Selecting the Primary Selecting the Primary Emollient to Enhance the Emollient to Enhance the Vitamin E- Acetate Skin Vitamin E- Acetate Skin

PenetrationPenetrationJOSHITA DJAJADISASTRAJOSHITA DJAJADISASTRA 1, Sasanti Tarini , Sasanti Tarini 2, Sugiyono, Sugiyono1

1Department of PharmacyDepartment of PharmacyFaculty of Mathematics and Sciences, University of Indonesia Faculty of Mathematics and Sciences, University of Indonesia

2 School of Pharmacy, Research Group of Pharmaceutics – Institute Technology of Bandung Email : joshita_d@yahoo.comEmail : joshita_d@yahoo.com

OUTLINEOUTLINE

• INTRODUCTION: SUNLIGHT – FREE RADICALS – DAMAGE ON HUMAN SKIN

• REPAIR THE DAMAGE – ANTIOXIDANT WHICH PENETRATE INTO THE SKIN

• FORMULATING CREAM FOR EFFICACY• FLOW THROUGH DIFFUSION TEST• RESULTS AND DISCUSSION• CONCLUSION

• Sunlight with UV spectrum can trigger the incidence of free radicals causing damage on human skin: photo aging

• It is important to repair the damage and neutralize the free radicals effect with antioxidant which can decrease the UV-radiation induced radical flux on the skin.

• Vitamin E known as an antioxidant can decrease the UV-radiation induced radical flux on skin, carried by the cream formulation containing emollients

• Emollients are occlusive carrier making the skin hydrated and then the skin cells become more swollen and enhancing the active ingredients to penetrate.

•The vitamin E as active ingredient should penetrate the stratum corneum which constitutes of dead cells, solid, and keratin cells and having very low diffusion coefficient.

•One of the efforts to enhance the penetration is to use the primary and secondary emollients (actually are lipid or oily materials) which are generally used to make the skin become soft and velvet.

• The primary emollient should have a relative polarity index identical or close to the active ingredient.

• Once it has been selected, a driving force for penetration into skin needs to be increased by reducing the solubility in the primary emollient.

• This is done by incorporating the secondary emollient in which the active ingredient is far less soluble but still miscible with the originally chosen emollient.

• When adding this secondary emollient, the solubility of the active ingredient is gradually reduced and the total amount of active ingredient dissolved relative to what could be dissolved, increases.

• Using vitamin E-acetate as active ingredient and selecting some emollients in the cream formulation, we try to obtain the best primary emollient to enhance the vitamin E-acetate skin penetration, tested by flow through-diffusion cell equipment.

THE EXPERIMENTTHE EXPERIMENT• The research was undergone in

Pharmaceutical Laboratory, Department of Pharmacy, Faculty of Mathematics and Sciences - University of Indonesia, and Pharmaceutical Technology Laboratory, Department of Pharmacy, Faculty of Mathematics and Sciences - Institute Technology of Bandung

MaterialMaterial• Vitamin E-acetate (Tocopheryl acetate - Cognis),

Castor oil, Olive oil, Peanut oil, tri-ethylhexanoate (Uniqema, Perdoni), steareth-21 (Cognis), steareth-2 (Cognis), squalane (Cognis), palmitic acid (Cognis), glycerin (Brataco), xanthan gum (Jungbunzlauer), methyl paraben and propyl paraben (Ueno Fine Chemicals Industry, Ltd), Whatman paper no.1, citric acid, cocos oil, methanol, cholesterol, sesame oil, oleic acid, stearic acid, white petrolatum, liquid paraffin (Pharmaceutical Laboratory of Department of Pharmacy, University of Indonesia).

EquipmentsEquipments

• Flow through-diffusion cell, penetrometer (HERZ009), pH meter (Istek), Spectro-photometer UV-VIS (Beckman 7500i), analytical balance (AG904), optical microscope (Nicon model Eclipse E200), digital camera (Nicon Coolpic 4500), water-bath, thermometer, glass-wares.

METHODMETHOD

• Selecting the emollients• Preparing the cream• Measuring the vitamin E-acetate

(tocopheryl acetate) diffusion

SELECTING THE EMOLLIENTSSELECTING THE EMOLLIENTS((the polarity index of the active ingredientthe polarity index of the active ingredient : :

VITAMIN E-ACETATE is 13.58)VITAMIN E-ACETATE is 13.58)

Primary emollients :• Castor Oil (Polarity Index 13.7)• Olive oil ( Polarity Index 16.9)• Peanut Oil (Polarity Index 20.5)Secondary emollient :• Tri-ethylhexanoate (Polarity Index 2.7)

• Preparation the cream

tocopheryl acetate, castor/olive/peanut oil, tri-ethylhexanoate, and propyl paraben was warmed at 70oC

steareth-21, steareth-2, glycerin, and citric acid was warmed while stirred at 70oC

Methyl paraben was dissolved in warm water

strongly mixed in warm vessel until emulsion was formed Xanthan gum

developed in water and strongly stirred

was added into the mixture and mixed to be completely homogenized

Measuring tocopheryl acetate Measuring tocopheryl acetate diffusiondiffusion

• Cream as much as 1 gram was placed on the plate of the diffusion cell and the instrument was set to operate, using Whatman paper impregnated by Spangler solution as the membrane. The receptor fluid was 50 ml and the sample was withdrawn as much as 1 ml after 10, 20, 30, 45, 60, 75, 90, 105, 120 and 180 minutes, then one ml of the receptor fluid was added to the sink to replace the solution. Into these samples 9 ml methanol was added before being measured by UV-VIS spectrophotometry.

Figure 1. The component part of Figure 1. The component part of the diffusion cellthe diffusion cell

Figure 2. Figure 2. Flow through diffusion cell,Flow through diffusion cell, front and side front and side viewview

EQUATIONSEQUATIONS

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formscp

p

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form

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RESULTS RESULTS The polarity index of• Vitamin E-acetate = 13.58• Castor Oil = 13.7• Olive oil = 16.9• Peanut Oil = 20.5• Tri-ethylhexanoate = 2.7

Results of cream evaluationThe cream has a good performance, white color with shining, specific odor, and good homogenity.

Results of tocopheryl acetate diffusion• The calibration curve is a linier regression with equation of: y = 0.038684 +

0.00585476 x and a regression coefficient of r = 0.99954• The Spangler solution absorbed on to Whatman paper is 101,53 ± 4,77• The results of tocopheryl acetate diffusion from cream X with Castor oil (polarity index

13.7) as the primary emollient was 4807.12 ± 7.90 µg/cm2, cream Y with Olive oil (polarity index 16.9) as the primary emollient was 362.61 ± 1.50 µg/cm2 , and cream Z with Peanut oil (polarity index 20.5) as the primary emollient was 198.04 ± 0.89 µg/cm2 within the test period of 180 minutes.

DISCUSSIONDISCUSSION

• The primary emollient (Castor oil) having polarity index very close to the polarity index of active ingredient (Vitamin E-acetate) gave better penetration because they contain the component of fatty acid ricinoleat as much as 87%.

CONCLUSIONCONCLUSION• It was concluded that cream X containing

castor oil as the primary emollient having the polarity index closest to the polarity index of the active ingredient was capable to enhance tocopheryl acetate penetration compared to cream Y and Z with less close polarity index to the active ingredient. The secondary emollient was same for all the three cream formulations.