HSP, a mighty tool for formulation applications Application note

Executive summary

Field of applicationsFormulation | Pharmaceutical industry | Cosmetics | Inks | Food Industry | Lubricant

Many practical chemical products are actually formulations, i.e. sophisticated mixtures of numerous compounds that can be liquids or solids.

How to select them e!ciently without costly and time-consuming tests?

Hansen Solubility Parameters (HSP) are one of the most used prediction tools to perform such selections. The HSP define the material properties in three dimensions, the disperse, the polar and the hydrogen-bonding properties ( , and ), which are used by formulators to predict the compatibility of com-pounds in mixture. However, the HSP of most compounds are not known and can be di!cult to determine, especially for liquids. Indeed, their values are often not measured experimentally but rather computed on theoretical basis.

In this application note, we show how Inverse Gas Chromatography (IGC) is able to measure the HSP of liquid substances by testing their interaction ability toward 20 di"erent solvents. Our method makes it possible to perform the HSP measurement within a day (including reproducibility tests for each solvents) and using reduced material and solvents amounts. Moreover, the generated IGC data can be imported and directly processed by the HSPiP software used by groups around the world to optimize formulations via HSP techniques. This method can easily be applied to oils, surfactants, polymers above Tg and any liquid additives. As an example, two liquids were analyzed: Olive Oil and PEG400.

Principle

Examples

Objectives

Th

e pu

rpo

se here is to

dem

on

strate the ab

ility of th

e Inverse G

as Ch

rom

atog

raph

y (IGC

) to d

etermin

e the

Han

sen So

lub

ility Param

eters (HSP

). HSP

analysis is a p

ow

erful an

d p

ractical way to

better u

nd

erstand

issues

of so

lub

ility, disp

ersion

, di"

usio

n, ch

rom

atog

raph

y and

mo

re [1]. In th

is app

lication

no

te, two

liqu

id-b

ased

materials, o

live oil an

d P

EG4

00

, are used

as an exam

ple to

express th

e po

tent ad

vantag

es of su

ch tech

niq

ue

for th

e determ

inatio

n o

f HSP.

Th

e Han

sen So

lub

ility Param

eters (HSP

) were in

i-tially d

evelop

ed b

y Ch

arles M. H

ansen

in 19

67 as

a too

l for p

redictin

g if o

ne m

aterial will d

issolve in

an

oth

er and

form

a solu

tion

. Tod

ay, they are w

idely

used

to p

redict ch

emical co

mp

on

ent co

mp

atibili-

ties in m

ixture an

d to

accelerate the d

evelop

men

t o

f form

ulatio

ns o

f inks, p

aints, ad

hesives, co

smetics

or p

harm

aceuticals. H

SP d

ivide th

e total so

lub

ility p

arameter (

) into

three in

divid

ual p

arts arising

fro

m d

ispersio

n fo

rces betw

een m

olecu

les (),

energ

y from

dip

olar in

termo

lecular fo

rces betw

een

mo

lecules (

), and

hyd

rog

en-b

on

din

g (

). T

he H

SP d

etermin

ation

s can b

e achieved

by in

verse g

as chro

mato

grap

hy at in

finite d

ilutio

n co

nd

ition

s (IG

C-ID

) [2, 3, 4] co

mb

ined

with

the H

SPiP

softw

are d

evelop

ed b

y Pr. Steven

Ab

bo

tt, Dr C

harles H

ansen

an

d D

r Hiro

shi Yam

amo

to [5, 6

]. Ad

scientis d

eve-lo

ped

, the N

euro

nic so

lutio

n, a m

etho

d to

measu

re th

e HSP

of liq

uid

sub

stances. In

oth

er wo

rds, 20

m

olecu

lar pro

bes (so

lvents) are in

jected at very

low

con

centratio

n in

a stainless-steel co

lum

n filled

w

ith th

e sub

stances to

be in

vestigated

coated

on

to

a suitab

le packin

g m

aterial. Th

eir retentio

n tim

e is m

easured

. Th

e surface o

f the su

pp

ort n

eeds to

b

e fully co

vered (15%

-20%

in w

eigh

t). Hen

ce, it is

Th

e net reten

tion

time (

) of each

pro

be

(, w

ith

the reten

tion

time o

f the

peak o

f the p

rob

e and

th

e retentio

n tim

e of a

no

n-retain

ed p

rob

e like meth

ane).

Th

e specific reten

tion

volu

me (

) derived

from

th

e b

y the fo

llow

ing

equ

ation

:

(1)

With

th

e measu

remen

t temp

erature in

,

th

e corrected

carrier gas flo

w an

d

the w

eigh

t o

f dep

osited

samp

le.

Ch

emical co

mp

on

ent co

mp

atibilities are cru

cial param

eters need

ed b

y inks-, p

aints- ad

hesives-, co

sme-

tics- and

ph

armaceu

ticals- ind

ustries an

d acad

emic lab

s. Two

liqu

id m

aterials are con

sidered

: olive o

il and

P

EG4

00

. To p

rovid

e go

od

, accurate an

d rep

rod

ucib

le data, A

dscien

tis has d

efined

a tho

rou

gh

pro

cedu

re for

the d

etermin

ation

of th

e HSP. Fo

r that, th

e liqu

id m

aterial was d

epo

sited o

n th

e chro

mato

grap

hic statio

nary

ph

ase in a th

ick layer by an

imp

regn

ation

meth

od

. For th

at step, it is im

po

rtant to

ob

tain a h

om

og

eneo

us

coverin

g an

d th

ick eno

ug

h layer o

f the ch

rom

atog

raph

ic sup

po

rt by th

e liqu

id m

aterial. Th

e HSP

values can

b

e determ

ined

at amb

ient o

r hig

her tem

peratu

re dep

end

ing

on

the p

hysical state o

f the su

bstan

ces to b

e in

vestigate (liq

uid

, pasty o

r solid

).

Th

e HSP

measu

remen

ts by IG

C-ID

on

olive o

il an

d P

EG4

00

are achieved

at 25 °C. T

he sam

e set o

f twen

ty pro

be m

olecu

les is injected

on

bo

th

samp

les. Each m

olecu

le is ind

ividu

ally injected

several tim

es to m

easure a m

ean valu

e and

a stan-

dard

deviatio

n o

f their reten

tion

time (

). Eq

uatio

n (1) w

as then

used

to co

mp

ute th

e cor-

respo

nd

ing

specific reten

tion

volu

me (

) of each

p

rob

e. Th

ese values w

ere directly u

sed to

com

pu

te th

e HSP

values w

ith th

e HSP

iP so

ftware.

Th

e softw

are first com

pu

tates the exp

erimen

tal Flo

ry-Hu

gg

ins in

teraction

param

eter () [1, 3, 6

]. T

he H

SP co

mp

on

ents o

f the sam

ple, (

), () an

d

() are th

en calcu

lated u

sing

an iterative m

etho

d.

Th

is iterative meth

od

aims at m

aximizin

g th

e co

rrelation

coe!

cient (

) fit value b

etween

expe-

rimen

tal an

d calcu

lated

values b

ased o

n th

e “d

istance” b

etween

the H

SP valu

es of th

e pro

bes

and

the cu

rrent estim

ate HSP

values o

f the sam

ple.

Th

e algo

rithm

uses all th

e available p

rob

es to co

m-

pu

te the

, an

d

values th

at are best fittin

g th

e exp

erimen

tal valu

e.

Th

e final reg

ression

grap

hs fo

r the co

mp

utatio

n

of th

e three co

mp

on

ents o

f PEG

40

0 an

d o

live oil

are also d

on

e on

the co

mp

lete set of so

lvents u

sed

as pro

bes. T

he co

mp

utatio

n o

f the th

ree HSP

of

PEG

40

0 an

d O

live Oil are resp

ectively sho

wn

on

Fig

ure 3 (to

p) an

d Fig

ure 3 (b

otto

m). T

he b

est fitting

H

ansen

Solu

bility p

arameters o

f PEG

40

0 an

d o

live o

il com

pu

ted w

ith th

e HSP

iP so

ftware are g

athered

in

Table 1.

Samp

le

PEG

40

021.1

10.2

8.4

0.9

44

Olive o

il17.0

0.3

4.10

.96

1

Parameters and softw

are to be used for the HSP determ

inations:

General scope:

Results:

assum

ed th

at the su

pp

ort d

oes n

ot co

ntrib

ute to

th

e pro

be’s reten

tion

time. T

his m

etho

d m

akes it p

ossib

le to p

erform

the H

SP m

easurem

ent w

ithin

a d

ay (inclu

din

g rep

rod

ucib

ility tests for each

sol-

vents) an

d u

sing

on

ly small am

ou

nts o

f material an

d

solven

ts. With

this m

etho

d, w

e measu

re a mean

valu

e and

a stand

ard d

eviation

of th

eir retentio

n

time (

). Th

e specific reten

tion

volu

me (

) is then

d

erived fro

m th

e retentio

n tim

e () an

d can

be

directly im

po

rted in

to th

e HSP

iP so

ftware.

Th

e HSP

iP so

ftware p

rovid

es the alg

orith

m an

d

com

pu

tation

meth

od

for th

e HSP

determ

ina-

tion

s. Probe

InjectionAdsorption/Desorption

Detection

Studied substancesEluted peak

Retention time

Studied liquid sample

coated on supportSupport

Experimental

-2-1

01

23

4-2 -1 0 2 41 3

Calculated

-2-1

01

23

4-2 -1 0 2 41 3

IGC: PEG

400

IGC: O

live Oil

Experimental

Calculated

Signal ( )

Time (m

in)

Hexane probeHeptane probe

Octane probe

0

0.2

0.4

0.8

1.0

050

100150

200250

300

HexaneHeptane

Octane 3 measurements

0 1 2 3 54

(cm3)

0.56 0.01+

1.58 0.04+

4.35 0.11+

Figure 1 Principle of IGC-ID

Figure 3 Example of HSP com

putation forPEG400 (top) and Olive Oil (bottom

)

Table 1 HSP measured at 25°C for both sam

ples(given in M

Pa1/2)

Figure 2 Reproducibility of measurem

ents on 3different probes (Std. dev. < 2.5%

)»

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ConclusionsThis short note demonstrates the ability of Inverse Gas Chromatography to determine accurately the Hansen Solubility Parameters of two liquid mate-rials: olive oil and PEG400. This method has great flexibility as it can obviously be extended to any kind of non-volatile liquid materials. Hence, IGC is a direct and rapid technique, needing really small quantities of products, to determine the HSP with good reproducibility and accuracy.

Furthermore, its combination with the HSPiP com-putation software makes it a powerful tool to obtain information on the compatibility of a liquid material with another. Finally, within a day, the specific re-tention time of 20 molecular probes can be deter-mined by IGC and computed in the software for the calculation of the HSP. We expect this method to hasten and improve significantly the ability to for-mulate intelligently new materials formulation.

Customers

Contact

Dr. Ralf DUMPELMANNTel: +41 62 873 13 11ralp.dumpelmann@inolytix.com

Dr. Jo!rey HUVEBusiness ManagerTel: +33 3 89 48 00 42j.huve@adscientis.com

For Germany, Austria and Switzerland:

ref 1. C. Hansen, Hansen Solubility Parameters: A user’s handbook, Second Edition. 2007, Boca Raton, Fla: CRC Press

ref 2. IGC-ID sheet, Adscientis

ref 3. S. Abbott, IGC Science: Principles and Practice, 2018

ref 4. https://www.adscientis.com

ref 5. https://www.stevenabbott.co.uk/practical-chromatography/hsp.php

ref 6. https://www.hansen-solubility.com/HSPiP/

References