Simulsol

SEPPIC
Pharmaceutical and Nutraceutical Offer
An affiliate of
SEPPIC, Air Liquide subsidiary
 Air Liquide, French group, world leader in gases for
industrial applications and healthcare
 Air Liquide supplies to food and pharmaceutical
industries with N2, CO2, O2…
 2010 turnover : 13,5 billions €
 1 million customers worldwide
 9 360 patents and 2 500 inventions
 42 300 employees
 Member of Air Liquide Group since 1986
 2011 turnover: 260 millions €
 Industrial sites: Castres - France,
Shanghai - China
 3 500 m2 of laboratories, research budget: 8 millions €,
more than 100 researchers, 140 patents in 10 years
 630 employees
 Commercial subsidiaries and offices: Germany, Italy, United
Kingdom, USA, China, Singapore, Brazil, India, Colombia
 3 Customer Demonstration Centers: France, China, US
Commercial activities
Cosmetic
Pharmacy & Nutrition
Excipients
+ Surfactants
+ Thickeners
Actives
+ Moisturizers
+ Smoothers
Excipients
+ Emollients
+ Emulsifiers
+ Preservatives
+ Free rad. scavengers
+ Anti wrinkle
Adjuvants for Vaccine & Injectable
+ Injectable surfactants
+ Adjuvants for vaccines
+ Surfactants
+ Emulsifiers-Solubilizers
+ Film-coatings + Binders-Fillers
Actives and ingredients
+ Mineral salts
+ Stevia
+ Nutritional ingredients
Industrial specialities
+ Functional additives
+ Surfactants for coating, inks
Oil field, Paper, Glass Frosting
Pharmacy & Nutrition activity
SEPPIC, renowned specialist of excipients, actives and ingredients
dedicated to pharmaceutical, nutraceutical and food applications
Customer
applications
Solid oral dosage forms
(excipients)
SEPPIC Solutions & Services
Excipients
Film-coatings
Binders for compression
Liquid & semi-solid oral
dosage forms
(excipients)
Topical dosage forms
(excipients)
Actives – Ingredients
(all forms)
Bioavailability
enhancers
Surfactants
Disintegrants
Actives - Ingredients
Nutritional actives
Mineral salts
Sweeteners
Galenic expertise
Application laboratory
Tests and product
developments in
partnership
Process optimisation
Encapsulation technology
Trainings:
Sepischool-Dermoschool
Regulatory support
SOLID ORAL DOSAGE FORMS
OFFER
Solid oral dosage forms
LIQUID & SEMI-SOLID
ORAL DOSAGE FORMS
OFFER
Solubilizers & Emulsifiers (1/4)
Solubilizers
non ionic surfactants
 Use: alone or with a co-solubilizer to enhance solubility of poorly or non
soluble in water active
 Formulation of syrups, suspensions but also tablets, capsules, creams…
Montanox, Polysorbates
- Hydrophilic surfactants, soluble or dispersible
in water
- Stable in acidic or alkaline media (pH: 4 to 10)
and in presence of electrolytes
- Excellent solubilizers of essential oils
Simulsol, Castor oil based solubilizer
- Soluble or dispersible in water and
vegetable oils
- Stable in acidic or alkaline media and
in presence of electrolytes
- Often used for hot solubilisation
Examples of solubilized actives
Actives
Fenofibrate,
Ibuprofen
Ibuprofzne,
Carbamazepine,
Verapamil,
Diclofenac
Paclitaxel,
Diclofenac
Tramadol,
Progesterone
Carbamazepine,
Diclofenac,
Ciclosporine
Advised solubilizer
Montanox 20 PHA PREMIUM
Montanox 80 PHA PREMIUM
Simulsol 1285 PHA
Simulsol 1292 PHA
Simulsol 4000 P
Solubilizers & Emulsifiers (2/4)
Emulsifiers
non ionic surfactants
 Simultaneous use of 2 surfactants: one hydrophilic and the other lipophilic,
to formulate very stable emulsions
 Optimisation of emulsion formulation by testing (through experiments)
various concentrations of each surfactant
 Formulation of syrups, suspensions but also creams, ointments…
Montane, Sorbitan esters
Montanox, Polysorbates
- Lipophilic surfactants to form
W/O emulsions
- Hydrophilic surfactants to form O/W emulsions
- Soluble and dispersible in oil
Simulsol, Ethoxylated fatty acids
- Hydrophilic surfactants to form
very stable O/W emulsions
- Soluble or dispersible in water
- Intended for emulsions containing
low proportions of oil phase
- Soluble and dispersible in water and organic
solvents
Solubilizers & Emulsifiers (3/4)
Regulation : solubilizers and emulsifiers
 SEPPIC surfactants are ISO 9001 certified
PREMIUM
 Strong demand from the pharmaceutical industry to have excipients in
conformity with GMP guidelines. SEPPIC has developed a new surfactant
range – PHA PREMIUM – that fully complies with future excipients GMP
requirements, outlined in PQG-IPEC guideline
Quality
DF
PHA PREMIUM
PPI
Requirements
+ Dioxan Free
+ Cosmetic grade
+ Statistical control of EP conformity
+
+
+
+
+
+
+
+
+
+
+
GMP
Conformed to EP – USP
Cleaning of vessels with the same product family
Suppliers audited
Manufacturing process controlled by quality assurance
Usable injectable product
GMP
Conformed to EP – USP – JP
Cleaning validation
Final filtration and packaging in controlled atmosphere
Microbiological control and endotoxins analyses
Solubilizers & Emulsifiers (4/4)
Chimical name (EO)
Function
Quality
Montane 20
Sorbitan laurate
Lipophilic emulsifier
DF – PHA PREMIUM – PPI
Montane 60
Sorbitan stearate
Lipophilic emulsifier
DF – PHA PREMIUM*
Montane 80
Sorbitan oleate
Lipophilic emulsifier
DF – PHA PREMIUM – PPI
Montane 85
Sorbitan trioleate
Lipophilic emulsifier
DF – PHA
Montanox 20
Polysorbate 20
Montanox 60
Polysobate 60
Montanox 80
Polysobate 80
Mono-oleate (20)
Hydrophilic emulsifier
Solubilizer
Hydrophilic emulsifier
Solubilizer
Hydrophilic emulsifier
Solubilizer
Simulsol M 45
Macrogol stearate (8)
Hydrophilic emulsifier
PHA
Simulsol M 52
Macrogol stearate (40)
Hydrophilic emulsifier
PHA
Simulsol 2599
Macrogol oleate (10)
Hydrophilic emulsifier
PHA
Solubilizer
PHA
Solubilizer
PHA
Solubilizer
PHA
Mono-laurate (20)
Mono-stearate (20)
Macrogol glycerol
ricinoleate (50)
Macrogol glycerol
Simulsol 1292
hydroxystearate (25)
Polyoxyl-40-hydrogenated
Simulsol 4000 P
castor oil (40)
Simulsol 1285
DF: cosmetic grade
DF – PHA PREMIUM – PPI
DF – PHA PREMIUM* – PPI
DF – PHA PREMIUM – PPI
PPI: injectable grade
* available in june 2012
Liquid & semi-solid oral forms
Rebaten
&
Steviten
Montane
Sorbitan
esters
Stevia
Extract
Montanox
Polysorbates
Purolite
Simulsol
IER
Ethoxylated
macrogols
Emulsifiers
Solubilizers
Sepitrap™
Solubilizers for
Direct Compression
Taste
masking
TOPICAL DOSAGE FORMS
OFFER
Solubilizers & Emulsifiers (1/6)
Solubilizers
non ionic surfactants
 Use: alone or with a co-solubilizer to enhance solubility of poorly or non
soluble in water active and thus to improve its bioavailability
 Formulation of syrups, suspensions but also tablets, capsules, creams…
Montanox, Polysorbates
- Hydrophilic surfactants, soluble or dispersible
in water
Examples of solubilized actives
Actifs
Solubilisant conseillé
- Stable in acidic or alkaline media (pH: 4 to 10)
and in presence of electrolytes
Kétoconazole
Montanox 60 PHA PREMIUM
- Excellent solubilizers of essential oils
Diclofenac
Montanox 80 PHA PREMIUM
Diclofenac
Simulsol 1285 PHA
- Soluble or dispersible in water and
vegetable oils
Progesterone
Simulsol 1292 PHA
- Stable in acidic or alkaline media and
in presence of electrolytes
Diclofenac
Simulsol 4000 P
Simulsol, Castor oil based solubilizers
- Often used for hot solubilisation
Solubilizers & Emulsifiers (2/6)
Emulsifiers
non ionic surfactants
 Simultaneous use of 2 surfactants: one hydrophilic and the other lipophilic,
to formulate very stable emulsions
 Optimisation of emulsion formulation by testing (through experiment)
various concentration of each surfactant
 Formulation of creams, ointments but also syrups, suspensions …
Montane, Sorbitan esters
Montanox, Polysorbates
- Lipophilic surfactants to form
W/O emulsions
- Hydrophilic surfactants to form O/W emulsions
- Soluble and dispersible in oil
Simulsol, Ethoxylated fatty acids
- Hydrophilic surfactants to form
very stable O/W emulsions
- Soluble or dispersible in water
- Intended for emulsions containing
low proportions of oil phase
- Soluble and dispersible in water and organic
solvents
Solubilizers & Emulsifiers (3/6)
Regulation : solubilizers and emulsifiers
PREMIUM
 SEPPIC surfactants are ISO 9001 certified
 Strong demand from the pharmaceutical industry to have excipients in
conformity with GMP guidelines. SEPPIC has developed a new surfactant
range – PHA PREMIUM – that fully complies with future excipients GMP
requirements, outlined in PQG-IPEC guideline
Quality
DF
PHA PREMIUM
PPI
Requirements
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Dioxan Free
Cosmetic grade
Statistical control of EP conformity
GMP
Conformed to EP – USP
Cleaning of vessels with the same product family
Suppliers audited
Manufacturing process controlled by quality assurance
Usable injectable product
GMP
Conform to EP – USP – JP
Cleaning validation
Final filtration and packaging in controlled atmosphere
Microbiological control and endotoxins
Solubilizers & Emulsifiers (4/6)
Chimical name (EO)
Function
Quality
Montane 20
Sorbitan laurate
Lipophilic emulsifier
DF – PHA PREMIUM – PPI
Montane 60
Sorbitan stearate
Lipophilic emulsifier
DF – PHA PREMIUM
Montane 80
Sorbitan oleate
Lipophilic emulsifier
DF – PHA PREMIUM – PPI
Montane 85
Sorbitan trioleate
Lipophilic emulsifier
DF – PHA
Montanox 20
Polysorbate 20
Montanox 60
Polysobate 60
Montanox 80
Polysobate 80
Mono-oleate (20)
Hydrophilic emulsifier
Solubilizer
Hydrophilic emulsifier
Solubilizer
Hydrophilic emulsifier
Solubilizer
Simulsol M 45
Macrogol stearate (8)
Hydrophilic emulsifier
PHA
Simulsol M 52
Macrogol stearate (40)
Hydrophilic emulsifier
PHA
Simulsol 2599
Macrogol oleate (10)
Hydrophilic emulsifier
PHA
Solubilizer
PHA
Solubilizer
PHA
Solubilizer
PHA
Mono-laurate (20)
Mono-stearate (20)
Macrogol glycerol
ricinoleate (50)
Macrogol glycerol
Simulsol 1292
hydroxystearate (25)
Polyoxyl-40-hydrogenated
Simulsol 4000 P
castor oil (40)
Simulsol 1285
DF: cosmetic grade
DF – PHA PREMIUM – PPI
DF – PHA PREMIUM – PPI
DF – PHA PREMIUM – PPI
PPI: injectable grade
* available in june 2012
Solubilizers & Emulsifiers (5/6)
Chimical name (EO)
Function
Quality
Simulsol P4
Macrogol lauryl ether (4)
Hydrophilic emulsifier
PHA
Simulsol P23
Macrogol lauryl ether (23)
Hydrophilic emulsifier
PHA
Simulsol 58
Macrogol cetostearyl ether (20)
Hydrophilic emulsifier
PHA
Simulsol 68
Macrogol cetostearyl ether 22)
Hydrophilic emulsifier
PHA
Simulsol 165 PHA, glucerol-based surfactant combined with a
polyoxyethylenated emulsifier
 Intended for use in acidic or electrolyte-containing O/W emulsion
 Used alone: as self-emulsifier wax:
Concentration
5%
10%
15%
20%
25%
Consistency
Fluid milk
Milk
Thick milk
Liquid cream
Thick cream
Stability
Good
Excellente
Excellente
Excellente
Excellente
+ disperses easily in water
+ acts as emulsifier, effective opacifying
agent and gelling agent
Solubilizers & Emulsifiers (6/6)
Montane, Montanox, Simulsol, valuable surfactants to simplify the
choice of emulsifying systems in the development of the various formulations
that can be used in pharmaceuticals
Ointments, creams , gels, lotions, onguents…
Oil/Water emulsions
SIMULSOL™ 165 PHA
MONTANE™ 60 PHA PREMIUM /MONTANOX™ 60 PHA PREMIUM
MONTANE™ 60 PHA PREMIUM/SIMULSOL™ 58 PHA
SIMULSOL™ P 4 PHA/SIMULSOL™ P 23 PHA
SIMULSOL™ M 52 PHA/MONTANE™ 60 PHA
Water/Oil emulsions
MONTANE™ 80 PHA PREMIUM, MONTANE™ 85 VG PHA
Lipophilic anhydrous ointments
MONTANE™ 80 PHA PREMIUM
MONTANE™ 85 VG PHA
Hydrophilic anhydrous ointments
SIMULSOL™ 165 PHA
Topical forms
Solubilizers
Emulsifiers
Montane
Sorbitan Esters
Montanox Polysorbates
INNOVATION in formulation
emulsion – gel – cream
Simulsol
Ethoxylated macrogols
Sepineo P600 Co-polymer
Emulsifier – thickener – stabilizer
Sepineo SE 68 APG self-emulsifier
Foaming agents
Amonyl Betaine amphoteric derivatives
Oramix APG, non-ionic
Foaming agent
Foaming agent for antiseptic formulation
 Solubilisation of antimicrobial active agents without altering their properties
 Use in antiseptic products and as foaming agent in hydro-alcoholic gel, shampoo
and other antiseptic products
Amonyl, Betaine derivatives
Oramix, APG: AlkylPolyGlucoside
- Amphoteric foaming agent
- Non-ionic foaming agent
- Soluble in water, very stable and low
sensitivity to pH variation to form a
stable foam
- Can be easily combined with other cationic,
anionic ornon-ionic agents
Chemical name
Oramix NS 10
Decylglucoside
Amonyl 265 BA
Betaine Cocoalkyldimethyl
Amonyl 380 BA
Betaine Cocoamidopropyl
Amonyl 440 NI
Betaine Cocoamidopropyl
Amonyl 675 SB
HydroxySulfobetaine
Cocoamidopropyl
Foaming aptitude
Cleansing
properties
Very good, develops
good volume of foam
Very good
Good, resistant to high
content in electrolyte
Good &
bacteriostatic
properties
-
-
Stable, resistant to high
content in electrolyte
Good
Sepineo P600 (1/2)
SEPINEO™ P600, 3 in 1 polymer, to formulate instantly non tacky gels or
creams showing non greasy and light texture
 Thickening power, in aqueous or organic medium over a large pH range
 Stabilizing power, not sensitive to shear, use at low concentration to stabilize and
maintain viscosity of oil/water emulsions
 Emulsifying polymer, no HLB calculation, to obtain an innovative texture gel-cream
 Ready to use liquid form, easy to handle at room temperature, no neutralization, no
rehydratation
 DMF type IV
+ Water
+ Water
+ Oil
GEL
aqueous, hydro-alcoholic,
with solvents…
GEL - CREAM
Emulsions with
Different oily phases
Sepineo P600 (2/2)
SEPINEO™ P600, simple process at room temperature
 Water/oil emulsion, formulated in indirect mode with an intern phase up to 90%
 Gel, single phase for hydrophilic actives
 Hydro-alcoholic gel, ethanol up to 70%, often used to increase API solubility and
permeability
 Anhydrous gel, support dedicated to water sensitive API
 Gel-cream, 2 phases system (up to 40% of lipophilic phase) without emulsion
process at room temperature
 Increase compliance:
+ light texture
+ non sticky
+ non greasy…
Technical presentation
Sepineo SE 68
SEPINEO™ SE 68, AlkylPolyGlucoside (APG) self-emulsifier promoting very
stable oil in water emulsion
 Self-emulsifier dedicated to form emulsion with no HLB calculation and without specific
addition of fatty phase. It is possible to achieve anhydrous emulsion with water sensitive
actives
 Innovative texture with pronounced rheo-fluidity, hence favouring a uniform and
homogenous spreading of API at the skin surface  improve compliance
 Natural polymer - non ethoxylated - with excellent skin tolerance, stable over a wide
range of pH and with electrolytes
 Wide compatibility with fatty phases, thanks to its glucolipid structure
 Emulsion stable with various fatty phase concentrations, up to 60%
 DMF type IV
Sepineo SE 68 is able to
promote liquid crystals,
regardless of the nature of oil
phase: esters, silicon oils,
vegetable oils…
Technical presentation
Lamellar bi-layers obtained with SEPINEO SE 68 fully surround the oil droplet and
form a stable, rigid shell preventing coalescence
ACTIVES – INGREDIENTS
OFFER
Actives and Ingredients
Mg Ca
Fe
CERAMOSIDES
Na
PROLIVOLS
K
Mn Cu
Zn
Li
Amino
Acids
Natural
Nutritional
Actives
AROLIA
Mineral Salts
PROVINOLS
EXTRAMEL
GIVOMAG (API and nutritional GIVOCAL
Magnesium
Glycerophosphate
grades)
Calcium
Glycerophosphate
Calci-press
Destab Descote
Heavy MgO
REBATEN
&
STEVITEN
Other pharmaceutical actives
Anti-carie
Anti-fungal
Intestinal antiseptic
Rubefacients
Stevia Extract
natural
sweeteners
Nutritional actives
Antioxidant
Antiage
Dermonutrition
EXTRAMEL
Encapsulated melon
Superoxide dismutase
AROLIA
Açai extract
Polyphenols
PROVINOLS
Red wine extract
Polyphenols
PROLIVOLS
Olive extract
Polyphenols
GIVOCAL
Calcium
Glycérophosphate
GIVOMAG
Magnesium
Glycerophosphate
REBATEN 97%
Stevia extract
Rebaudioside A
CERAMOSIDES
Wheat extract
Ceramides and DGDG
Other minerals:
Cu, Zn, Fe, Mn, K
Cardiovascular
health
& Lipid
Metabolism
Stress, fatigue
&
Cognitive
health
Sport
nutrition
& vitality
Weight
control
Slimming
Bone health
Menopause
Nota
Les seules spécifications analytiques garanties sont celles figurant dans le bulletin d’analyse fourni à chaque livraison de produit.
SEPPIC* ne donne aucune garantie, implicite, expresse ou légale, autre que la garantie limitée décrite ci-dessus, pour le produit objet de ce document. Sans préjudice des
dispositions qui précèdent, SEPPIC* ne donne aucune garantie quant à la qualité loyale et marchande du produit ou à son aptitude à un usage particulier. L’utilisation
et/ou la vente du produit, seul ou associé à d’autres marchandises, se feront sous la seule responsabilité du client. Les informations contenues dans ce document sont
fournies gracieusement, et sont données à titre indicatif ; elles sont basées sur l’état des connaissances de SEPPIC* relatives au produit à cette date et sont données de
bonne foi. Ces informations sont destinées à des personnes ayant une compétence technique et les utilisant à leurs risques et périls. Etant donné que l’utilisation de ces
informations est en dehors du contrôle de SEPPIC*, SEPPIC* ne donne aucune garantie, implicite ou expresse, et n’assume aucune responsabilité quant à l’utilisation de
ces informations. En particulier, le client devra vérifier qu’il ne contrevient pas à des brevets existants.
* SEPPIC étant :
SEPPIC S.A.
22 Terrasse Bellini
92806 Puteaux
FRANCE
Tel. : +33 (0)1 42 91 40 00
[email protected]
Head Office
75, quai d'Orsay
75007 Paris
FRANCE
SEPPIC Japan Office
Air Liquide Japan's office
Granpark Tower 3-4-1 Shibaura
Minato-ku, Tokyo 108-8509
JAPAN
Tel : +81 3 6414 6725
[email protected]
SEPPIC Italia Srl
Via Quarenghi 27
20151 Milano
ITALY
Tel : +39 02 38009110
[email protected]
SEPPIC UK Ltd
50, Salisbury Road
PO Box 338 - Hounslow - TW4 6SH
ENGLAND
Tel. : +44 208 577 8800
[email protected]
SEPPIC Inc.
30, Two Bridges Road, suite 210
Fairfield,
New Jersey 07004-1530
USA
Tel. : +1 973 882 5597
[email protected]
SEPPIC Pologne Office
CCIF
Ul. Widok 8
00-023 Varsovie
POLAND
Tel : +48 22 690 68 73
[email protected]
SEPPIC Brasil
Rua Libero Badaro, 182
8° andar - Centro
01008-000 Sao Paolo SP
BRAZIL
Tel : +55 11 3242 3911
[email protected]
SEPPIC Gmbh
Von-der-Wettern-STR.27
51149 Köln
GERMANY
Tel. : +49 (0) 2203-89830-20
[email protected]
SEPPIC Colombia SAS
Calle 71 N°10-40
Edificio Orbe 71 of 401
Bogota
COLOMBIA
Tel : +(571) 702 44 48
[email protected]
SEPPIC Asia Singapore
SEPPIC Dubaï Office
120 Lower Delta Road # 13 – 11
Dubaï Airport Free Zone
Cendex Center
West Wing 4 B, Suite 144
Singapore 169208P.O. Box _ 54638, Po Box 54638 Dubaï
SINGAPORE
UAE
Tel : +65 6278 6711
Tel : +971 4 239 5565
[email protected]
[email protected]
SEPPIC Chine
Room 510 Jin Tai Bulding
58 South Mao Ming Road
Shanghai 200020
CHINA
Tel : +86 (21) 64 66 01 49
[email protected]
SEPPIC Mumbai
B-110, Knox Plaza
MindSpace, Off Chincholi bunder rd
Malad (W) Mumbai – 400064
INDIA
Tel : +91 22 42726464
[email protected]
5640/GB/02/November 2011