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.

1

10

100

1000

10000

100000

1000000

10000000

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

0,000000

0,000001

0,00001

0,0001

0,001

0,01

0,1

1

1950 1960 1970 1980 1990 2000 2010 2020

Share per subject in total. Selected topics

0,000000

0,000001

0,00001

0,0001

0,001

0,01

0,1

1

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 ..

37

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