Controlled delivery of water-insoluble active ingredients in air from hydrogel matrices

C. Dispenza1,2, G. Giammona3, M. Licciardi3, C. Lo Presti1, M. Ricca1, C. Spadaro1

1Dept. of Processing and Materials Chemical Engineering (DICPM)

2Interdept. Research Centre on Composite Materials (CIRMAC)

Dipartimento di Chimica e Tecnologie Farmaceutiche

SIBPA, Palermo 17-22 September 2006

logoUniversità di Palermo

Contents:

The context

“Functional” hydrogels from colloidal systems

“Functional” hydrogels obtained through ionising irradiation

Release behaviour of a model fragrance

Conclusions

Sensory properties in consumer products

CONSUMER PRODUCT

Informed choices

Value-based choices

Impulse-based choices

CONSUMER BEHAVIOUR

performance

appearance

experience

• Foods• Cosmetics• Smoke• Housefield• Paints and coatings

• Paper• Textiles• Automotive • ICT• …

Major investor for research & development in the field of smart delivery of fragrances: Nissan!

• Essential oils• Aroma chemicals• Absolutes• Balsams• Concentrated oils• Essences• Extracts• Resins• Infusions

Polymers delivering olfactory sensations

• Aromatic esters

• Aliphatic esters

• Ethers

• Ketones

• Alcohols

Micelles Vesicles

ACTIVE INGREDIENTS

d= 100 - 600 m

INCORPORATED / ENCAPSULATED INTO A POLYMER

dry powders

creams, foams, lotions, ect.

DISPERSED/EMULSIFIED

BARRIER MATERIALS

DIFFERENT ARCHITECTURES FORMED BY BLOCK-COPOLYMERS IN WATER

Bicontinuous phases Hexagonally packed vescicles Lamellae

• INERT, BIOCOMPATIBLE, BIODEGRADABLE

• HIGH LOADING CAPACITIES(non equilibrium systems & processes)

• Ensuring SYNCHRONISATION between the required TIME FOR THE SENSORIAL EFFECT and the actual RELEASE PROFILE

• Ensuring SITE OF RELEASE RECOGNITION

• Relatively STABLE TO STORAGE conditions over a long period of time

(for cosmetics: 2-3 years)

Polymers as delivery devices, some requirements…

Hydrogels by definition

High water content (>20% - 1000%)3D network structure with soft consistencyElastic structure with a memorised reference configuration

Linear polymer strands

PHYSICAL GEL

CHEMICAL GELS

“Virtual” cross-links formed by chain entanglements, electrostatic forces, hydrogen bonds

T, pH, solvents+ chem. reaction

+ chemical cross-links

DISSOLUTION SWELLING

+ H2O

T, pH, solvents

Tridimensional polymeric networks:

Ionising irradiation

Water + cross-linked polymer =

Water + water-soluble monomers and/or polymers

“Functional” hydrogels through ionising irradiation

CROSSLINKING of hydrophilic MONOMERS and POLYMERS (+ X-linking agents + initiators/catalysts) by thermal activation

• Complementary reactive groups: hydroxyl-aldehydes, amine-carboxylic acid, isocyanate-OH / NH2 etc.

• Reactive double bonds

crosslinksP

POHHPOH

eOHHOH aq

2

2 ,,Ionising

irradiation

IONIZING IRRADIATIONIONIZING IRRADIATION

The other way…

…to create reactive sites andpromote reactivity!

= IN SITU “FUNCTIONAL” HYDROGEL

“Functional” hydrogels through ionising irradiation

H y d r o p h i l i c m o n o m e r s a n d / o r p o l y m e r s

D i s p e r s e d “ o b j e c t s ” f r o m 5 u p t o 5 0 0 n m o f a v e r a g e d i a m e t e r

I R R A D I A T I O NW a t e r+ W a t e r

C r o s s l i n k e d p o l y m e r

“Active” ingredient:

• Water-insoluble molecules•heat sensitive and/or volatile

• Water-insoluble polymers(1,2)

•conductive polymers obtained via dispersion polymerisation

Water- insolubleActive Ingredient

Polymeric surfactant

Ionising irradiation

1 C. Dispenza, C. Lo Presti, C. Belfiore, G. Spadaro, S. Piazza, Polymer, 47, 961-971, 2006.

2 C. Dispenza, M. Leone, C. Lo Presti, F. Li Brizzi, G. Spadaro, V. Vetri, Journal of Non-Crystalline Solids, 352 (2006) 3835–3840.

DISPERSED “OBJECT”

flavours (aromas) and fragrances

H y d r o p h i l i c m o n o m e r s a n d / o r p o l y m e r s

D i s p e r s e d “ o b j e c t s ” f r o m 5 u p t o 5 0 0 n m o f a v e r a g e d i a m e t e r

I R R A D I A T I O NW a t e r+ W a t e r

C r o s s l i n k e d p o l y m e r

‘In-house’ developed, flexible polymer chemistry from..

HC

C

NH

NH

HC C

CH2

O

NH CH2 CH2 OH

C O

NH

O

C

O

NH CH2 CH2 OH

CH2

-POLY(N-2-HYDROXYETHYL)-D,L-ASPARTAMIDE

PHEA

Grafting of double bonds for easy of crosslinking

Grafting functional groups for stimuli sensitivity

Co60 gamma irradiator

( IGS-3 at Palermo University)

60 Co

1.33 MeV

60Co = 60 Ni + e -+ ’1.17 MeV

DOSE : 2,5-3,5 kGyDOSE RATE: 0,5 kGy/h

Gray: 1J of energy absorbed by 1 Kg of matter

Experimentals

PHEA + GMA = PHG

PHG + water + rays= PHG hydrogel

(Derivatisation degree= 0,3)

5% wt/vol PHG/water

H y d r o p h i l i c m o n o m e r s a n d / o r p o l y m e r s

D i s p e r s e d “ o b j e c t s ” f r o m 5 u p t o 5 0 0 n m o f a v e r a g e d i a m e t e r

I R R A D I A T I O NW a t e r+ W a t e r

C r o s s l i n k e d p o l y m e r

‘In-house’ developed, flexible polymer chemistry from..

HC

C

NH

NH

HC C

CH2

O

NH CH2 CH2 OH

C O

NH

O

C

O

NH CH2 CH2 OH

CH2

-POLY(N-2-HYDROXYETHYL)-D,L-ASPARTAMIDE

PHEA

Grafting of double bonds for easy of crosslinking

Grafting functional groups for stimuli sensitivity

Co60 gamma irradiator

( IGS-3 at Palermo University)

60 Co

1.33 MeV

60Co = 60 Ni + e -+ ’1.17 MeV

DOSE : 2,5-3,5 kGyDOSE RATE: 0,5 kGy/h

Gray: 1J of energy absorbed by 1 Kg of matter

Experimentals

PHEA + GMA = PHG

PHG + water + rays= PHG hydrogel

(Derivatisation degree= 0,3)

5% wt/vol PHG/water

Transparent – “reversible”

Model active

Tetra- HydroGeraniol (THG): 3-7 dimethyl octanol

Polymeric surfactantBRIJ 58P: polyoxyethylene (20) cetyl ether

Experimentals

Emulsions & microemulsions

20 % vol THG/water; 2 % wt/vol BriJ/water1% vol THG/water; 3 % wt/vol BriJ/water

20 %vol THG/water; 2 %wt/vol BriJ/water + 5 %wt/vol PHG1 %vol THG/water; 3 %wt/vol BriJ/water + 5 %wt/vol PHG

Hydrogels

5 %wt/vol PHG at 2.5 kGy5 %wt/vol PHG at 3.5 kGy

3 %wt/vol BriJ/water + 5 %wt/vol PHG

20 % vol THG/water; 2 % wt/vol BriJ/water + 5 %wt/vol PHG (stirred)1 %vol THG/water; 3 % wt/vol BriJ/water + 5 %wt/vol PHG

Effect of irradiation on chemical structure

Stability prior and upon irradiation

Effect of irradiation on chemical structure

Insoluble fractionsSwelling ratios

Fragrance release behaviour

CHARACTERISATIONSMATERIAL SYSTEMS

Flux meter

in out

“STATIC” HEAD-SPACE

“DYNAMIC” HEAD-SPACE

GC analysis

GC analysis

Air supply

Experimentals

FRAGRANCE RELEASE BEHAVIOUR37°C

37°C

Cum

ula

tive T

HG

rele

ase

d,

ppm

“Static” head-space release behaviour

Time, [hr]

0

200

400

600

800

1000

0 10 20 30 40 50 60

0 kGy

2,5 kGy

3,5 kGy

Head space saturation

EMULSIONS

19753,5BriJ58P-PHG-water

27652,5BriJ58P-PHG-water

9913,5PHG-water

10862,5PHG-water

Swelling ratio [Ws/Wd]

Insoluble fraction, [%]

Dose [kGy]System

Cum

ula

tive T

HG

rele

ase

d,

ppm

“Static” head-space release behaviour

Time, [hr]

0

200

400

600

800

1000

0 10 20 30 40 50 60

0 kGy

2.5 kGy

3,5 kGy

Head space saturation

EMULSIONS

Cum

ula

tive T

HG

rele

ase

d,

ppm

0

100

200

300

400

500

600

700

800

900

0 10 20 30 40 50 60 70

Time, [hr]

0 kGy

2,5 kGy

3,5 kGy

Head space saturation

MICRO-EMULSIONS

“Dynamic” head-space release behaviour

Time, [hr]

Cum

ula

tive T

HG

rele

ase

d,

[mg]

0

1

2

3

4

5

6

7

8

9

0 10 20 30 40 50

0 kGy

3,5 kGy

2,5 kGy

Total amount of THG loaded

MICRO-EMULSIONS

0.00

0.20

0.40

0.60

0.80

1.00

1.20

0 10 20 30 40 50

Time, [hr]

Weig

ht

loss

, [

g]

0 kGy

3,5 kGy

2,5 kGy

Initial weight of water + THG

Cu

mu

lati

ve T

HG

rele

ased

, [m

g]

4,7

4,9

5,1

5,3

5,5

5,7

5,9

30 35 40 45 50 55

Time, [hr]

Re-hydration of the surface

OFFON ON OFF

2,5 kGy

SURFACE-REGULATED RELEASE MECHANISMSURFACE-REGULATED RELEASE MECHANISM

hydration

“ON-PHASE” OF THE RELEASE“OFF-PHASE” OF THE RELEASE

de-hydration

SKIN

“REVERSIBLE”!

• the faster the hydrogel looses water the sooner the skin is formed!

• the looser is the polymeric network the faster is the release of water

• water represent, by large, the main volatile component released

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 10 20 30 40 50

Time, [hr]

W(t)

W0

0 kGy

3,5 kGy

2,5 kGy

Dotted line: water + THGSolid line: THG

SURFACE-REGULATED RELEASE MECHANISMSURFACE-REGULATED RELEASE MECHANISM

Conclusions:

Ionising irradiation can be a stimulating tool to obtain “functional” hydrogels from water-soluble polymeric precursors.

Crosslinking degree and density can be controlled by tuning irradiation conditions, thus affecting the water retention properties of the gels.

Oil insoluble fragrances can be incorporated by coupling irradiation and emulsification techniques.

Hydrogel formation can prevent macroscopic phase-separation of otherwise unstable systems.

The hydrogel network offers a diffusion barrier to the fragrance.

Water loss kinetics may be exploited for a on-off, surface hydration regulated, release behavior.

Controlled delivery of water-insoluble active ingredients in air from hydrogel matrices

SIBPA, Palermo 17-22 September 2006

CONTACT DETAILSClelia DispenzaDipartimento di Ingegneria Chimica dei Processi e dei MaterialiUniversità degli Studi di PalermoTel +39 091 6567210Fax+ 39 091 6567280dispenza@dicpm.unipa.it

THANK YOU