Meiti Rosmiati*, Marline Abdassah, and Anis Yohana Chaerunisaa
Dept. of Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University Korespondensi : firstname.lastname@example.org (Meiti Rosmiati)
Keywords : Tocopherol acetate, Vitamin E, emulgels, carrageenan
Vitamin E is a lipid soluble antioxidant that is essential for the maintenance of healthy skin. Naturally occurring vitamin E is not a single compound; instead, vitamin E is a group of molecules with related structures, some of which may have unique properties in skin. Vitamin E is normally provided to the skin through the sebum. Topical application can also supply the skin with vitamin E and may provide specific vitamin E forms that are not available form the diet1.
When gel and emulsion are used in combined form the dosage forms are referred as emulgel2. As the name suggest they are the combination of emulsion and gel. In recent years, there has been great interest in the use of polymers with complex functions as emul- sifiers and thickeners3.
One of a carbohydrate polymers is Carrageenan that derived from seaweed particularly Eucheuma cottonii4, caraageenan has the ability to form gels in a thermoreversible waymaking it widely used as a gelling agent, thickener, and stabilizer in various industries such as food, pharmaceuticals, cosmetics, printing, and textile5. Application and use of carrageenan in the manufacture of gels and other gel products is still very limited especially for cosmeceutical products. Therefore, it is necessary to conduct a study on the effect of the concentration of gelling agent as to provide more comprehensive data related to the physical properties of the gel produced. For this purpose carrageenan was chosen, a polysaccharide and has very interesting properties like good adhesiveness on skin which can be a benefit for topical application6.
In this research, the aim study is to formulate Tocopherol acetate (Vitamin E) in emulgels, using Carrageenan as gelling agent as well as to evaluate its characteristics.
Materials and Methods
Carrageenan was obtained as a gift sample from Padjadjaran University (Bandung,Indonesia). Tocopherol Acetate (Vitamin E) (Brataco Chemical), Span 20 (Brataco Chemical), Tween 20 (Brataco Chemical), Parrafin liquidum (Brataco Chemical), Propylene glycol (Brataco Chemical), Methyl and Propyl Paraben (Brataco Chemical), Triethanol Amine (Brataco Chemical). All other chemicals used were of analytical grade.
2.2. Emulgel Basis
Orientation Basis selection was done by using varying amount of Carrageenan as gelling agent as much as 0.5% (F1), 0.75% (F2), 0.85% (F3), 0.95 % (F4), 1% (F5), 1.125% (F6), 1.25% (F7), 1.5% (F8) and 2% (F9). The composition of different formulations of emulgels is shown in Table 1.
2.3. Preparation of Tocopherol Acetate (Vitamin E) Emulgel
Different formulations were prepared using varying concentration of carrageenan as a gelling agent for tocopherol acetate emulgel. The preparation of emulsion was same in all the formulations. The gel bases were prepared by dispersing Carrageenan in heated distilled water (75OC) with constant stirring at a moderate speed using mechanical shaker and adjusted to 5.5 to 6.5 using tri ethanol amine (TEA). The oil phase was prepared by dissolving certain amount of span 20 in liquid paraffin, while the aqueous phase was pre- pared by dissolving the required amount of tween 20 in purified water. 0.03 g of methyl paraben and 0.01 g propyl paraben were dissolved in 10 g of propylene glycol and both were mixed with aqueous phase. Tocopherol Acetate was dissolved in oil phase. Both the oily and aqueous phases were separately heated to 70-80°C. Then, the oil phase was added to the aqueous phase with continuous stirring until it got cooled to room tempera- ture. The emulsion was poured into a gel with gentle stirring until homogenous emulgel was obtained7,8,10.
The antimicrobial activity of methyl paraben and others is considerably reduced in the presence of nonionic surfactants, as a result of micellization. However, propylene glycol (10%) has been shown to potentiate the antimicrobial activity in the presence of nonionic surfactants9.
2.4. Evaluation of emulgel
2.4.1.Physical parameters of prepared formulations
All the prepared formulations were visually checked for the color, appearance, homogenicity, phase separation and freeze thaw test.
2.4.2.Determination of pH
The pH measurements were done using a digital pH meter (Mettler Toledo). Gel (1 g) was dissolved in 25 ml of distilled water and the electrode was then dipped in to gel formulation until the constant reading was observed. The measurement determination of pH of each formulation were measured in three replicate7.
2.4.3.Determination of viscosity
The viscosity of each formulations was determined at ambient temperature using Brookfield digital viscometer with spindle no.5 at 50 rpm8.
3.1. Emulgel Base Orientation Result
Based on the result in Table 3 and Ta- ble 4. Formulas F5, F6 and F7 show the beter results in consistency, phase separation, and freeze thaw test compare to formulas F1, F2, F3, F4, F8 and F9, only formulas F5, F6 and F7 have condition easy to spread and no phase separation after freeze thaw test, meanwhile F8 and F9 have no phase separation but their consistency harder and very stiff.
3.2. Formulation Tocopherol Acetate (Vitamin E) Emulgels
The freeze thaw test show that the F5, F6 and F7 have good stability in the concentration of Tocopherol Acetate was 5%12. The whole Formulation can be seen in Table 5.
3.3. Physical Stability Study of Tocopherol Acetate (Vitamin E) Emulgels
Table 6 and figure 1 show the physi- cal properties of the emulgels in F5, F6, and F7. The result shows that F5 has the better formula based on parameters such as pH measurement and spreadability test. The F5 continues to stability test and figure 2 indicat- ing stability studies data of F5 formula. 4.
Nine formulations of emulgel with carrageenan as gelling agent were prepared as indicated in Table 1. From preliminary trials it was found that when carrageenan was used beyond 1.25% the gel base obtained was highly viscous making it unfavorable to used. Similarly at concentrations below 1% the vis- cosity was very poor. Hence carrageenan was used in the range of 1-1.25% in formulations F5-F7.
The result of various physical param- eters evaluated are given in Table 3,4. Formu- lations F1-F4 were fluid due to the presence of low carrageenan concentrations. Formula- tions F8-F9 were thick due to higher carrageenan concentrations. Formulations F5-F7 have creamy appearance and no phase separation was observed at centrifugation test ant freeze thaw test.
Based on viscosity, spreadability and pH measurement result of formulas F5-F7, formula F5 was found to be the best for formulating tocopherol acetate emulgel from parameters pH measurement F5 that has pH values between 6-6.5, meanwhile F6 and F7 have pH values above 6.8, that slightly beyond safe level for skin topical requirements which was at the range 4.5-6.813. For spreadability test F5 belonged to fluid gel category, and formulations F6 and F7 with higher concentration of carrageenan belonged to semi fluid gel and semi stiff gel to stiff gel respectively. With an increase in gelling agent concentration in formulation, the spreadability of formulations decreases8. The result are reported at figure 1.
Accelerated stability studies were per- formed for formulation F5 for 3 months. The samples were analyzed for 0,7,14,28.45.60 and 90 days for physical appearance, viscos- ity, pH and spreadability.
4.1. Result of physical appearance determination
The result of organoleptic observation shows in Table 6, that during strorage time emulgel does not shows any changes in odor and color.
4.2. Result of viscosity determination
The result of viscosity measurement during storage time was shown on Figure 2. The viscosity value at room temperature stor- age is more stable than that stored at high temperature at climatic chamber and at cold temperature. This corresponds to the Arrhenius kinetics equation where the viscosity is inversely proportional to the temperature. The higher the temperature the lower the viscosity value. In addition to temperature, storage time affects stability of dosage form. The longer the preparation is stored at climatic chamber then the viscosity value will be lower because of the influence of the high humidity so that the preparation to absorb water vapor and cause increased volume of preparations.
4.3. Result of pH measurement
The pH of emulgel preparation that has been made were still on safe level for skin topical requirements which was at the range 4.5-6.813. The measured values are present- ed in figure 2 that indicated the suitable of emulgel for topical application.
4.4. Result of spreadability measurement
The result of spreadability measurement during storage time was shown on figure 2. Spreadability it is observed that by increasing viscosity spreadability is decreased. The spreadability value at room temperature storage is more stable than that stored at high temperature at climatic chamber and at cold temperature. The data are given as the mean and standard deviation of each parameter at each temperature and after each storage period. All results were compared by analysis of variance (ANOVA) for a 95% confidence level to identity significant difference.
This research shows that emulgels based on carrageenan as the gelling agent with of active ingredient Tocopherol acetate. Form this research we can also know that promising formula F5 emulgel preparation that are consist of concentration carrageenan 1%, tocopherol acetate 5%, tween 20 and span 20 (1 and 1.5 %), liquid paraffin 7.5%, propylene glycol 10%, propyl and methyl paraben (0.01% and 0.03%), tri ethanol ami- en 2% has better pharmaceutical requirement from the others formulas and stable during strorage at ambient temperature, at climatic chamber and at cold temperature without any signifycant stability problems.
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