1	CYCLODEXTRINS
2	CONTENTS Characterization of cyclodextrins Performance of complexes of cosmetic actives: Gamma-Cyclodextrin-Complex of Retinol, Vitamin A Alpha-Cyclodextrin-Complex of Linoleic acid, „Vitamin F“ Alpha-Cyclodextrin-Complex of Linoleic acid, Biotin Beta-Cyclodextrin-Complex of Tea Tree Oil, Essential Oil Release behavoir of complexes Analysis of cyclodextrin-complexes Applications Summary
3	HISTORY OF CYCLODEXTRINS First reference to cyclodextrins was made by Villiers in 1891. He isolated a small amount of a crystalline substance from a culture medium of Bacillus amylobacter on a medium of potato starch. Villiers named his crystalline product “cellulosine” owing to its alleged similarity to cellulose. He even then observed the existence of different kinds of “cellulosine”.
4	WHAT ARE CYCLODEXTRINS ? Cyclic oligosaccharides with defined ring size Subunits: D-glucose (dextrose) Water soluble, non reducing
5	COST-EFFECTIVE PRODUCTION OF CYCLODEXTRINS
6	THE STRUCTURE OF CYCLODEXTRINS
7	CHARACTERISTICS OF CAVAMAX^® CYCLODEXTRINS non reducing, chiral, cyclic oligosaccharide very stable in alkaline solution (pH up to 14) hydrolysis in acidic media (pH < 3) thermally stable < 200 °C
8	COMPLEXATION AS A SYSTEM OF DYNAMIC EQUILIBRIA
9	INCLUSION COMPLEX FORMATION: RETINOL-CD
10	CAVAMAX^® W8/RETINOL–COMPLEX: MOLECULAR MODEL
11	CYCLODEXTRINS AVOID DETERIORATION OF LIPOPHILIC ACTIVES
12	PH RANGE 16% of Retinol-Complex has degraded at pH 7, however 70% of Retinol-Complex at pH 4 after 8 weeks at 40°C
13	RETINOL-COMPLEX IN EMULSION 16% of Retinol-Complex has degraded at pH7 after 8 weeks at 40°C, however 51% of uncomplexed Retinol
14	PREPARATION OF AN EMULSION Preparation of an emulsion with CAVAMAX^ÒW8/Retinol-Complex Preparation of Retinol-Complex-Dispersion Disperse 1-10w/w% of CAVAMAX^ÒW8/ RETINOL-COMPLEX as powder in water by stirring for 10-30 minutes at 20-40°C. W/O Emulsions The water dispersion of Retinol-Complex should be added to lipophilic ingredients and homogenised for approx.10 minutes at 20-50°C. O/W Emulsions Lipophilic ingredients can be added to the water dispersion of Retinol-Complex and homogenised for approx.10 minutes at 20-50°C.
15	RETINOL ANALYSIS BY HPLC
16	HPLC PARAMETERS AND GENERAL PREPARATION METHOD
17	PREPARATON OF A SKIN CARE CREAM
18	RECOMMENDATION, CALCULATION AND PREPARATION
19	INCLUSION COMPLEX FORMATION: LINOLEIC ACID C18:2-CD
20	CYCLODEXTRINS AVOID DETERIORATION OF LINOLEIC ACID C18:2 UNDER UV A/B-RADIATION
21	ALPHA CYCLODEXTRIN COMPLEX OF LINOLEIC ACID C18:2
22	OXIDATION OF LINOLEIC ACID C18:2 IN EMULSIONS
23	CYCLODEXTRIN IMPROVES WATER SOLUBILITY OF LIPOPHILIC VITAMIN (Biotin)
24	DETERIORATION OF TEA TREE OIL
25	ODORLESS TEA TREE OIL-COMPLEX IN LIPOPHILIC COSMETIC Off-odor of tea tree oil uncomplexed and complexed in lip balm was determined by SPME-Analysis (SolidPhase-MicroExtraction)
26	CAVAMAX® W7/TEA TREE OIL–COMPLEX IN COSMETIC FORMULATIONS
27	GENERAL PREPARATION METHOD The following is an example calculation and preparation of a transparent lip balm with CAVAMAX^®W7-TEA TREE OIL-COMPLEX. Calculation 10.6g Tea Tree Oil are related to 100g complex, 1g Tea Tree Oil related to x g complex 100g x 1g = 9.46g 10.6g Preparation 1) Heat all ingredients of phase A) in a water bath under slow stirring to 80°C 2) Add phase B) under intense stirring for 5 minutes 3) Pour into moulds.
28	RELEASE OF COMPLEXED TEA TREE OIL IN GEL Off-odor of tea tree oil in Copolymer / 98% H2O uncomplexed and complexed
29	CYCLODETRIN-COMPLEX AND HUMIDITY Recurrent release of 0.5% Bergamot Oil on non woven controlled by CAVASOL^® W7 M Complex and triggered by water
30	PREPARATION OF AN ANTIPERSPIRANT CREAM
31	PREPARATION Procedure Preparation: Heat phase A to 60-65°C under stirring. Heat phase B to 60°C. Add A to B while homogenizing. Cool down under stirring. At 40°C add phase C.Cool down to room temperature under stirring. Selection of complexes of cosmetic actives useful for deo and antiperspirant formulation: Complex Function of active CAVAMAX^® W7 / FARNESOL COMPLEX Anti-Microbial (Occurrence: Essential Oils) CAVAMAX^® W7 / MENTHOL COMPLEX Cooling Agent CAVAMAX^® W7 / TEA TREE OIL COMPLEX Anti-Microbial (Essential Oil) CAVAMAX^® W7 / Perfume Oil Complex Fragrance
32	RELEASE BEHAVOIR OF COMPLEXES
33	ANALYSIS OF CYCLODEXTRIN-COMPLEXES Analysis Qualitative evaluation by sensory test Release of complexed fragrances upon wetting Quality of Complex Solubility of complex (free cyclodextrin) DSC (free solid substances) Stability testing of complex and in cosmetic formulations by HPLC SPME, OFF-ODOUR-Detection Content of guest substance HPLC, NMR, GC
34	PREPARATION Preparation of Retinyl Palmitate-Complex Dispersions: Disperse 1-10 w/w% of CAVAMAX^ÒW8 / RETINYL PALMITATE-COMPLEX as powder in water by stirring for 10-30 minutes at 20-40°C. W/O Emulsions The water dispersion of RETINYL PALMITATE-Complex should be added to lipophilic ingredients and homogenised for approx.10 minutes at 20-50°C. O/W Emulsions Lipophilic ingredients can be added to the water dispersion of RETINYL PALMITATE-COMPLEX and homogenised for approx.10 minutes at 20-50°C. Retinyl Palmitate analysis by HPLC Preparation of retinyl palmitate Standard Approx. 10mg of Vitamin-A-palmitate 1.7 Mio. I.E./g (supplier BASF) is dissolved in a mixture of N,N-Dimethylformamide / Hexane (90/10 v/v) in a 100ml brown glass or aluminium foil covered volumetric flask to avoid exposure to light. The solution is sonicated for 5 minutes.
35	COMPLEX IN EMULSION Retinyl palmitate in CAVAMAX^® W8 / RETINYL PALMITATE–COMPLEX The samples should be prepared in glassware covered with Al foil or in brown coloured flasks. Approx. 15mg of the complex as a powder is dissolved in a mixture of N,N-Dimethylformamide / Hexane (90/10 v/v) in a 10 mL volumetric flask. After homogenisation for 5 minutes in an ultrasonic bath, the solution is analysed by HPLC to determine the content of retinyl palmitate in the complex. Retinyl palmitate as CAVAMAX^® W8 / RETINYL PALMITATE COMPLEX in emulsion Approx. 200mg of the emulsion is dispersed in the mixture of N,N-Dimethylformamide and Hexane (90/10 v/v) in a 10 mL volumetric flask and homogenised in an ultrasonic bath for 10 minutes. The sample is then analysed by HPLC.
36	HPLC-PARAMETERS AND GENERAL PREPARATION METHOD HPLC-parameters: Column: Nucleosil C 18 100-7 mm; L.250 mm; ID 4 mm, Mobil phase: Methanol/ Hexane (90/10 v/v) Flow: 4.0 mL/min Temperature: 30°C Detection: UV at 325 nm Injection volume: 10µl General preparation method The following is an example calculation and preparation of a cosmetic formulation with CAVAMAX^ÒW8 / RETINYL PALMITATE-COMPLEX. Preparation temperature of >50°C for more than 15 minutes after the addition of CAVAMAX^ÒW8 / RETINYLPALMITATE-COMPLEX should be avoided.
37	PREPARATION OF A SKIN CARE CREAM WITH RETINYL PALMITATE
38	CAVAMAX^ÒW8 / RETINYL PAMITATE-COMPLEX IN COSMETIC FORMULATIONS Recommendation: Emulsions with CAVAMAX^ÒW8/ RETINYL PALMITATE–COMPLEX should be prepared at pH 7 Calculation: 14.8 g retinyl palmitate are related to 100g complex, 0.55g retinyl palmitate (10.000I.U. /g) related to x g complex 100g x 0.55g = 3.7g 14.8g Preparation: 1) A suspension of water and CAVAMAX^ÒW8 / RETINYL PALMITATE-COMPLEX is stirred for 15 minutes at 40°C. Phase A is completed by the addition of Disodiumhydrogenphosphate dodecahydrate. 2) Phase B is stirred at 70°C. 3) Add phase A to phase B under intense stirring for about 10 minutes. 4) Add Phase C and homogenise below 40°C.
39	APPLICATION TO CONSUMER PRODUCTS
40	SUMMARY: TRULY THE WORLD´S SMALLEST BEAUTY CASE
41	QUESTIONS (1) What are the benefits of cyclodextrins? What are cyclodextrin complexes? Which cosmetic ingredients are suitable for complexation with cyclodextrins? Which cyclodextrins or complexes are already used in cosmetics? How are cyclodextrin complexes used in cosmetic formulations? How are the complexes added to emulsions? What method should be avoided for the preparation of emulsions with cyclodextrin complexes? What are the success factors of HPLC-Analyses of cyclodextrin complexes or emulsions containing complexes?
42	ANSWERS (1) Stabilization of sensitive substances to avoid deterioration by oxidation, light, temperature; Enhancement of water solubility; Reduction of unpleasant odor; Controlled release of the guest substance e.g. by humidity; Reduction of volatility e.g. essential oils 2) The smallest beauty case of the world is a cyclic sugar. The unique structure of this cyclodextrins enables them to form host-guest or inclusion complexes with a variety of materials. Lipophilic subastances are placed in the lipophilic interior of the cyclodextrin and hold by “Van der Waals-forces”. 3) Lipophilic substances like oil soluble vitamins, PUFA´s, fragrances or essential oils perform very well in the lipophilic cyclodextrin cavity. Hydrophilic actives like dihydroxaceton gives with CD´s a 2-component-system, which are related to the properties of a physical mixture.
43	ANSWERS (2)
44	ANSWERS (3) The complex as powder or granulate should be never added to finished products like creams, because large particle size of complexes are responsible for a sandy feeling in finished products and bad dispersion. Only homogen samples should be analysed. The particles of the complex will decrease during dispersion in water. It should be avoided to add complexes of guest material like retinol to an emulsion with a pH<7. HPLC-method useful for the guest material of the complex like a cosmetic active, has zu be modified to be useful for the guest-host-complex. The complex have to be soluble in the solvent. The cream samples containing a complex have to be pretty soluble in the used solvent to extract the total amount of guest material out of the complex.
45	WACKER: YOUR PARTNER FOR CYCLODEXTRINS