INTRODUCTION:

Indonesia is a country rich in biodiversity resources and has the highest marine species. About 45% of the world's seaweed species exist in Indonesia. Reported from Siboga expedition, in Indonesia there are about 782 species of seaweed with 196 species of green algae, 134 species of brown algae, and 452 red algae¹.

Red algae (Eucheuma sp.) is one of the marine biota that the people of Indonesia widely use, especially the people in West Nusa Tenggara (NTB). NTB can produce red algae up to 387 tons per year, but in fact, just a few among has been taking advantage, one example is to make it for food material².

Whereas more than that, the development of red algae is an opportunity for the food, cosmetics, pharmaceuticals, and community industries to increase their use value by using red algae. Particularly, red algae can be extracted and produced in many product cosmetics and skin care which can be prepared that are very convenient and easy to use, one of the preparation is gel form². The gel form is well to apply topically and it can increase and accelerate the desired therapeutic effect. In addition, the gel form is able to stay longer on the surface of the skin and retain the moisture of the skin so can avoid irritation³. Most of the commercial skin whitening products currently contain kojic acid, arbutin, catechin, hydroquinone (HQ) and azelaic acid as one of the important ingredients⁴. The detrimental effects of these synthetic compounds are irreversible⁵. Therefore paving the way for the search for skin lightening active ingredients that are safer from plants with strong antioxidant properties⁶.

The skin is the outermost organ that covers the surface of the body and is most often exposed to the sun. Indonesia is a tropical country with abundant sun exposure, therefore it is a high risk of skin damage. Exposure to UV light causes the formation of free radicals from ROS (reactive oxygen species) which are unstable molecules. In addition to exposure to sunlight, free radicals are also obtained from activities of daily life such as cigarette smoke, fried and baked foods, fumes, certain drugs, toxins, and air pollution. Free radicals are unstable and in an effort to make up the number of electrons and will bind to cell components to become stable so that they will damage cell components such as fats, proteins, and nucleic acids. Damage to cell components will cause premature aging of the skin which is characterized by dryness, wrinkles, and dullness. To prevent this, we need a skincare antioxidant substance such as gel preparation that delays, controls, or inhibits the cell's oxidation process that can prevent premature aging⁷.

Reported research by Mardiyah (2014)⁸ that the EC₅₀ value for Eucheuma spinosum extract with the methanol fraction was 22.13. The IC₅₀ value with 95% methanol solvent in the research of Allindra Poudungge et al. (2018)⁹ is 97.522 ppm. In a study also conducted by Oktarina (2017)¹⁰ it was stated that the flavonoids present in red algae have great effectiveness in skincare, especially whitening¹¹. Flavonoids are known to reduce lipid peroxidation and prevent cell damage¹¹. Currently, there is no scientific research on red algae (Eucheuma spinosum) from Lombok island which is formulated in antioxidant gel form. So that the researchers were interested in examining the physical stability and antioxidant activity of the red algae gel form.

MATERIALS AND METHODS:

Materials:

Red algae (Eucheuma spinosum) was obtained from Gili Tangkong, Sekotong, West Lombok. Other materials used were 1,1-diphenyl-2-picrylhydrazyl (DPPH) (SigmaChem.co, Germany), ethanol 96%, carbopol 940, HPMC (Merck), methylparaben (Merck), propylene glycol, NaOH (Merck), rose water (Biomed) 96% ethanol and distilled water (BrataChem, Indonesia).

Preparation of Extract:

The collected red algae were washed thoroughly in salt water several time, then finally rinsed with distilled water in room temperature. Dried samples were pulverized with blender¹². The powder sample 500g of red algae extracted with 96% ethanol by maceration method at room temperature for 24 h. The macerate was suspended in a mixture ratio of the solvent used is (1:12) with the remaceration method 3x24 h¹³. Then, the maserate was evaporated using vacuum rotary evaporator (B-One) and continued in a porcelain dish over a water bath (Memmert GmbH.co, Germany) until the thick mass was obtained.

Preparation of Red Algae Extract Gel (Eucheuma spinosum):

The design of the red algae extract gel formula refers to the formula produced by Suryani (2017)¹⁴ which can be seen in Table 1 using three variations of Eucheuma spinosum extract concentration. Extract samples were added with 10%, 20%, 30%, and control gel without the addition of extract which were indicated as F1, F2, F3, and F0 respectively.

Carbopol was dissolved in distilled water that has been heated (temperature 70-80°C) then stirred using an electric stirrer. After the foam disappeared, 0.4g of NaOH solution was added to dissolved carbopol 940 to neutralized the carbopol 940 until prepared homogenous dispersion and swelled gel mass was formed. Then, methyl paraben was dissolved in propylene glycol, then added to the gel base¹⁵. The red algae extract that had been made with various concentrations was put into the gel base as much as the weight of the extract according to the formula, then stirred until homogeneous using a stirring rod. The finished gel is then filled into a tightly closed container for further gel evaluation.

Evaluation of Stability Gel Preparation:

The stability test carried out on this red algae extract gel using an accelerated stability test in room temperature around 27-30⁰C for 21 days. Observations started from days 0, 3, 7, 11, 15, 18, and 21 days of storage¹⁶.

a) Organoleptic:

Observations were seen directly visually from the shape, color, and smell of the gel preparations made. Performed on day 0, 3, 7, 11, 15, 18, and day 21 at room temperature¹⁷.

b) pH Test:

the test was carried out by using digital pH meter. A total of 5g of gel was dissolved with distilled water to 50 mL. The electrodes on the pH meter were washed first with distilled water, then calibrated in standard solutions of pH 4 and pH 7. The calibrated electrode was immersed in the sample and the number indicated on the pH meter was known¹⁸.

c) Spreadability test:

The test is carried out by placing of 1g of the gel preparation on a glass slide and then covered with another glass slide and the diameter was measured from five corner points. Then the top gel layer is given of various weight, allowed to stand for 1 - 2minute interval and the diameter of the spread was recorded when the preparation stops spreading. The dispersion diameter is measured at each additional load, then when preparation stop spreading within a certain time regularly. A good spreadability area ranges is 5-7cm¹⁹.

d) Adhesion Test:

The adhesion test was carried out by placing the gel on two slides as much as 0.25g, then pressed with a load of 1kg for 5 minutes. After that, the slide is mounted on the test instrument and then a load of 80g is added to the test instrument, then the time of release from the slide is recorded²⁰.

e) Viscosity test:

Viscosity testing is carried out using Brookfield Viscometer LVT type with spindle number 4. The method of measurement is that 100mL of gel is inserted into a beaker, then the spindle is installed and inserted to a predetermined limit. The viscometer is turned on and rotated at 6rpm until the viscometer needle shows a constant number²¹.

Antioxidant Activity Test of Red Algae Extract Gel:

Preparation of DPPH Solution:

One hundred part per million of DPPH was dissolved in 70% ethanol as stock solution. Then the solution was mixed thoroughly, stored it in a dark and measured at a maximum wavelength of 400-700nm²¹.

Preparation of 100ppm Quercetin Solution:

One hundred part per million of quercetin as comparison was dissolved in methanol and mixed thoroughly. Then the solution was pipetted at 3 concentrations. Then 1ml of DPPH solution was added in the various concentrations individually and the volume was made up with ethanol up to 5ml to obtain quercetin concentrations of 10ppm, 20ppm, and 30ppm. After incubation for 30minutes at room temperature in the dark, the decrease in absorbance of DPPH radical was measured at a wavelength of 515nm²².

Antioxidant activity testing:

Weigh the 100mg preparation of each concentration (10%, 20% and 30%) and extract, dissolve with 100ml of 70% ethanol until homogeneous, so that a solution with a concentration of 1000ppm is obtained. From the stock solution, each 0.5ml, 1ml, 2ml pipette was pipetted, then 1ml of DPPH solution was added and the volume was filled with ethanol up to 5ml to obtain concentrations of 100ppm, 200ppm, and 400ppm. The mixture was shaken and allowed to stand for 30minutes at room temperature. The absorbance of each solution was measured at a wavelength of 515nm, 3 replications were carried out²³. After which a standard curve was made between concentration (ppm) and %inhibition.

Blanko Absorbance – Sample Absorbance

% Inhibition = ------------------------------------- ×100%

Blanko Absorbance

Blank Absorbance:

Absorbance Value DPPH;

Sample Absorbance:

Absorbance Value of the added DPPH solution.

Furthermore, IC₅₀ was determined using the concentration as X and % inhibition as Y, so a and b values were obtained in the regression equation Y = aX + b. Then the Y value was substituted with 50 in the equation, and the X value was obtained as the IC₅₀ value.

RESULT:

Evaluation of the physical stability of the gel:

The stability test was performed to understand the ability of product to maintain the same condition in physiochemical and stability of the sample. According to the result of organoleptic test (table 2), all formulas showed no experience of changing either before or after stored.

Table 2: Evaluation organoleptic test result of Extract red algae gel

Formula	Organoleptic
Formula	Day 0	Day 3	Day 7	Day 11	Day 15	Day 18	Day 21
F0 (0% Gel extract red alga)	Clear, Semisolid, rose waters	No changes	No changes	No changes	No changes	No changes	No changes
F1 (10% Extract )	Bright yellow, Semisolid, the smell of algae	No changes	No changes	No changes	No changes	No changes	No changes
F2 (20% Extract )	Gold Yellow, Semisolid, the smell of algae	No changes	No changes	No changes	No changes	No changes	No changes
F3 (30% Extract )	Light brown, Semisolid, the smell of algae	No changes	No changes	No changes	No changes	No changes	No changes

Table 3. Physical stability result of extract red algae gel

Time (Day)	PH*
	Base (0% Gel extract red alga)		F1 (10% Gel exstract)		F2 (20% Gel extract)		F3 (30% Gel extract)
0	5.03 ± 0.06		4.50 ± 0.00		4.97 ± 0.06		5.43 ± 0.12
3	7.30 ± 0.00		7.43 ± 0.06		7.63 ± 0.06		7.80 ± 0.00
7	7.63 ± 0.06		7.16 ± 0.00		7.13 ± 0.01		7.14 ± 0.00
11	7.20 ± 0.00		7.32 ± 0.01		7.45 ± 0.01		7.67 ± 0.06
15	7.86 ± 0.01		7.97 ± 0.01		7.97 ± 0.01		7.93 ± 0.00
18	7.92 ±0.01		8.15 ± 0.01		8.17 ± 0.00		8.33 ± 0.00
21	7.23 ± 0.00		7.12 ± 0.01		7.15 ± 0.00		7.23 ± 0.00
Time (Day)	Spreadability (cm)*
	Base (0% Gel extract red alga)		F1 (10% Gel extract)		F2 (20% Gel extract)		F3 (30% Gel extract)
0	4.53 ± 0.06		4.37 ± 0.06		4.57 ± 0.06		4.17 ± 0.06
3	4.93 ± 0.06		4.67 ± 0.06		4.73 ± 0.06		4.50 ± 0.00
7	6.87 ± 0.06		5.40 ± 0.10		5.33 ± 0.06		5.57 ± 0.06
11	7.23 ± 0.15		6.37 ± 0.12		6.63 ± 0.06		6.27 ± 0.06
15	6.80 ± 0.10		5.23 ± 0.06		6.63 ± 0.15		5.40 ± 0.00
18	6.27 ± 0.06		5.27 ± 0.12		6.17 ± 0.06		5.33 ± 0.06
21	6.57 ± 0.06		5.97 ± 0.06		5.47 ± 0.06		5.10 ± 0.00
Time (Day)	Adhesion (Second)*
	Base (0% Gel extract red alga)		F1 (10% Gel extract)		F2 (20% Gel extract)		F3 (30% Gel extract)
0	3.16 ± 0.01		3.23 ± 0.06		3.15 ± 0.00		5.55 ± 0.01
3	3.17 ± 0.01		3.25 ± 0.01		3.36 ± 0.01		5.58 ± 0.00
7	3.54 ± 0.01		4.01 ± 0.01		3.45 ± 0.01		5.65 ± 0.01
11	4.09 ± 0.01		4.09 ± 0.01		4.00 ± 0.00		4.65 ± 0.01
15	3.16 ± 0.01		3.18 ± 0.01		3.38 ± 0.01		4.58 ± 0.00
18	3.10 ± 0.00		3.15 ± 0.01		3.24 ± 0.00		4.51 ± 0.01
21	3.33 ± 0.58		3.01 ± 0.00		3.18 ± 0.00		4.47 ± 0.01
Time (Day)	Viscosity (cps)*
	Base (0% Gel extract red alga)	F1 (10% Gel extract)		F2 (20% Gel extract)		F3 (30% Gel extract)
0	1802 ± 0.58	3468 ± 0.58		3763 ± 0.58		3356 ± 0.58
3	1846 ± 0.58	3500 ± 0.58		3840 ± 0.58		7371 ± 1.00
7	1846 ± 0.58	3500 ± 0.58		3847 ± 0.58		7951 ± 1.53
11	1848 ± 0.58	3536 ± 0.58		3855 ± 0.58		8431 ± 1.15
15	1861 ± 1.15	3392 ± 1.15		3984 ± 0.58		9009 ± 1.53
18	1854 ± 0.58	3356 ± 0.58		3998 ± 0.58		9172 ± 2.00
21	1852 ± 0.58	3337 ± 0.58		3956 ± 0.58		16651 ± 2.08

Table 2 showed that the three red algae extract gels F1 (10%) and, F2(20%), and F3(30%) showed a distinctive aroma of red algae, from the three formulas it looked clear and there was a slight difference in color intensity (yellowish brown which was different) in each formula except control (F0). The more concentrated the extract in the cream preparation, the higher the color intensity, but no significant difference. Gel with intense color intensity is an extract gel with a concentration of 30% (F3). The results of pH stability test (Table 3) and figure 1 showed that all formulas red algae extract gels stable in the day 3 to 21. The diameter of the dispersion test which is comfortable to use for semi-solid is 4-7 cm or dispersion area ranges from 19.63-38.46 cm², which mean all formulas demonstrated in good spreadable until the day 21. Susceptible in good adhesion test on the preparation of semi-solid is 1 - 10 seconds. The results of measurements and observations of the viscosity value of the red algae extract gel (Table 3) for 21 days showed that the basic formula, F1 (10%), and F3 (20%) were stable, while F3 (30%) was unstable because the viscosity on day 3 to day 21 did not show as a good viscosity as the standard ranges from 1000 – 4000 cps²⁴.

Figure 1: Observation Chart of (1) pH (2) Spreadability (3) Adhesion and (4) Viscosity

Antioxidant activity of gel:

The antioxidant activity test of the red algae extract gel was carried out using the DPPH method with 70% ethanol as a solvent in UV-Vis spectrophotometer analysis. The antioxidant activity test was repeated 3 times, namely 100ppm, 200ppm, and 400ppm. The maximum wavelength of DPPH is measured at a wavelength of 400-700nm²². Thus, measurements of antioxidant activity were carried out at a maximum wavelength of 515nm in all samples.

The correlation between concentration and % inhibition indicated the antioxidant activity. (Figure 2) shows the results of the % inhibition measurement, and the IC₅₀ value of the test solution can be seen in (Table 4) shows the IC₅₀ value of Quarcetin is 7.12ppm, and the IC₅₀ value of control red algae extract is 81.48ppm and 1069.69ppm, respectively. While the three gel extract formulas F1, F2, and F3 IC₅₀ values are 198.88ppm, 153.85ppm, and 101.18ppm which indicate that the concentration of a red algae gel sample is a sample concentration that is able to reduce DPPH activity by 50% (purple, blue and orange lines). The IC₅₀ value of red algae extract was stronger than all formula groups and weaker than Quarcetin. One-way ANOVA statistical analysis showed that there was no significant difference between the three formulas (p>0.05), and the IC₅₀ values of the three formulas were significantly different (p< 0.05) with base gel extract of red algae and not significantly different (p>0.05) with preparation of red algae extract.

Table 4: Results of the inhibitory concentration IC₅₀

Sample	IC₅₀ (ppm)
Comparison: Quersetin	7.12^a
Extract	81.48^a
F0 (Gel form only)	1069.69^ab
F1 (10% Gel extract)	198.88^b
F2 (20% Gel extract)	153.85^b
F3 (30% Gel extract)	101.18^b

(^a.b) if the same latters are significantly different p< 0.05

Figure 2: The correlation of inhibition (%) and concentration (ppm) of sample

DISCUSSION:

Gel can be clearly forming gel formula when all of the particles completely dissolved in the gel basics²⁵. In this study, the gel forming with carbopol polymer and HPMC. Carbopol are very good water absorption and able to swell 10 times their original diameter to form gel when in pH environment above 4.0 to 6.0²⁶. The combination of hydrogel polymers can lead the swell and retain large amount of water²⁷. The formula standard in this study was carried out based on the Suryani optimation formula (2017)¹⁴. Gel preparations from red algae extract and physical stability and antioxidant activity test were determined. Organoleptic examination was carried out by direct observation without using tools for 21 days by applying a gel on the skin of the arm (table 3). The all red algae gel formulas showed the clear preparation with a distinctive aroma of algae extract and showed the intensity of the yellow color for 21 days of observation from different extract gel concentrations. The higher the concentration, the more intense the color, although there is a slight difference in concentration²⁸. The pH range of semi-solid preparations that are good for skin is in the pH range of 4.5-6.5²⁹. Based on the results of the pH test (Table 3), the pH of 3 formulas during the storage period, formulated gel exhibited only minor changes after the 3rd day to the 21st day. This is presumably due to the effect of changes in storage temperature on propylene glycol so that it increases the pH value of all gel preparations. Changes in the pH value of the preparation are influenced by propylene glycol which is decomposed by changes in temperature during storage and testing. Propylene glycol has stability at 25⁰C. At temperatures above 25⁰C, propylene glycol will be easily decomposed and oxidized which causes an increase in pH³⁰.

The results of the dispersion test of the three formulas on the observation day 0 to day 21 (Table 3) have a diameter value of the dispersion test that is comfortable in use for semi-solid preparations, namely 4 - 7cm or in other words, the spreadability ranges from 19, 63-38.46 cm²^,³¹. The dispersion test value during observation decreased and increased. According to Aryani (2015) the viscosity of a preparation is very influential on the extent of its distribution, the higher the viscosity of a preparation, the smaller the dispersion will be. The higher the concentration of the added extract, the higher the consistency and the lower the spreadability of the cream preparation³². Adhesiveness of the preparation describes the ability to adhere to the skin, high adhesion indicates the preparation is not easily lost. The average adhesion test value of all extract gel formulas for 21 days was unstable, but if viewed from the value of the adhesion test each formula met the requirements for semisolid preparations. preferably the adhesion of semisolid preparations is more than 1 second³³. Adhesion is affected by the viscosity of the base. Adhesion is closely related to viscosity. The higher viscosity is caused by the higher consistency of the preparation so that the adhesion time becomes longer³⁴. Viscosity is an expression of a liquid's resistance to flow. The higher the flow viscosity, the greater the resistance. Gel preparations were measured viscosity on days 0-21 days of storage at room temperature (27-300 ⁰C)³⁵. This observation uses spindle No. 3 at rpm 6, a good viscosity range from 1000 - 4000cps³⁶. The value of gel viscosity (Table 3) observed on the 3rd day to the 21st day at F3(30%) increased, while on a gel basis, F1 (10%), and F2(20%) were still in a good viscosity range. If we look at the viscosity value in (Table 3) shows the viscosity value in the base formula, F1(10%), F2(20%), and F3(30%) increased with storage time. One of the polymers contained in red algae is carrageenan³⁵. Carrageenan has water binding properties so that it can affect the increase in the viscosity of a preparation³⁷. In the other case, additing HPMC in the gel component also lead the increasing viscosity of the formulation and exhibited pseudo plastic type³⁸. The result of this study is in line with research of Slamet (2020)³⁹ on the stability test of Moringa leaf extract gel which states that the higher the viscosity value along with the length of time the preparation is stored.

The IC₅₀ value of the quercetin solution was at a very strong intensity (<50ppm) at 7.12ppm (Table 4). In previous studies, the IC₅₀ value obtained in the antioxidant testing of the kesumba rivet seed methanol extract conducted by Fensia Analda Souhoka was included in the very strong intensity at 8,485 ppm³⁸. Quercetin was used as a comparison because quercetin is a flavonoid of the flavonol group which has a keto group at C-4 and has a hydroxy group on the C-3 or C-5 atom so that it can form a color complex with AlCl₃⁴⁰. The IC₅₀ test results of red algae extract in this study 81.48 ppm showed weaker antioxidant activity than quarcetin IC₅₀. Quercetin as a positive control is a single compound, which means that the IC₅₀ value obtained by quercetin is a value that actually comes from the compound, while the red algae extract represents several secondary metabolites that have not been separated⁴¹. The highest IC₅₀ value of the three formulas was found at F3 (30%) 101.18 ppm which included the category of moderate intensity antioxidant (101ppm < IC₅₀ <150 ppm), while formulas F1(10%) and F2(20%) belonged to the category of antioxidant intensity. weak (151<IC₅₀<200ppm). The results of this study are in line with research conducted by Abdul (2022) on testing the antioxidant activity of the cream of ethanol extract of gaharu leaves (Aquilaria malaccensis L.) with the highest antioxidant activity value in the third formula of 5%. Statistical analysis showed no significant difference (p>0.05) between the quarcetin group, the extract group and the formula group. These results indicate that the ability of formulas F1(10%), F2(20%), and F3(30%) as antioxidant activity is the same as the quarcetin and extract groups, but the IC₅₀ of the three formulas shows that the strength of antioxidant activity at F1 (198.88 ppm) and F2(153.85) in the weak category, and F3 (101.18 ppm) in the medium category (Table 4). While statistical analysis data between the quarcetin group and the extract group showed that there was a significant difference (p<0.05) meaning that the antioxidant activity of quarcetin was stronger than the extract group, this might be because the ethanolic extract of red algae was still a crude extract when compared to quercetin. pure compound so that the active compound content is very small⁴². The quercetin compound isolated from the methanol extract of the leaves and flowers of Quiaqualis indica It is carried out by various physical techniques (solvent extraction and chromatography) which has been shown to have antioxidant activity⁴³. The antioxidant activity of a compound was categorized as very strong (IC₅₀ <50), strong (IC₅₀ = 50-100), moderate (IC₅₀ = 100-150), and weak (IC₅₀ = 151-200). The smaller the IC₅₀ value, the higher the antioxidant activity⁴⁴. These data indicate that the higher the concentration of the extract, the more active its free radical scavenging power¹⁵. The three gel formulas showed moderate and weak antioxidant activity, which means the presence of flavonoid compounds in the red algae extract gel formula was suspected. Compounds that usually have antioxidant activity are phenolic compounds with hydroxyl groups (–OH) and alkoxy groups (–OR)⁴⁵. According to Jenifer et al., (2017)¹² research, marine algae produce various kinds of active chemical metabolites in their surroundings, these active metabolites are also known as biogenic compounds such as halogenated compounds, alcohols, aldehydes, terpenoids produced by several marine algae species and have antioxidant

CONCLUSION:

Red algae extract gel (Eucheuma spinosum) produced physical stability during 21 days of observation, showing it was stable on organoleptic, spreadability, and adhesion tests, while pH and viscosity tests showed unstable. The IC₅₀ values of red algae extract gel at concentrations of 10%w/w, 20%w/w, and 30w/w, respectively, were 198.88, 153.85, and 101.18 ppm, indicating that the ability of the antioxidant activity of F1 (10%w/w) and F2(20%w/w) weak category, and F3 (30%w/w) moderate category.

CONFLICT OF INTEREST:

The author(s) declare(s) that there are no conflicts of interest regarding the publication of this article.

ACKNOWLEDGMENTS:

The researcher would like to thank the Pharmacy study program, Faculty of Health Sciences, University of Muhammadiyah Mataram for the support and laboratory facilities provided to us in 2022.

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Received on 12.09.2022 Modified on 16.05.2023

Research J. Pharm. and Tech 2023; 16(10):4729-4736.

DOI: 10.52711/0974-360X.2023.00768

S. No.	Materials (% w/w)	Function	Formulation
S. No.	Materials (% w/w)	Function	F1	F2	F3
1	Red algae extract	Active substance	10	20	30
2	Carbopol 940	Gelling agent	1.5	1.5	1.5
3	HPMC	Gelling agent	0.5	0.5	0.5
4	NaOH	Buffering agent	0.4	0.4	0.4
5	Propilen glikol	Humectant	10	10	10
6	Metilparaben	Preservative	0.09	0.09	0.09
7	Rose water (drops)	Soothing agent	7	7	7
8	Distilled water ad	Carrier	100	100	100