Croda Pharma

Super Refined™
solutions for transdermal
drug delivery systems
October 2022

Smart science to improve lives™

Agenda• Introduction to Croda Pharma• Croda technology• Case studies

Smart science to improve lives™

Our journey to Croda Pharma
2022
1925

2000 onwards

2020

Croda wasfoundedOngoing investments inhigh purity excipients

Acquisition of world
leading lipid portfolio

Decades of Smart science toimprove lives™ across consumer
and health ingredients

Smart science to improve lives™

Our Health Carebusiness becomes

2018

2021

Biosector acquisition,industry leading vaccine
adjuvants

Global investments in pharma+£100m – a commitment toadvancing expertiseCroda Pharma platforms

Small Molecule
DeliveryProtein
Delivery

Nucleic Acid
Delivery

Human and Veterinary Health

Smart science to improve lives™

Adjuvant
Systems

Consumer Health
Softgels

We combine our technical expertise withregulatory knowledge to help our customers
market innovative products with consumer relevantclaims, alongside supporting formulation
development challenges within the Consumer
Health market.

Patches

Excipient solutions for:
Eye
Care

OTC
(Over-the-Counter)

Nutraceuticalsupplements
CBD

Smart science to improve lives™

Our expertiseInnovation
Enabling breakthrough innovation

Formulation
Unique blend expertise

Application
Focused scientific endeavors

Smart
Smartsciencesciencetotoimprove
improvelives™
lives™

Advantages and disadvantage oftransdermal delivery sytems (TDS)

Smart science to improve lives™

Transdermal patch design
Purpose: Deliver specific dose of medication through the skin into
the systemic circulation for therapeutic effects.
Generations of transdermal drug delivery system:
1st: Delivery candidates must be low-molecular weight, lipophilic,and efficacious at low-doses
2nd: Employed conventional chemical enhancers andelectrically assisted methods like iontophoresis
3rd: Usage of novel chemical enhancers,
electroporation, microneedles, thermal ablation or
microdermabrasion

Transdermal & Topical Delivery Systems- Product development & quality considerations, Guidance forIndustry, USFDA, November 2019 https://www.science-community.org/en/node/175244 Prausnitz MR and
Langer R. Nat Biotechnol 2008; 26(11): 1261-8.

Smart science to improve lives™

Transdermal excipients selection criteria
PolymermatrixBiologicall
y active
substance

Other
excipients

Transdermal
patch

Releaseliner

Backinglaminate

Permeationenhancers

Adhesive•

Selection of patch design•

Solubility between API and excipient blend•

Physical and chemical compatibility between API and
excipient blend•

Impact of excipient blend on skin permeation•

Impact of excipient blend on non-drug substance
related impurities•

Impact of excipients on adherence for duration of wear
periodSree Raju N et al. Chapter 2 - Transdermal and bioactive nanocarriers, Editor(s): Arun Nanda, Sanju Nanda, Tuan Anh Nguyen, Susai Rajendran, Yassine Slimani,
In Micro and Nano Technologies, Nanocosmetics, Elsevier, 2020, Pages 17-33.

Smart science to improve lives™

Transdermal API - patches
API

MW

Log P

MP (°C)

Tulobuterol

227.7

3.08

89-91

Nitroglycerin

227.1

1.62

13.5

Nicotine

162.2

1.20

90

Estradiol

272.4

4.01

173-179

Isosorbide dinitrate

236.1

1.31

70

Fentanyl

336.5

4.05

83-84

Clonidine

230.1

2.28

130

Testosterone

288.4

3.32

155

Oxybutynin hydrochloride

394.0

4.68

129-130

Scopolamine

303.4

-1.20

59

Wester RE, et. Al. Percutaneous absorption.Mecchanisms=Methodology=Drug-delivery, New York. 107-23 (1983)
Bos JD, et. At. Exp. Dermatol., 9, 165-9 (2000)
Flyn GL., et. Al., J. Pharm Sci , 39, 1043-50 (1986)
Yano T, et. Al., J. Pharm.Sci., 61, 838-52(1972)
Scheuplein RJ, et.al.,J.Invest. Dermatol, 52,63-70, (1969)
Michaels AS, et.al.,AlChe J.,21,985-96, (1969)
T.Watanabe,Drug delivery system,22,450-7,(2007)

Smart science to improve lives™

•

Low molecular weight; NMT 500 Daltons•

Moderate oil solubility log P = 1-4•

Low melting point; NMT 200°C•

Potent having dose <20mg/day•

Non-irritating and non-sensitising•

Low oral bioavailability

Croda technology
Our Super Refined™ range ensures that your formulations
are stable, effective and consistent.
• Variety of products which offer:✓ Excellent API solubility✓ Excellent oxidation stability✓ Excellent hydrolysis stability✓ Low cellular irritation✓ Better skin permeation enhancement✓ Reduced odour impact• Multicompendial - meets standards of international
pharmacopoeias; USP/NF, Ph. Eur., JP/JPE, and ChP• Excipients with a DMF submitted to the Chinese Health
Authorities (CDE)• Global manufacturing infrastructure, expert regulatory
support and application know-how

Smart science to improve lives™

Our values•

Wide range of excipient chemistries•

Solubility data - experimental•••

Solubility data - theoretical•Use of Hansen solubility parameters (HSP)
spheres for theoretical solubility prediction•

Experimental data to support excipient HSP
parameters (not just SMILES)•

Linking HSP theoretical to Smax
experimental data

Excipient stability•

Smart science to improve lives™

Testing across a wide range of API and
excipient chemistries

Batch to batch and overtime consistency

Transdermal delivery system - Croda portfolio
Product

Chemical description

Category

Monograph complianceDosage route

Max potency*****

Function

TF-ER
TS

9.6 MG
22 MG

Permeation enhancer,
solubiliser

Super Refined™ Oleic Acid

Oleic acid

Fatty acid

Ph. Eur., NF, JPE, *DMF

Super Refined DEGEE

Diethylene glycol monoethyl ether

Ether

USP/NF, Ph Eur.

TG
TS

5%
430 MG

Permeation enhancer,
solubiliser

Super Refined DMI

Dimethyl Isosorbide

Carbohydrate, sugars andderivatives

*DMF

TS

None listed

Permeation enhancer,
solubiliser

Super Refined Propylene Glycol

Propylene glycol NF

Glycols

NF, JP, *DMF

TF-ER
TG

58.13 MG
20%

Permeation enhancer,
plasticiser***, solubiliser

Super Refined Oleyl Alcohol

Oleyl alcohol

Fatty alcohol

NF

TF
TF-ER
TG
TS

6.11 MG
7.45 MG
1.5%
6.12 MG

Permeation enhancer,
solubiliser

Super Refined Oleyl Oleate

Oleyl oleate

Emollient ester

JPE

TS

30 MG

Permeation enhancer,
solubiliser

Super Refined Polysorbate 80**

Polysorbate 80

Ethoxylated sorbitan esters

Ph. Eur., NF, JP, *DMF

TS

None listed

Permeation enhancer,
surfactant

Super Refined PEG 400

Polyethylene glycol 400

Glycols

Ph. Eur., NF, JP,+DMF (grade LTG)

TS

None listed

Plasticiser****, solubiliser

Super Refined IPP

Isopropyl Palmitate

Emollient esters

NF, JPE; *DMF

TF-ER

187.5 MG

Permeation enhancer,
solubiliser

Super Refined PGML

Propylene Glycol Monolaurate

Glycol esters

NF, Ph. Eur.

TS

None listed

Solubiliser

Cithrol™ GMO HP

Glyceryl Oleate

Glyceryl esters

NF, Ph. Eur.

TF-ER

18.8 MG

Permeation enhancer*DMF submitted to the Chinese Authorities (CDE)+ DMF in process of being submitted to the Chinese Authorities (CDE)**Ref: i) Naveed et al. Trop. J. Pharm. Res., 10(3), 281-288, (2011); ii) Taghizadeh SM et al. J. Adv. Res, 6(2), 155-162, (2015).
***Ref: Panda et al. Int. J of Biological macromolecules, 6, 295-302, (2014)****Gupta et al. Int. J. Pharm, Sci. Drug Res, 1(1), 46-50, (2009)***** As listed on FDA IID inactive ingredients list
TG- Transdermal, Gel; TS- Transdermal, System; TF-ER- Transdermal Film, Extended release

Smart science to improve lives™

ChP,

Transdermal delivery system - Croda portfolio
Product

INCI Name

Category

Monograph complianceDosageroute

Max potency

Function

Crodamol™ DA Pharma

Diisopropyl adipate

Emollient esters

JPE, *DMF

TG

1.5%

Plasticiser, solubiliser

Super Refined™ Castor Oil

Castor oil

Vegetable oils

NF, JP, *DMF

TS

None listed

Plasticiser, solubiliser

Super Refined Sesame Oil

Sesame oil

Vegetable oils

NF, Ph. Eur., JP, *DMF

TS

None listed

Permeation enhancer*,solubiliser

Super Refined Olive Oil

Olive oil

Vegetable oils

JP

TS

None listed

Permeation enhancer*,solubiliser

Super Refined Ethyl Oleate

Ethyl oleate

Emollient esters

Ph. Eur.

TF-ER

15 MG

Permeation enhancer,
solubiliser

Super Refined GTCC

Medium-chain triglycerides

Emollient esters

JPE, Ph. Eur., NF, ChP,
*DMF

TS

None listed

Solubiliser

TS
TF
TF-ER
TG-M

7.25 MG58.08 MG
20.4 MG
1%

Permeation enhancer,
solubiliser

Super Refined IPM

Isopropyl myristate

Fatty acid ester

JPE, NF, Ph. Eur, *DMF

Super Refined Isostearic Acid

Isostearic acid

Fatty acids

JPE

TS

None listed

Permeation enhancer**,plasticiser, solubiliser

Super Refined Hexyl Laurate

Hexyl laurate

Emollient esters

JPE

TS

None listed

Solubiliser

Span™ 80 HP

Sorbitan Monooleate

Sorbitan esters

NF, Ph. Eur.

TS

2.33 MG

Permeation enhancer,
solubiliser

Span 20 HP

Sorbitan Monolaurate

Sorbitan esters

NF, Ph. Eur., JPE, ChP,
*DMF

TS

None listed

Permeation enhancer,
solubiliser

Smart science to improve lives™

*Ref: i) Lakshi et al. Int. Res. J. Pharm, 8(9), 9-17, (2017); ii) Dinda SC & Ratna JV. Indian J Pharm Sci, 68(3), 313-316, (2006); iii)
Cizinauskas V. Molecules, 22, 1536, (2017).
**Ref: US patent Application (#20050020552).
TG- Transdermal, Gel; TS- Transdermal, System, TF-ER- Transdermal Film, Extended release; TG-M- Transdermal gel, meteredDrug substance solubility platform
Excipient Hansen
solubility parameters
via SMILES

Experimental
maximum solubilityof drug substanceand in excipient

Excipient Hansen
solubility parametervia experiment

Drug inExcipient
Solubility
Prediction

Smart science to improve lives™

Solubility platform experimental drug
substance in excipientPlace active andexcipient in a vial

Centrifuge througha 0.45 µm filter

Mix at 25°C for
48 hours

Removesupernatant for
HPLC

Example actives tested• Anti-bacterials• Anti-cancer• Anti-fungals• Anti-virals• Cannabinoids• Decongestants• Hormones• Pain relief• Vitamins
Smart science to improve lives™

Typical excipients tested• PEGs• Polar liquids (Super Refined™ DMI, Super Refined™
DEGEE, Super Refined™ Propylene Glycol)• Oils• Esters• Long chain triglycerides• Fatty alcohols and acids• Surfactants• Water soluble• Oil solubleSolubility platform - example ofexperimental HSP
Acetaminophen solubility prediction•

Example fully theoretical HSP, HSP with improved excipient parameters with experimental data and fully
experimental maximum solubility data

Solubility
ranking

Fully theoretical
HSP

Experimental HSP for theoreticalsolubility prediction

Experimental maximum
solubility

1Super Refined™ PEG 300

Super Refined PEG 400

Super Refined PEG 400 (219.2 mg/g)

2

Super Refined Propylene Glycol

Super Refined CCMG 400

Super Refined PEG 300 (172.6 mg/g)

3Super Refined GTCC

Super Refined PEG 300

Super Refined Propylene Glycol (123.6
mg/g)

4

Super Refined P35 Castor Oil

Super Refined Propylene Glycol

Super Refined CCMG 400 (105.0 mg/g)

Smart science to improve lives™

Solubility platformSuper
Refined™
Crodamol
IPM

Menthol

Diclofenac
Diclofenac
Sodium
SodiumGlucosamine

HerbalHerbalExtracts
Extracts

Lidocaine
LidocaineSuper
Refined™
DEGEE

DA
DA
PharmaMethylMethylsalicylate
salicylate
Dimethicone

Indomethacin

Smart science to improve lives™

Super
SR
Refined™
Arlasolve
DMI
DMI

Crodamol
CrodamolChondroitin

Vitamins
Vitamins

NicotineSuper
Refined™
Oleic Acid

Iron

Super Refined™ DMIHIGHLY PURIFIED DIMETHYL ISOSORBIDE
50
40% Applied dose adsorbed

Features• Solvent for poorly soluble hydrophilic and hydrophobic
actives• Enhances formulation and API stability• Epidermal permeation enhancer• Improves spreading of viscous materials• Reduced cellular irritation

Stratum Corneum

30

Epidermis
Receptor Fluid20
100
Without Super Refined DMI

Expanding your permeation options with
Super Refined DMI, supporting data:
Penetrating solvent: Addition of just 10% Super Refined™
DMI to a formulation can result in a 15% increase in theamount of active delivered into the epidermis, and almost a
50% increase in active permeation into the stratum corneum.

Smart science to improve lives™

With 10% Super Refined DMI

O/W Emulsions

Topical delivery efficacy of a hydrophilic active in
two O/W formulations, one with and one without
Super Refined DMI.

Super Refined™ DMI
API stability• 1% w/w benzocaine in Super Refined DMI vs standard grade DMI• Samples incubated at 50oC for 9 weeks• Samples dissolved in acetonitrile for analysis• Detection method: HPLC at 0, 2, 4, 6, 9 weeks

Super Refined DMI 1

Super Refined DMI 2

Super Refined DMI 3

Standard DMI 1

Standard DMI 2

Standard DMI 3

API recovery (%) Super Refined™ DMI vs standard DMI; 1% Benzocaine at 9 weeks 50°C

Smart science to improve lives™

Super Refined DMI vs standard DMI samples;
1% Benzocaine at 9 weeks 50°C

Super Refined™ DEGEE
HIGH PURITY DIETHYLENE GLYCOL MONOETHYL ETHER

Features• Permeation enhancer• Excellent solubilising properties, ideal
for solubilising poorly water soluble APIs
• FDA IID Listed for topical and transdermal applications• Multi-compendial• Reduced impurity profile• Potential to reduce odour impact• Improved API and formulation stability

Smart science to improve lives™

Reduced impurity profile•

HS-GCMS was used to qualitatively analyse the volatile
impurity profiles of Super Refined DEGEE and a standard
compendial competitor material•

Impurity peaks were identified by matching retention times
and mass spectra of the identified peaks to standards andthose referenced in the NIST Research LibrarySuper Refined™ DEGEE
Expanding your permeation options with Super Refined DEGEE supporting data:
Permeation enhancer effect: Lidocaine• 0.8% solution of Lidocaine prepared in 15% Super Refined DEGEE, DEGEE and Super Refined DMI respectively,
in water• Skin permeation study using human cadaver skin
• Detection method: HPLC at 1-8h and 24h
MALDI MS imaging results

Super Refined DEGEE having stronger signal in the upper layers of the skin
Super Refined DEGEE

DEGEE

Super Refined DMI

Flux of Lidocaine in each permeation enhancer tested
Smart science to improve lives™

MALDI MS image of lidocaine in two sections obtained from
A: Super Refined™ DEGEE; B: DEGEE and
C:Super Refined™ DMI treated skin samples

Super Refined™ DEGEE
Permeation enhancer effect - simvastatin and raloxifene HCl (1% active gel)••••

1% Simvastatin and Raloxifene HCl gels containing Super Refined DEGEE, Super Refined DMI, competitor equivalent
to Super Refined™ DEGEE and DMSO as permeation enhancers
Concentrations tested: 0.5, 1, 2 and 5% w/w
Ex vivo skin permeation using pig skin as barrier medium
Detection method: HPLCSuper Refined
DEGEE

Super Refined
DMI

Super Refined
DEGEE

Super Refined
DMI

Super Refined DEGEE outperforms DMSO in terms of Simvastatin and Raloxifene HCl permeated into and through the skin. Super Refined DEGEE and Super
Refined DMI are both less damaging to the skin.
Smart science to improve lives™

Super Refined™ PEG 400
HIGHLY PURIFIED POLYETHYLENE GLYCOL 400
Features• Multi-compendial• Odourless, colourless viscous liquid• Extremely low impurity profile• Increases active stability• Low peroxide value and low residual EO• Effective when formulating with highly sensitive andunstable
API stability• Indomethacin was dissolved in standard
pharmaceutical grade PEG and Super Refined PEG
400• The samples were then subjected to accelerated
stability conditions and analysed by high performanceliquid chromatography (HPLC) to determine theamount of degradation of the active

Smart science to improve lives™

Super Refined PEG 400 consistently yielded a lower percent of impurities
over the length of 4-week study. By week 4, the impurity profile of Super
Refined PEG 400 was 33% less than the indomethacin dissolved instandard compendial PEG 400 NF.

Super Refined™ PEG 400
Excipient stability: peroxide value•••

Smart science to improve lives™

Low peroxide value in Super Refined PEG 400 for a 24week study duration as compared to standard PEG 400
High peroxides results in formaldehyde formation as
evident in standard PEG 400. Significant increase ascompared to Super Refined PEG 400
Formaldehyde eventually becomes formic acid.
Significantly higher levels in standard PEG 400 but barely
detectable in Super Refined PEG 400

Crodamol™ DA Pharma
DIISOPROPYL ADIPATE
Features• Provides excellent skin spreadability with no stickiness or tackiness• Enhanced API and formulation stability• Provides moisturising effect and improves skin texture
Stability

Hydrolytic stability

Crodamol DA Pharma

Crodamol DA Pharma

Time (hour)
Figure 1: recovery of lidocaine in Crodamol DA Pharma compared to standard
compendial grade of diisopropyl adipate over 30 days at 60°C

Smart science to improve lives™

Figure 2: acid value of Crodamol DA Pharma and JPE compendial competitive
product at 105°C for 160 hours

Claims for
products
We aim to help our customers
formulate medicines withclaims relevant to theircustomers, increasing thesuperiority of their productand brand.

Smart science to improve lives™

CASE STUDY

Muscle pain andtendinopathy“I want fast acting, long lasting pain relief
which I barely notice wearing”

Technical barriers

Smart science to improve lives™

•

Several excipients in combination required toachieve high drug solubility for long lasting effect•Drug prone to oxidation in excipients•

Some key solubilising excipients have a strong
unpleasant odour

CASE STUDY

Muscle pain andtendinopathy
Solutions

Smart science to improve lives™

•

Super Refined™ PEG 400, Super Refined
Castor Oil and Crodamol™ DA Pharma offer the
API solubility required when combined•

Crodamol DA Pharma is low in odour compared
to competitor diisopropyl adipate•

Super Refined Polysorbate 80 helps
compatibilise the formulation excipients•

Croda’s Super Refined excipients and Crodamol
DA Pharma have superior stability, protecting theformulation from drug degradation

CASE STUDY

Muscle pain andtendinopathy
Pack claims
Odourless

Fast acting pain relief
Less frequent application

Did you know that Croda offers a wide range of polar andnon-polar excipients in our Super Refined™ range?

Smart science to improve lives™

Super Refined™ Oleic Acid
HIGHLY PURIFIED OLEIC ACID
Features• Enhanced active and oxidative stability• Reduced skin irritation• Enhanced active membrane permeation

Percent intercellular leakage

Stability
Reduced cellular irritation - TEP results

Permeation efficacy - MALDI images

Oleic Acid
NF skinsamples32%
decrease

18
16
14
12
10
8
6
4
2
0

Super
RefinedOleic Acidskinsamples

Oleic Acid NF

Smart science to improve lives™

Super Refined Oleic Acid

CASE STUDY

Anti-inflammatory local administration
patch“The customer wants a patch that stays inplace”

Technical barriers

Smart science to improve lives™

•

Difficult to achieve balance of adhesive efficacy
and sufficient API solubility•

Difficult to solubilise required dose•

permeation enhancer required to get active past
the stratum corneum•

API prone to oxidation

CASE STUDY

Anti-inflammatory local administration
patch
Solutions

Smart science to improve lives™

•

Super Refined™ Hexyl Laurate compatibilises
the oil based solvents and permeation enhancers
with the adhesives and structural excipients•

Super Refined Oleic Acid offers API solubility andthe required permeation enhancement•

Super Refined Oleic Acid prevents API
degradation

CASE STUDY

Anti-inflammatory local administration
patch
Pack claims
Sticks and stays in place
Fast acting pain relief
Less frequent application

Did you know that Super Refined™ Oleic Acid
has been shown to be more “skin friendly” thanstandard oleic acid?

Smart science to improve lives™

Super Refined™ Isostearic Acid
•
•
•
•
•
•

Low viscosity
Good extensibility, light texture
Minimised skin irritation
Enhanced API and formulation stability
JPE compliance
FDA IID Listed

Detected impurities

Competitor A
Competitor B
Before Super Refining
Super Refined Isostearic Acid

Competitor A

Competitor B

Before Super Refining

Super Refined
Isostearic Acid

1

Methyl alcohol

lower alcohol

100

70

129

9

2

Ethyl alcohol

lower alcohol

100

97

250

36

3

Decanehydrocarbon

100

9

21

0

4

Propyl alcohol

lower alcohol

100

92

101

4

5

Tridecanehydrocarbon

100

2

5

0

6

Tetradecanehydrocarbon

100

4

9

0

7

Pentadecanehydrocarbon

100

11

11

0

8

Hexadecanehydrocarbon

100

6

4

0

9

Heptadecanehydrocarbon

100

38

17

3

Smart science to improve lives™

CASE STUDY

Anti-inflammatory local administration
patch“I want to put the patch where I need it, not justwhere it will stay on.”Technical barriers•

Smart science to improve lives™

Patch flexibility is poor due to required excipients
to solubilise sufficient API

CASE STUDY

Anti-inflammatory local administration
patch
Solutions•

Smart science to improve lives™

Moving from standard Isostearic Acid to Super
Refined™ Isostearic Acid significantly increased
patch flexibility

CASE STUDY

Anti-inflammatory local administration
patch
Pack claims
Sticks on joints - flexible effective patch

Did you know Super Refined™ Isostearic Acidcan be used as an even more oxidatively stable
alternative to Super Refined™ Oleic Acid?

Smart science to improve lives™

Super Refined™ IPM
ISOPROPYL MYRISTATE

Figure 1: Hydrolysis stability

Figure 2: GC Chromatograms of Super Refined IPM(a) Super Refined™ IPM, (b) competitor’s JPE grades, (c) competitor’s JPE grades

Very stable ester
Super Refined IPM has high purity compared withconventional grade of IPM. To demonstrate hydrolysis
stability, 1 wt % H2O was added in IPM and thesamples were heated under 120℃, air bubbling (5L/min.), using GC analysis to determine the IPM
purity, and the test was conducted at multiple time
points.

Low impurities

Smart science to improve lives™

Super Refined IPM exhibited significantly less impurities compared to thecompetitor grades. Super Refining process significantly reduced the amount of
isopropyl laurate (peak number 2), among other impurities.

CASE STUDY

Antipsychotic systemadministration patch“We need long lasting persistent effects
from each application”

Technical barriers

Smart science to improve lives™

•

Long term effectiveness of each patch is API
solubility limited•

Need solubility enhancers with good patch
excipient compatibility

CASE STUDY

Antipsychotic systemadministration patch
Solutions

Smart science to improve lives™

•

Combination of Super Refined™ Sesame Oil andSuper Refined IPM maximise API solubility•

Combination does not interfere with patch
excipients and materials

CASE STUDY

Antipsychotic systemadministration patch
Pack claimsLong lasting application

Did you know that Croda offer a wide range ofSuper Refined™ vegetable oils and ester oils?

Smart science to improve lives™

Why work with us?
Create tailored
excipient solutions
directly in partnershipwith our scientists.

Tackle your stability challenges
with unparalleled purity excipients
across all administration routes.

Formulate andtroubleshoot fasterby working with ourscientific experts during
your development.

Smart science to improve lives™

Prioritisesustainability
and integrity bychoosing Croda.

Croda Pharma

Thank you!

Non-warranty
The information in this publication is believed to be accurate and is given in good faith, but no representation or warranty as to its completeness or accuracy is made. Suggestions for uses or applications are only opinions.
Users are responsible for determining the suitability of these products for their own particular purpose. No representation or warranty, expressed or implied, is made with respect to information or products including, without
limitation, warranties of merchantability, fitness for a particular purpose, non-infringement of any third-party patent or other intellectual property rights including, without limit, copyright, trademark and designs. Any
trademarks identified herein are trademarks of the Croda group of companies. ©2022 Croda International Plc

Smart science to improve lives™

10/22 HTCMP234v2 EN