QUICK SPEC ON INGENIATRICS CAPABILITIES SD FF100, SD FF200, SD FF 350, SD FF500, From several microns toFlow Focusing® Nozzles SD FF700 tens/hundreds of microns Flow Focusing® From several microns to tens of SD cFF 350, SD cFF500 Concentric Nozzles microns From nanometers to few tens ofFlow Blurring® Nozzles SD FB240, SDFB500 microns Gums: arabic gum, shellac, etc. Celluloses: EC, CMC, HPMCP,etc Acrylic derivatives: Eudragits (S100, E100, NM30D), etc Polymers Polyvinyl derivatives: Sureteric, Kollidon, etc Poly ester derivatives: PLGA Others: Lactose, maltodextrines, alginates, mixtures of various Drugs, Food ingredients, Oils (by emulsification), enzymes, particlesProducts in formulation (suspensions), Additives (glidance, adsorbents, plasticizers, etc)Products in inner core Emulsions, fragrances, drugs, oils, pigments, etc .. (for concentric)
  • 37
  • Our technological service offer Development &Production of high value microspheres based on ourproprietary technology for Microencapsulation: Study and evaluation of starting material. Design of innovative solutions for the required applicationbased on our technology. Pre-formulation studies and technology fitting. Microparticle characterization : morphology, composition, analytical methods, etc. Initial studies: stability, drug delivery profiles… Scale-up and microparticle production.Plata. C/Camino Mozárabe, 41 PI Parque 41900 Camas, Sevilla. España/Spain T. (+34)954 081 214 F. (+34)955 980225