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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.
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Scientific interest?
Economic interest?
Technologies?
Barriers?
A brief taxonomic analysis of (scientific, tecnological) topicsin the scientific/tecnological literature
• Natural phenomena of relevance• Tecnologies (patented or free)• Processes• Devices• Commodities• Newly coined terms
Analysis of microencapsulation business…
1. Cancer2. Climate Change3. Stem cell4. Laser5. Transistor6. Graphene7. Electrospray8. Scale free9. Microencapsulation10.Flow Focusing®
Selected topics:
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.
is able to produce microparticles of required composition
and homogeneous size, in a gentle way.The jet goes out through the outlet without touching the edges.
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1950 1960 1970 1980 1990 2000 2010 2020
Researchers (OCED)
All peer reviewed articles (Scopus, SCI)
Laser
Electrospray*
Microencapsulation & Solvent Extraction
Stem Cell*
Scientific publication (number of articles). Selected topics
Growth Analysis
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1950 1960 1970 1980 1990 2000 2010 2020
Share per subject in total. Selected topics
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1950 1960 1970 1980 1990 2000 2010 2020
Cancer*
Laser
Electrospray*
Microencapsulation & Solvent Extraction
Transistor
Stem Cell*
Growth Analysis
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• Electrical permittivity
• Physicochemical properties• Diffusivities (linear & non-linear, subdiffusivities)• Chemical potentials• Phase change heats (evaporation, melting, etc.)• Formation enthalpies
2- Operational parameters
• Geometry• Pressure, Flow rate• Applied electromagnetic fields
Number of governingparameters >3
(All this does not necessarilyimply lack of robustness)
• 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)
Tran, Benoit, Venier-Julienne, Int. J. Pharmaceutics 407, 1-11 (2011)
Not true
Dendukury, Doyle. (Polymeric microparticles using microfluidics) Adv. Mat. 21, 4071-4086 (2009)
Flow Focusing
Selectable Size: for each way of administration
From mm down to several hundreds nm
Easy and simple: in just one step
High Accuracy: dose control, cost effective, CV < 8%
No sieving, filtering, no cyclones, no additional steps
Versatility: No limits on formulation, any liquid
We just need a liquid or a emulsion (fluid)
Validated for many different substances and shell materials
Very smooth mechanical process:
Extra stability and bioavailability (no damage to molecules or microorganisms)
®
High Value Starting Material +Additives +Polymeric Matrix
Homogeneous solutions, suspensions, emulsions, melted substances, etc
Developed formulation
Ionic gelation, hot air, extractionevaporation …
Solidification/ Hardening
Focusing with air or water
®
®
true, direct, one-step
®
Polymeric Matrix + Additives
Homogeneous solutions, suspensions, emulsions, etc
Most common formulation
Ionic gelation, hot air, extractionevaporation …
Solidification/ Hardening
Focusing with air or water
High Value Starting Material + Additives
Homogeneous solutions, suspensions, emulsions, melted substances, etc
®
0.9 microns 5 microns 15 microns
350 microns 1500 microns
3500 microns
7000 microns
50 microns
®
37 microns
11 microns
15 microns
5 microns
®
Lactobacilus, 31 um Omega 3, ~ 80 um Flavour , 40 um
Peptide, 800 nm Anti inflammatory, 8 umVitamin A, ~ 90 um
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gelation
FORMULATION
Homogeneous solutions
Emulsions
SuspensionsAPI 12 um
Maltodextrin, 22 um
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gelation
FORMULATION
Homogeneous solutions
Emulsions
SuspensionsOily emulsion 38 um
Protein, 14 um
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gelation
FORMULATION
Homogeneous solutions
Emulsions
SuspensionsLactobacilus, 31 um
Magneticnanoparticles, 5 um
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gelation
FORMULATION
Homogeneous solutions
Emulsions
Suspensions Oily emulsion 38 um
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)
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gelation
FORMULATION
Homogeneous solutions
Emulsions
SuspensionsOmega 3, ~ 80 um
Flavor 40 um
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gelation
FORMULATION
Homogeneous solutions
Emulsions
Suspensions
Magneticnanoparticles, 5 um
Protein, 14 um
→ ® →
HARDENING
Spray Drying
Spray Chilling
Extraction/Evaporation
Ionic Gellation
FORMULATION
Homogeneous solutions
Emulsions
SuspensionsLactobacilus, 31 um
Stem cells, ~170 um
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 of
extremely fine droplets within a desired range when monodispersion 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).
Shellac, 0.5-7 um
Maltodextrin, 0.3-4 um
Increases production
Increases micrometric dispersion level
Ability to work with conflicting dispersions and high viscosity materials
High operational robustness
Low energy consumption
Simplicity
Tested with nanoclays, lixiviates,… Dye in polystyrene, 5 um, CV 69%
QUICK SPEC ON INGENIATRICS' CAPABILITIES
Flow Focusing® NozzlesSD FF100, SD FF200, SD FF 350, SD FF500,
SD FF700From several microns to
tens/hundreds of microns
Flow Focusing®
Concentric NozzlesSD cFF 350, SD cFF500
From several microns to tens of microns
Flow Blurring® Nozzles SD FB240, SDFB500From nanometers to few tens of
microns
Polymers
Gums: arabic gum, shellac, etc.Celluloses: EC, CMC, HPMCP,etc
Acrylic derivatives: Eudragits (S100, E100, NM30D), etc Polyvinyl derivatives: Sureteric, Kollidon, etc
Poly ester derivatives: PLGAOthers: Lactose, maltodextrines, alginates, mixtures of various
Products in formulation Drugs, Food ingredients, Oils (by emulsification), enzymes, particles
(suspensions), Additives (glidance, adsorbents, plasticizers, etc)
Products in inner core (for concentric)
Emulsions, fragrances, drugs, oils, pigments, etc ..
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Our technological service offer Development & Production of high value microspheres based on our proprietary technology for Microencapsulation:
Study and evaluation of starting material.
Design of innovative solutions for the required application based 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.PI Parque Plata. C/Camino Mozárabe, 4141900 Camas, Sevilla. España/Spain
T. (+34)954 081 214 F. (+34)955 980225
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