Formulation of Gel Preparations of Ethanol Extract of Indian Strawberry (Duchesnea indica (Jacks.) Focke.)

 

A. Mumtihanah Mursyid*, Risda Waris, Wahida W. Ilham, Asni Amin

Pharmaceutical Department, Faculty of Pharmacy, Universitas Muslim Indonesia.

 

ABSTRACT:

The anti-inflammatory activity of Indian strawberry leaves is 0.31 percent DAI. For the treatment of inflammation, gel formulations are selected as effective penetration agents. The purpose of this work was to manufacture and test a pharmaceutically stable gel formulation of ethanol extract of Indian strawberry (Duchesnea indica (Jacks.) Focke] leaf with anti-inflammatory properties. This experimental study approach involved developing four formulas: F1 with 3% NaCMC, F2 with 4% NaCMC, F3 with 8% HPMC, and F4 with 9% HPMC. Then, the next test was evaluate the physical stability of the formulation using the following test parameters: organoleptic, pH, homogeneity, spreadability, and viscosity at 5°C and 35°C. The organoleptic test revealed that there was no difference between the four formulae in the color, odor, and consistency series. Each of the pH formulae that passed the pH test were suitable for topical application to the skin. For the homogeneity test all formulas are homogeneous. The best dispersion for the dispersion test was found in formulas 2, 3, and 4. Based on the rheogram, F1, F2, F3, and F4 had pseudoplastic flow characteristics. According to the results of the research conducted, the ethanol extract of Indian strawberry leaves can be formed into gel formulations based on HPMC and NaCMC. The gel formulation formula for ethanol extract of Indian strawberry leaves is pharmaceutically stable.

 

 

 

INTRODUCTION:

Inflammation is a normal, protective response of the body to tissue injury caused by physical trauma, chemicals, or microbiological agents. Inflammation is the body's attempt to inactivate and destroy invading organisms, remove irritants, and prepare stages for tissue repair²².

 

Inflammation can be relieved using synthetic anti-inflammatory drugs, one of which is the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are synthetic drugs with a heterogeneous chemical structure. However, the use of NSAIDs can cause side effects on the gastrointestinal tract³¹. Therefore, with the side effects of synthetic drugs that will harm humans, the use of plants as an alternative anti-inflammatory treatment in the modern era is very promising. Therapy using ingredients derived from plants, either in the form of parts or organs of plant extracts, active isolates of a plant is called phytotherapy, anti-inflammatory drugs themselves have shown promising clinical efficacy related to mild side effects³³.

Various studies regarding the use of plants as a treatment have been reported. One of the plants that can be used as a medicinal ingredient is Arbenan leaves [Duchesnea indica (Jacks.) Focke] which is known to have anti-inflammatory effects. Arbennan plants grow in many countries and are also found growing wild in the mountainous areas of Malino and Bawakareng, Gowa, South Sulawesi. People use it as a traditional medicine because it can reduce fever and is a stimulant. In addition, Arbenan leaves can reduce swelling and are used as an anti-inflammatory. Empirically this plant has been used as a traditional medicine for burns. The group of compounds contained in Arbennan plants are polyphenols, triterpenes, triterpene glycosides, glycosides, sterols, and flavonoids¹².

 

According to Kusumawardhani et al. (2015), steroids are anti-inflammatory as well as flavonoids which have pharmacological activity as anti-inflammatories and are antioxidants by reducing excessive ROS, antibacterial and can increase wound contraction with their antimicrobial and astringent properties¹⁴. One of the studies on the benefits of Arbenan leaves is the research of Mursyid and Waris (2021) on the ethanol extract of Arbenan leaves which has an anti-inflammatory effect on white rats using an experimental method based on inhibition of the induction of swelling of the edema on the soles of rats' feet with the results of research on the ethanol extract of Arbenan leaves having an anti-inflammatory effect. Based on data from the calculation of the percent DAI (Anti-inflammatory Power) of the Arbenan leaf extract group, which was 0.31%, the Arbenan leaf extract treatment group effectively inhibited inflammation¹⁸.

 

Inflammation can be treated with the topical administration of drugs. The advantages of topical administration of anti-inflammatory drugs are that they could be directly applied to the inflamed area thus enable immediate effect, they arereleased slowly so that the duration of the effect can be longer, and they couldreduce the frequency of usage, which in turn increases the level of patient’scompliance⁴⁰. Several previous studies have formulated anti-inflammatory preparations in the form of gel, cream, and ointment preparations^29,32. The topical prepared proves to be the better alternative for the oral administration of NSAID and eliminates the limitations of the drug-like gastric disturbances, low bioavailability; short half-life, and first-pass effect³⁶.

 

According to the Indonesian Pharmacopeia VI edition (2020), Gel, or sometimes is referredas jelly, is semisolid system consisting of two colloidal phases namely water and solid, and co-penetrated in liquid⁸. Gel preparation was chosen because it provides a feeling of comfort when used, does not clog pores, as well as has high elasticity thus enabling good skin breathability. Moreover, the dispersion of drug within gel preparation is excellent, brief and near perfect, thereby increasing the effectiveness of its usage as an anti-inflammatory agent. High water content means the moister the texture of the gel preparation, the better its ability to reduce heat and tension in given conditions²⁷.

 

Transdermal delivery, a successful novel approach aimed at achieving systematically active level of drug. The drug lornoxicam is a non-steroidal anti-inflammatory drug bearing analgesic, anti-inflammatory, and antipyretic property³⁵. When drug administration through other routes fails or skin infections occur, transdermal delivery system could be employed. Large numbers of dermal products are existing for skin as liquids, powders etc. However the most accepted products are semisolid preparation. Among the semisolid preparations, the transparent gels are utilized both in cosmetics and in pharmaceutical preparations. Gels were prepared by entrapment of large amounts of aqueous or hydroalcoholic liquid in a network of colloidal solid particles²³. Gel formulation provides better application property and stability in comparison to cream and ointment¹⁷. Topical gel drug administration is a localized drug delivery system anywhere in the body¹⁹. The gel formulation viscosity produces smooth penetration through the skin and release a drug⁴.

 

Based on this description, a research was conducted on the formulation of gel preparation of ethanol extract of Arbenan leaves [Duchesnea indica (Jacks.) Focke] as a pharmaceutically stable anti-inflammatory agent.

 

MATERIALS AND METHODS:

Sampling:

The sample used was the leaves of Arbenan [Duchesnea indica (Jacks.) Focke] taken from Mount Bawakaraeng, Gowa Regency, South Sulawesi.

 

Preparation Sample:

The collected Arbenan samples were cleaned of dirt adhering to the leaves using stream of water and then air-dried. After drying, the samples were crushed and collected for the extraction process²⁴.

 

Extraction Method:

Arbenanleaves powder was weighed as much as 300g, macerated with 2700mL ethanol, then allowed to stand for 3-4days while being stirred repeatedly, and then filtered to obtain liquid extract and residue. The liquid extract that has been obtained was evaporated with a Rotary Vacuum Evaporator at 50℃ to obtain a thick ethanol extract²⁰.

Formulation:

The composition of the Arbenan leaf extract gel preparation was carried out by optimizing the base gel formula to obtain the appropriate base based on the desired properties and characteristics of the gel. The master optimization carried out is:

 

Table 1: Composition of formulated gel preparations

Name of Ingredients	Concentration				Function
	F1 (% w/v)	F2 (% w/v)	F3 (% w/v)	F4 (% w/v)
Arbenan Leaf Extract	1,55	1,55	1,55	1,55	Active Substance
NaCMC	3	4	-	-	Gelling Agent
HPMC	-	-	8	9
Propylen glycol	5	5	5	5	Humectant
Peppermint oil	0,75	0,75	0,75	0,75	Penetration
Methyl Paraben	0,02	0,02	0,02	0,02	Preservative
Propyl paraben	0,02	0,02	0,02	0,02	Preservative
Aquadest ad	100	100	100	100	Solvent

 

The percentage of the extract used in the formula was based on the anti-inflammatory activity of the ethanol extract of Arbenan leaves, which is 0.31%¹⁸. Due to the influence of additives and other components in the preparation, the concentration of the extract was increased five times to increase its effectiveness.

 

Preparation of Gel Ethanol Extractof Arbenan Leaf:

The tools and materialsneeded were prepared beforehand, and all the ingredientswere weighed. NaCMC and HPMC were developed using a portion of the aquadest in the formula, made according to the concentration of each formula 1, 2, 3 and 4. Stirring was carried out at a certain speed using a homogenizer until a gel base was formed. After it was formed, propyl paraben and methyl paraben which had been dissolved in propyleneglycol were added, then peppermint oil was furtheradded, and the end result was homogenized. Next, the extract was dispersed into the base and homogenized. Lastly,the remaining aquadestwas added and homogenized¹⁰.

 

Characterization of Gel Extract of Arbenan Leaf:

a)    Organoleptic:

Organoleptic tests werecarried out visually on gel preparations which included the shape, color, and smell^38,3

 

b)    Homogeneity:

The preparation was placed between two glass objects and observed for coarse particles or inhomogeneity under light⁷.

 

c)     PH measurement:

PH examination of the gel preparation was carried out before and after the conditions were forced using a pH meter. The pH meter was dipped into the gel preparation up to the limit mark and the pH value would be read. The pH value of the mask preparation is 4.5 - 6.5³⁷.

 

d)    Spreadability Test:

About 0.5mL of the preparation was placed in a round glass, then another glass was placed on top of it, and it wasleft to stand for 1 minute. Weights of 50, 100, and 150gram were added subsequently, and the preparation was left to stand for 1 minute each time the weight was added. The end result was measured, and the resultingconstant diameter of the spreading power of 5-7 cm showing a semisolid consistency, which is very comfortable to use³⁹.

 

e)     Viscosity Test and Flow Properties:

Viscosity measurements were carried out using a Brookfield viscometer. The preparation was put into the measuring cup and then the appropriate spindle was lowered until the limit of the spindle was immersed in the preparation. Then the motor and spindle were turned on. Player speed was set to 10 successively; 20; 50; 60; and 100rpm then reversed from 100; 60; 50; 20; to 10rpm. The viscosity number indicated by the red needle was recorded. The viscosity value was calculated then the obtained data was plotted against shear pressure (dyne/cm2) and shear speed (rpm)³⁸.

 

f)     Preparation Stability Test:

Stabilityevaluation of the preparation was carried out before and after the conditions were applied, namely at a temperature of 5℃ and 35℃ alternately for 12hours each for 10 cycles and then repeated organoleptic tests, pH, homogeneity, spreadability, viscosity and flow properties were carriedout².

 

RESULT:

Characterization of Gel Extract of Arbenan Leaf:

a)    Organoleptic:

In organoleptic testing, the color, odor and consistency of each formula were observed. This test aims to determine whether there is a change in color, odor and consistency during storage before and after the forced conditions.

 

Table 2: Organoleptic Test Results of Arbenan Leaf Ethanol Extract Gel Before and After Forced Conditions

Formula	Test	Condition
		Before	After
F1	Color Odor Consistency	Dark brown Typical of mint Rather viscous	Dark brown Typical of mint Rather viscous
F2	Color Odor Consistency	Dark brown Typical of mint Viscous	Dark brown Typical of mint Viscous
F3	Color Odor Consistency	Dark brown Typical of mint Viscous	Dark brown Typical of mint Viscous
F4	Color Odor Consistency	Dark brown Typical of mint Very viscous	Dark brown Typical of mint Very viscous

 

b)    PH measurement:

PH testing was carried out to know whether the pH of the preparation meets the requirements of the skin pH range or not. The skin pH range is between 4.5-6.5⁶. The more alkaline or acidic the material gets on the skin, the more difficult it will be to neutralize it which couldexhaust the skin. If the pH of the preparation is below the pH range of the skin it will cause irritation and sensitivity problem, conversely, if the pH of the preparation is above the pH range of the skin it can cause dry and cracked skin³⁷.

 

Table 3: pH Test Results of Arbenan Leaf Ethanol Extract Gel Before and After Forced Conditions

Formula	Condition
	Before	After
1	4.99±0.006	5.04±0.032
2	5.19±0.006	5.13±0.023
3	6.21±0.006	6.16±0.005
4	6.22±0.001	6.14±0.005

 

c)     Homogeneity:

Homogeneity testing was carried out by observing the dosage forms under the light to detectany inhomogeneous particles. The purpose of this test is to see and to find out the mixing of gel preparation ingredients¹⁰.

 

Table 4: Homogeneity Test Results of Arbenan Leaf Ethanol Extract Gel Before and After Forced Conditions

Formula	Condition
	Before	After
1	Homogen	Homogen
2	Homogen	Homogen
3	Homogen	Homogen
4	Homogen	Homogen

 

d)    Spreadability Test:

The spreadability test aims to determine the ease of dispersion of Arbenan leaf ethanol extract gel preparations uponapplication to the skin¹¹. The greater the value of spreading power, the greater the ability to spread the preparation, and vice versa. Good gel spread ranges from 5-7 cm ⁴¹.

Table 5: Results of Spreadability Test of Arbenan Leaf Ethanol Extract Gel Before and After Enforced Conditions

Formula	Weight (g)	Gel Preparation (cm)
		Before	After
1	0 g	5.37±0.15	5.9±0.1
	50 g	5.87±0.15	6.73±0.25
	100 g	6.1±0.1	7.47±0.15
	150 g	6.2±0.1	7.8±0.1
2	0 g	4.27±0.15	4.13±0.15
	50 g	4.63±0.11	4.53±0.05
	100 g	5±0.1	4.97±0.05
	150 g	5.53±0.05	5.5±0.1
3	0 g	4.17±0.11	4.1±0.1
	50 g	4.6±0.1	4.57±0.05
	100 g	5.2±0.26	5.17±0.15
	150 g	5.53±0.11	5.53±0.15
4	0 g	4.17±0.2	4.1±0.15
	50 g	4.63±0.15	4.63±0.15
	100 g	5.13±0.2	4.83±0.2
	150 g	5.4±0.1	5.37±0.15

 

e)     Viscosity Test and Flow Properties:

The viscosity was directly dependent on the polymeric content of the formulations²⁵. Viscosity measurements were carried out to determine the amount of resistance to the flow of a system under the used pressure. Viscosity relates to the ease of application of the preparation to the skin. The higher the viscosity of the preparation, the more difficult it is to apply to the skin, conversely, the lower the viscosity of the preparation, the easier it is to apply to the skin. Viscosity was checked using a Brookfield viscometer. According to Elmitra (2017), the viscosity value of a good gel preparation is between 1000-100,000 cps⁹.

 

Table 6. The viscosity of Arbenan Leaf Ethanol Extract Gel

Formula	Viscosity of Gel Preparation (cPs)
	Before	After
1	9067±641.66	6267±46.18
2	17333±257.16	24800±288.44
3	18320±80	23440±576.88
4	17200±138	26213±454.89

 

The next step was the determination of flow properties. The purpose of determining flow properties is to characterize the process of pouring the dosage form from its container, pressing or squeezing the dosage form from a tube or other container that can change shape, rubbing and smearing the dosage form over the surface of the skin³¹. The type of flow can be seen after creating a rheogram that relates the shear stress and rate of share¹⁶.

 

Figure 1: Arbenan leaf ethanol extract gel rheogram with NaCMC Base 3% Before and After Conditions Forced

 

 

Figure 2: Arbenan leaf ethanol extract gel rheogram with NaCMC Base 4% Before and After Conditions Forced

 

 

Figure 3: Arbenan leaf ethanol extract gel rheogram with HPMC Base 8% Before and After Conditions Forced

 

Figure 4: Arbenan leaf ethanol extract gel rheogram with HPMC Base 9% Before and After Conditions Forced

 

DISCUSSION:

Inflammation is the body's protective response to tissue injury caused by physical trauma, chemicals, or microbiological agents²¹. The inflammatory process occurs when a tear in the skin and underlying tissue causes disruption of cells and the release of lipids from cell membranes. After membrane damage occurs, some cell membrane phospholipids such as macrophages, neutrophils, and mast cells, are broken down into arachidonic acid and factors that inactivate cell lysis. Arachidonic acid is metabolized by cyclooxygenase enzymes which produce prostaglandins. Prostaglandins cause several physiological effects including the increase of blood vessel permeability, vasodilation and stimulationof neutrophil chemotaxis, causing a feeling of heat, redness, swelling, and pain in the skin⁸.

 

Inflammation can be treatedwith synthetic drugs, one of which is the NSAID class of drugs³⁰. However, the use of synthetic drugs has adverse side effects. For this reason, the use of natural ingredients is proposed as an alternative solution because of its mild side effects. One of the plants that can be used as an anti-inflammatory drug is Arbenan [Duchesnea indica (Jacks.) Focke.]. According to Mursyid and Waris (2021), this plant has flavonoid compounds which are known to have biological activity as an anti-inflammatory agent¹⁸. Flavonoids work by blocking NF-kB activation. NF-kB is a transcription factor that produces cytokines and activates COX-2 as an anti-inflammatory effect^15,26.

 

Based on research by Mursyid and Waris (2021), the ethanol extract of Arbenan leaves effectively inhibits inflammation with a percent Anti-Inflammatory Power (DAI) of 0.31%¹⁸. This study aimed to formulate and evaluate a pharmaceutically stable ethanoic extract gel preparation of Arbenan [Duchesnea indica (Jacks.) Focke] leaves. The gel preparation was chosen because it gives a feeling of comfort when used, does not clog pores, and has high elasticity henceenabling good skin breathability. The dispersion of the drug through the gel preparation is also very good, brief, and near perfect, thereby increasing the effectiveness of using the gel as an anti-inflammatory agent. High water content means the moister in the texture of the gel preparation, the better it is in reducing heat and tension in the given conditions²⁷.

 

This plant extract was obtained through an extraction process using the maceration method because the content of flavonoid compounds would be damaged at temperatures above 50℃. After all, it can experience changes in its structure. Based on research Kurniatiet al., (2019) heating temperatures above 50 ℃ causes reduced levels of flavonoids contained in extracts and causes a decrease in the antioxidant activity of extracts¹³. In addition, maceration is the simplest method without heating so that the active compounds in the extract are still intact. The extract obtained was then formulated into a gel preparation. In this study, NaCMC and HPMC were used as gelling agents. Polymer derivatives are one of the gelling agents that are in great demand by formulators^5,34,1.

 

Initially, in this study, carbopol was used as the gelling agent. However, during the optimization process, the resulting consistency changed from thick to liquid. Ithappened because the phenolic compounds contained in the ethanol extract of Arbenan leaves triggered a change in consistency when the extract was added. Therefore, HPMC and NaCMC were chosen as gelling agents

 

NaCMC was chosen because it has good viscosity, is not toxic, and has good and wide spreadability. HPMC was chosen because it has good viscosity stability at temperature even though it is stored for a long time. In addition, HPMC has optimal physical stability, is non-toxic, has good resistance to microbial attack, and produces good spreadability on skin²⁸. As for the variations in the concentration used, respectively 3% and 4% for NaCMC, 8% and 9% for HPMC. This variation is used to optimize basic ingredients that effectively meet the criteria for the physical properties of pharmaceutical preparations and can survive the shelf life through stability tests.

 

Gel is a preparation that has a basic composition of water, therefore it is susceptible to the growth of microorganisms such as bacteria and fungi, so it needs addition of preservatives. The preservative used in the formula was a combination of compounds between methylparaben and propylparaben. The combination of the two can increase the effectiveness of the preservative so that the gel preparationcouldlast longer. According to Rowe et al. (2009) and Nisa (2016), methyl paraben and propyl paraben can inhibit a broad spectrum of para-microorganisms and can work effectively in a wide pH range^28,22. Propylene glycol as a humectant can maintain the stability of the preparation by trapping the surrounding moisture and preventing the water content in the preparation from evaporating²⁸.

 

Propylene glycol can also facilitate solubility for substances that are difficult to dissolve in water, because according to Rowe et al. (2009) propylene glycol can mix with water and alcohol²⁸. Peppermint oil can be used as a penetration enhancer. Peppermint oil can increase the delivery of active substances because it easily penetrates the skin and bloodstream and is easily excreted from the body through urine and feces. In addition, peppermint oil also gives a cold sensation when applied to the skin. The preparation process is carried out by mixing all the ingredients using a homogenizer. After the manufacturing process is continued by evaluating the preparations through stress condition stability tests, namely at 5℃ and 35℃ every 12hours for 10 cycles. The things observed in this test were organoleptic, pH, homogeneity, spreadability, and viscosity, and these tests were carried out before and after the conditions were forced. In organoleptic testing, the color, smell, and consistency of each formula were observed. This test aims to determine whether there is a change in the color, smell, and consistency of the preparation during storage before and after the forced conditions.

 

Based on the observations in table 2, the results were obtained before and after the forced conditions; for F1 it showed a dark brown color, a distinctive minty smell with a rather thick consistency. For F2 and F3 it was dark brown in color, has a distinctive mint smell and has a thick consistency, and for F4 it shows a dark brown color, has a distinctive mint smell and has a very thick consistency.The four formulas show no changes in terms of color, smell, and consistency.

 

Measurement of the pH of the preparation was carried out before and after the forced conditions were carried out to gauge the stability and safety of the preparation. From the measurement of pH before and after forced conditions, the results obtained were in F1 before forced conditions obtained a value of 4.99±0.006 and after forced conditions 5.04±0.032. For F2, the pH value was 5.19±0.006 before and 5.13±0.023 after the forced conditions. In F3, the pH value was 6.21±0.006 before and 6.16±0.005 after the forced conditions. And for F4 it shows a pH value of 6.22±0 before and 6.14±0.005 after forced conditions. Based on this description, each formula underwent a slight change wherein F1 experienced a slight increase in pH and F2, F3, and F4 experienced a decrease in pH. The difference in pH that occurred between NaCMC and HPMC was influenced by the concentrations used ineach agents. The base concentration used in NaCMCwas lower than the HPMC concentration. The increase and decrease in pH of the preparation were affected by temperature fluctuations and storage. Changes in the pH of the preparation during storage indicate instability during storage. Changes in the pH value will be affected by the temperature of decomposed media during storage which produces acids or bases. But all the pH of each formula is good to apply to the skin because it meets the skin's pH requirements.

 

From the homogeneous test results before the conditions were forced, the results for F1 were homogeneous preparations, F2 also showed homogeneity, and F3 and F4 also showed homogeneous preparations. This resultindicated that the preparation was well mixed after the process of mixing the formula ingredients. Then after the conditions were forced the results obtained by F1, F2, F3, and F4 showed a homogeneous preparation. This shows that there was no change in the homogeneity of the four preparations after stability testing.

 

The spreadabilitytest results wereobtained from the final diameter after the addition of the last weight where in F1 it shows 6.2±0.1cm before and 7.8±0.1cm after the forced condition. Results of F2 showed 5.53±0.05 cm before and 5.5±0.1 cm after forced conditions. The F3 results showed 5.53±0.11 cm before and 5.53±0.15 cm after forced conditions. In F4, the results were 5.4±0.1 cm before and 5.37±0.15 cm after forced conditions. Based on this description, F1 has met the dispersion requirements before the forced conditions and after that does not meet the dispersion requirements. As for F2, F3, and F4, they met the spreadability requirements both before and after the conditions were forced. This resultshows that the heavier the load, the greater the spreading power. In addition, the spreading power is also related to the viscosity where the higher the viscosity, the smaller the spreading power, and vice versa.

 

The viscosity of the preparations before and after the forced conditions changed, where there was a decrease in viscosity in F1 from 9067±641.66 cPs to 6267±46.18 cPs and for F2, F3, and F4 the viscosity increased. In F2 the results were from 17333±257.16 cPs to 24800± 288.44 cPs, for F3 from 18320±80 cPs to 23440± 576.88 cPs, and for F4 from 17200±138 cPs to 26213±454.89 cPs. Based on the description of the four formulas, they met the good viscosity requirements for gel preparations. One of the factors that increase and decrease viscosity is temperature. In the stability test, temperature fluctuations are given to cause an increase or decrease in viscosity. At high temperatures, the brown motion of the particles will increase and cause the forces between the particles to increase. Viscosity increases and decreases due to the collision of the brown motion between particles so that the distance gets smaller¹⁶.

 

From these results, the flow types in F1, F2, F3, and F4 have pseudoplastic flow. Flow is called pseudoplastic because according to Martin (2008), the pseudoplastic consistency curve starts at the point (0,0) or at least approaches the lowest shear velocity. In addition, the curve formed was also curved and did not show any linear curve parts. The curved curve in pseudoplastic is due to the action of pressure on the molecules of long-chain materials such as linear polymers. As the shear stress increases, the normally disordered molecules begin to align their long axes in the direction of flow. This orientation reduces the internal resistance of the material and results in a greater shear velocity at each shear stress. Based on this finding, the type of flow obtained by the two preparation bases is appropriate because according to Martin (2008) NaCMC and HPMC have a pseudoplastic flow type¹⁶.

 

CONCLUSION:

The conclusions from this study are:

1.     From the results of the research that has been conducted, it can be concluded that the ethanol extract of Arbenan leaves can be formulated into gel preparations using NaCMC and HPMC bases.

2.     Based on the results of conformity evaluation parameters of gel preparations, all formulations of Arbenan leaf ethanol extract gel preparations were pharmaceutically stable.

 

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this research.

 

ACKNOWLEDGMENTS:

The authors would like acknowledge Indonesian Ministry of education and Culutre, and faculty of Pharmacy, Universitas Muslim Indonesia.

 

REFERENCES:

1.      AVS Madhu Latha, J N Suresh Kumar, N Sojana, N Mounika, G Priyanka, A Venkatesh. Design and Optimization of Clotrimazole Emulgel by using various Polymers. Asian J. Pharm. Tech. 2021; 11(1):41-47.

2.      Banker, G. S. dan Rhodes, C. T. Modern Pharmaceutics 4th Edition.  Mercel Dekker, New York. 2002.

3.      B. Hemalatha, T. Pavani Priya, K. Manasa, Ch. Greeshmika, P. Kavya, Shaik Sayeeda Sarah, K. Padmalatha. Optimization of Oxiconazole Topical Emulgel Formulation for the Treatment of Skin Infections. Asian Journal of Pharmacy and Technology. 2022; 12(3):232-6.

4.      C. Kumaresan. Thumb arthritis treatment with diclofenac sodium Gel Formulation. Asian J. Res. Pharm. Sci. 2020; 10(4):239-240.

5.      D. R. Mundhada, A. V. Chandewar. An Overview on In-situ Gel. Res. J. Pharm. Dosage Form. and Tech. 2015; 7(4): 261-265.

6.      Daud, N.S., Akbar, A.J., Nurhikma, E., and Karmilah, K. Formulation of Snail Slime (Achatina Fulica) Anti-Acne Emulgel using Tween 80 - Span 80 as Emulsifying and HPMC as Gelling Agent. Borneo Journal of Pharmacy. 2018; 2(2): 64-67.

7.      Ditjen POM. Farmakope Indonesia. Ministry of Health of the Republic of Indonesia, Jakarta. 1979; 3rd Edition.

8.      Ditjen POM. Farmakope Indonesia. Ministry of Health of the Republic of Indonesia, Jakarta. 2020; 6th Edition.

9.      Elmitra. Dasar-dasarFarmasetika dan Sediaan Semi Solid. Deepublish, Yogyakarta. 2017: 162-164.

10.   Fatmawaty. TeknologiSediaanFarmasi. Yogyakarta: Deepublish, Yogyakarta. 2015.

11.   Garg, A., Aggarwal, D., Garg, S., and Singla, A.K. Spreading of semisolid formulations: An update. Pharmaceutical Technology North America. 2002; Vol.26, No.9: 84-105.

12.   Hui, J. X. Qiang, G.J. Wen, S.C. and Liu, X.M. High frequency shoot organogenesis in juvenile leaf of Duchesnea indica (Andr.) Focke. African Journal of Biotechnology. 2012; 11(17): 4039–4044. Doi: 10.5897/AJB11.3116.

13.   Kurniati, D., Arifin, H.R., Ciptaningtyas, D., dan Windarningsih, F. Study of Heating Effect on Antioxidant of Noni Fruit (Morindacitrifolia) as an Alternative of Funcional Food. Jurnal Teknologi  Pangan. 2019; 3(1): 20-25.

14.   Kusumawardhani, A. D., Kalsum, U. andRini, I. S. The Effect of Betel Leaf Extract Ointment (Piper betle Linn.) on the Number of Fibroblasts for Grade IIA Burns in White Rats (Rattus norvegicus) Wistar strain. 2015; 2: 13

15.   Lei, Z., Zhang, S.L., Tao, J.Y., Jin, F., Pang, R., Guo, Y. J., Ye. P. Dong, J.H. and Zheng, G.H. Anti-Inflammatory Mechanism of a Folk Herbal Medicine, Duchesnea indica (Andr) Focke at RAW264.7 Cell Line, Immunological Investigations. 2008; 37(4), 339–357. Doi: 10.1080/08820130802111589.

16.   Martin, A., Swarbrick J., dan Cammarata A. Physical Pharmacy. UI Press, Jakarta. 2008; 3rd Edition Book 2.

17.   Monika, Veena Rajput, Lija Prince. Effectiveness of Video Assisted Teaching Program on knowledge regarding Kegel exercise on Episiotomy pain and wound healing among nursing students of Durg District Chhattisgarh. Asian Journal of Nursing Education and Research. 2022; 12(1): 108-3.

18.   Mursyid, A. M dan Waris, R,. Aktivitas Antiinflamasi Ekstrak Etanolik Daun Arbenan [Duchesnea indica (Jacks.) Focke]. JurnalFitofarmaka Indonesia. 2021; 8(1): 18-22. Doi: 10.33096/jffi.v8i1.722.

19.   Mursyid, A. M dan Waris, R. Formulation and Evaluation of Pharmaceuticaly Stable Serum of Duchesnea Indica (Arbenan). Universal Journal of Pharmaceutical Research. 2021; 6(1): 38-42. Doi: https://doi.org/10.22270/ujpr.v6i1.538.

20.   Najib, A. EkstraksiSenyawaBahanAlam. Deepublish, Yogyakarta. 2018.

21.   Nardina, E.A, dkk. Farmakologi Dasar. Yayasan Kita menulis, Medan. 2021: 95.

22.   Nisa, Fakhrun. Patchouli Oil (PogostemoncablinBenth) Liquid Soap Formulation as Antibacterial against Stapylococcus aureus ATCC 25923. Pharmacy Study Program, UIN, Jakarta. 2016.

23.   N. Krishna Veni, P. Yashwanthi, B. Hemalatha, K. Padmalatha. A Review on Emulgels as a Novel Approach for Topical Drug Delivery. Asian Journal of Research in Pharmaceutical Sciences. 2022; 12(2):163-8

24.   Pratiwi, D. I. Syarif, R. A. Waris, R. and Faradiba. Isolasi Senyawa Antioksidan Ekstrak Metanol Kulit Buah Naga Merah (Hylocereuspolyrhizus). Jurnal Fitofarmaka Indonesia. 2019; 6(1): 340–346. Doi:10.33096/jffi.v6i1.466.

25.   Priyanka V Dhalkar, Shivani S Jagtap, Suraj T Jadhav, Myuresh R. Redkar., Biradev S Karande. Formulation and Evaluation of in situ Gel Model Naproxen. Asian J. Pharm. Tech. 2019; 9(3):204-207.

26.   Ridhayani, F., Lulu’ah, A., dan Hapsari, G, S. Anti-inflammatory via Inhibition of COX-2 on the NF-kB Line by Benzoquinone from Millipedes. UGM Faculty of Pharmacy, Yogyakarta. 2019.

27.   Rismana, E., Rosidah I., Praasetyawan Y., Bunga O., dan Erna Y. Effectiveness of the Efficacy of Treatment of Burns Gel Preparations Containing Centella asiatica Extract Fraction Based on Hydroxyproline and Histopathological Analysis on Rabbit Skin. Health Research Bulletin. 2013; 45-60.

28.   Rowe, C. R., Sheskey, P. J., dan Quinn, M. E. Handbook of Pharmaceutical Excipients Sixth Edition. Pharmaceutical Press, London. 2009.

29.   Santos, J.B.X., Silva, J.F., Passos, J.G.R., Gomes, J.A.S., Fernandes, J.M., Garcia, V.B., Junior, R.F.A., Zucolotto, S.M., Junior, A.A.S., Pedrosa, M.F.F. Development of an effective and safe topical antiinflammatory gel containing Jatropagossypiifolia leaf extract: results from a pre-clinical trial in mice. Journal of Ethnopharmacology. 2018; 227: 268-278. Doi: 10.1016/j.jep.2018.09.007

30.   Saputri, F.C dan Zahara, R. Anti-Inflammatory Activity Test of Basil Leaves Essential Oil (Ocimumamericanum L.) in Carrageenan-Induced Male White Rats. Pharm Sci Res. 2016; 3(3). Doi:10.7454/psr.v3i3.3619.

31.   Sinala, Santi. FarmasiFisik. Ministry of Health of the Republic of Indonesia, Jakarta. 2016.

32.   Srirod, S., dan Tewtrakul, S. Anti-inflammatory and wound healing effects of cream containing Curcuma mangga extract. Journal of Ethnopharmacology. 2019; S0378- 8741(18), 33813-3.

33.   Supriyatna, Febriyanti R. M, Dewanto, Wijaya, I, dan Ferdiansyah F. FitoterapiSistem Organ: Pandangan Dunia Barat TerhadapObat Herbal Global. Budi Utama, Yogyakarta. 2015.

34.   Shubham Tripathi, Somnath Patel, Ritesh Patel, Shraddha, Pushpendra, Sachin, Neetish, Mahendra, Kuldeep, Prashant, Rajesh Patel, Girish, Nitin, Tomanlal, Amrita Thakur, Mukta Agrawal, Ajazuddin, D. K. Tripathi, Amit Alexander. A Review on Biocompatible Hydrogel: Formulation Aspect and Evaluation. Res. J. Pharma. Dosage Forms and Tech. 2018; 10(2): 119-122.

35.   Sujata S. Sawant, Sangram S. Patil, Hemant S. Kandle, Manohar D. Kengar, Ganesh B. Vambhurkar, Mangesh A. Bhutkar. Development and Characterization of Lornoxicam loaded microsponge gel for Rheumatoid arthritis. Asian J. Pharm. Tech. 2019; 9(3): 173-178. doi: 10.5958/2231-5713.2019.00029.1

36.   Swapnil S Chopade, Esther Gaikwad, Nikhil Patil, ArehalliManjappa, John Disouza. Development of Topical Nanogel as a Promising Delivery of NSAID’s Tenoxicam using Natural Permeation Enhancer Essential Oil (Euckolyptus). Asian Journal of Pharmacy and Technology. 12(4): 299-4.

37.   Traggono, R. I, Latifah, Fatmah. Buku Pegangan Ilmu PengetahuanKosmetik. PT. Gramedia Pustaka Utama, Jakarta. 2007.

38.   USP. The United States Pharmacopeia. USP 36/ The National Formulary NF 31. Rockville: The United States Pharmacopeia Convention. 2012.

39.   Voight, R. Pharmaceutical Technology. UGM Press, Yogyakarta. 1994.

40.   Zhang, Y., Xia, Q., Li, Y., He, Z., Li, Z., Guo, T., Wu, Z., Feng, N. CD44 assists the topical antipsoriatic efficacy of curcumin-loaded hyaluronanmodifiedethosomes: a new strategy for clustering drug in inflammatory skin. Theranostic. 2019; 9(1): 48-64.

41.   Zubaydah, W.O.S., Wahyuni, W., Sahidin, S., Halik, T.A., Andriani, R., Indalifiany, A., and Fristiohady, A. Anti-inflammatory Activity of Pharmaceutical Gel of Ethanolic Extract from Marine Sponge Xestospongia Sp. Borneo Journal of Pharmacy. 2019; 2(1): 1-9. Doi: 10.33084/bjop.v2i1.694,

 

 

 

 

Received on 14.12.2022         Modified on 17.05.2023

Accepted on 14.09.2023   ©AandV Publications All Right Reserved