Optimization of the Drying Process of Ethanol Extract of Gayam Seeds

(Inocarpus fagiferus Fosb) for the Preparation Formula Powders

and Granule of Standardized Herbal Medicine Antiatherosclerosis

I Made Sukadana¹, Sri Rahayu Santi², Ketut Widnyani Astuti³, N. N. Rupiasih⁴

¹Chemistry Department, Faculty Mathematics and Natural Sciences Udayana University, Bali, Indonesia.

²Chemistry Department, Faculty Mathematics and Natural Sciences Udayana University, Bali, Indonesia.

³Pharmacy Department, Faculty of Mathematics and Natural Sciences Udayana University, Bali, Indonesia.

⁴Physic Department, Faculty Mathematics and Natural Sciences Udayana University, Bali, Indonesia.

*Corresponding Author E-mail: im_sukadana@unud.ac.id, sr_santi@unud.ac.id, ketutwidyani@unud.ac.id, rupiasih@unud.ac.id

ABSTRACT:

Antioxidant preclinical test, SOD activity, lipid profile, MDA, and in vivo test using biomarkers ICAM-1, SOD-2, SOD-3, TNF-α, and IL-6 aortic endothelial cells, as well as acute and subchronic toxicity test on the liver and kidney of hypercholesterolemic Wistar rats has been carried out on the ethanol extract of Gayam seeds (Inocarpus fagiferus Fosb). The dose of Gayam seed ethanol extract as an anti-atherosclerosis which was concluded from several preclinical tests using this biomarker was 50mg/kg body weight. The next step is to formulate the ethanol extract of Gayam seeds as a standardized anti-atherosclerotic herbal medicine. Extracts as medicinal preparations before formulation must be dried optimally using pharmaceutical excipients that can attract the liquid content contained in the extract so that the extract becomes dry. The ratio of drying agent and extract greatly determines the nature of the preparation material to be formulated. Extract drying optimization uses a ratio of extract composition to Aerosil® as a drying agent, namely: 1:0.25; 1:0.50; 1:0.5; 1:0.75; 1:1; and 1:2 which are hereinafter referred to as formulas 1, 2, 3, 4, and 5 respectively. Each formula was dried using an oven at 40°C for 24 hours. The results of the dry extract of each formula were then sieved using a mesh sieve no. 20 and testing the moisture content (MC) as well as observing the characteristics of the powder properties of the formula. The results showed that formulas 4 and 5 were optimal dry preparations because the results of the measurement of moisture content (MC) were below 5%, namely formula 4 of 4.20±0.20% and formula 5 of 3.81±0.10%. The flow properties of a powder were observed using 2 methods, namely flow time and angle of repose, where formulas 4 and 5 have a flow time of 5.48±0.52 and 6.51±0.55g/sec, and an angle of repose of 28, respectively. 47±2.25 and 29.77±2.18 degrees. Both formulas have good flow properties because they have flow times in the range of 4-10g/sec and the angle of repose formed is also in the range of 20-30 degrees. Measurements of real specific gravity and compressed specific gravity for formulas 4 and 5 showed data that were not significantly different, so the compressibility value was calculated where the compressibility value was in the range of 12-16% indicating that the flow properties of the powder were good. Based on the results of the study, it was concluded that the addition of Aerosil® to extracts with a composition of 1:1 (formula 4) produced a dry extract in the form of a powder with good flow characteristics which could then be developed as a powder/solid preparation material for further formulation.

KEYWORDS: Gayam seed extract, Antiatherosclerosis.

INTRODUCTION:

Gayam seeds (Inocarpus fagiferus Fosb) or in Bali known as gatep^1,2 have the potential as an ingredient to prevent atherosclerosis. This potential is supported by preclinical antioxidant data from ethanol extract which can inhibit DPPH radicals at an IC50 of 280ppm, increase the SOD activity of Wistar rat blood plasma, and improve the condition of lipid profiles such as total cholesterol, triglycerides, LDL, and HDL. The antioxidant potential of ethanol extract from gayam seeds is due to the chemical content of linoleic acid, ethyl linoleate, ethyl oleate, and homopterocarpine³. Gayam seed ethanol extract has also been shown to increase SOD-3 expression in aortic endothelial cells and reduce MDA levels in the blood plasma of Wistar rats, which is indicated to prevent atherosclerosis⁴. The exogenous antioxidant potential of the ethanol extract of Gayam seeds is thought to trigger the endogenous antioxidant SOD, especially SOD-2, which can be expressed in aortic endothelial cells as an anti-atherosclerosis biomarker^5,6,7,8,9,10. The condition of aortic endothelial SOD-2 expression influences the expression of aortic endothelial ICAM-1 so that ICAM-1 can be used as a biomarker for early detection of atherosclerosis. The ability to reduce blood plasma MDA levels from ethanol extract of gayam seeds is related to inflammatory mechanisms as proven in the expression of TNF-α and IL-6 in aortic endothelial cells¹¹. Preclinical tests on the biomarkers ICAM-1, SOD-2, TNF-α and IL-6 in aortic endothelial cells have been carried out¹² as well as acute and subchronic toxicity effects on the liver and kidneys of hypercholesterolemic Wistar rats. The dose of ethanol extract of Gayam seeds as antiatherosclerosis concluded from several preclinical tests using the biomarkers SOD, SOD-2, SOD-3, MDA, ICAM-1, IL-6, and TNF-α is 50 mg/kg bw. This dose then needs to be formulated as a standardized herbal medicine for anti-atherosclerosis. The anti-atherosclerosis ethanol extract formulation process requires dry optimization of the extract before it is formulated as a solid tablet or granule as a capsule preparation¹³. Tests for determining the physical properties of formulation preparation materials are reported in this paper.

MATERIAL AND METHODS:

Material:

The plant material used in this research is style seeds obtained from the Tabanan area of Bali and have been determined.

The chemical used in this research was Ethanol 96% EMSURE ®Reag. Ph Eur Merck Cat. 1.59010.2500, Avicel PH- 101 Sigma Aldrich Cat. 11365-1KG, Avicel PH- 101 Sigma Aldrich Cat. 11365-1KG, Starch Soluble Gr For Analysis Iso Merck Cat. 1.01252.1000, Parteck Lub MST (Magnesium Stearate Vegetable Grade) EMPROVE®ESSENTIAL Ph Eur, BP, JP, NF, FCC, Merck Cat. 1.00663.9020, Sodium carboxymethylcellulose, Sigma Aldrich CAS Number: 9004-32-4, Capsule shell no. 0 Brataco Chemika, and aquamineral.

The equipment used in the research includes a set of glassware, blender, sieve, extractor, rotary vacuum evaporator, centrifuge, analytical balance, dropper pipette, measuring flask, Eppendorf tube, TEQ bj2 disintegrator tester, manual granule flow tester, capsule filler, oven, and climatic chamber.

Methods:

Preparation of ethanol extract of gayam seeds as a standardized herbal medicine for anti-atherosclerosis:

Gayam seeds are dipped in hot ethanol and drained. The seeds are cleaned of dirt and moss, then cut into small pieces and dried by placing them in the open air and not exposed to direct sunlight. Next, the dried gayam seeds are made into powder by grinding them using a blender. Gayam seed powder is weighed and ready to be extracted.

A total of 5kg of dry gayam seed powder was macerated with ethanol pa in a dark extractor bottle and at room temperature for 24hours. The extract is filtered, while the dregs are macerated again with ethanol until the compounds contained therein are completely extracted. The filtrate obtained was evaporated using a rotary vacuum evaporator to obtain a concentrated ethanol extract and weighed. The concentrated ethanol extract is then made in solid or powder and granular preparations starting with dry optimization of the extract, determining the physical properties and quality of the solid/powder and granules.

Optimization of Dried Powder Gayam Seed Extract:

First, dry the concentrated ethanol extract of gayam seeds using Aerosil with various compositions which is hereinafter referred to as Formula as shown in the following table:

Table 1. Composition extract and Aerosil^® or formula

Formula	Extract	Aerosil^®
1	1.00	0.25
2	1.00	0.50
3	1.00	0.75
4	1.00	1.00
5	1.00	2.00

Each of the compositions above i.e; Formula 1(F1), Formula 2(F2), Formula 3(F3), Formula 4(F4), and Formula 5(F5), was measured for moisture content (MC). Based on moisture content (MC) testing, an MC result below 5% is a good composition or in other words optimal drying. The characteristics of the powder were tested using several parameters, namely organoleptic, flow time and angle of repose, real and compressible specific gravity, and compressibility.

Optimization of Granules Gayam Seed Extract:

Weigh all the necessary ingredients. First, dry the gayam seed extract using Aerosil® separately (Mixture I). In a different place, mix the Manihot starch, lactose, and pvp k30 in a mortar while grinding until homogeneous (Mixture II). Then add Mixture I geometrically to Mixture II while grinding until homogeneous. Add distilled water drop by drop while grinding until a mass is formed that can be clenched, then extruded using sieve no. 10. Dry the mass obtained in the oven at a temperature of 500C until a drying shrinkage (LOD) level of between 2-5% is obtained, measured using a moister balance device. The dried coarse granules were then sifted again using sieve no. 20 to obtain a more uniform granule size. Next, the granules obtained are subjected to physical properties tests to determine the quality of the granules that have been made. Record all data obtained and analyzed.

RESULT AND DISCUSSION:

Optimizing and Testing Physical Properties of Powder:

A total of 5 kg of dry gayam seed powder was macerated with 5 x 2.5 L of 96% ethanol solvent to produce a concentrated brown ethanol extract of 26.03 g. Extract was dried with Aerosil to protect active ingredients from moisture, increase homogeneity and avoid dampness due to reaction between ingredients¹⁴. Aerosil is commonly used method for converting a wide range of liquid extracts into powder form. This process results in powders of good quality, low water activity and makes it easy for transport and storage. Powders obtained by spray drying shows problems like stickiness, hygroscopicity. When powders stick on the dryer chamber wall during drying, and which reduces % yield of product and also it can causes operational problems. Stickiness depends on temperature and moisture content. If amorphous powders are at temperatures and/or moisture contents higher then particles sticks with another particle. Aerosil is high molecular weight substances with high glass transition temperatures so it minimizes sticking¹⁵. Powder characteristics such as moisture content was examined in this study to optimize the drying operating conditions¹⁶.

The concentrated extract after making various formulas as shown in Table 1, the results of measuring the moisture content (MC) of various extract and Aerosil® or formula are presented in Table 2 as follows:

Table 2. Moisture content (MC) measurement results for various formulas

Formula	Moisture Content (%)
F1	9.34 ± 0.45
F2	7.56 ± 0.23
F3	6.48 ± 0.11
F4	4.20 ± 0.20
F5	3.81 ± 0.10

Based on Table 2, it appears that the drying process takes place optimally with the composition of using extracts with Aerosil® 1:1 or F4 and 1:2 or F5. This is proven by the MC value which is already below 5%¹⁷. The powder content that is good for the pharmaceutical preparation formulation process is below 5%. This is because if it is above this value, the powder will become damp and will be susceptible to the growth of microorganisms or the low value of moisture content could prevent bacterial, fungal or yeast growth^18,19. On the other hand, if the powder is too dry, during the formulation process, the powder will break easily and the hydrophobic properties will increase. This causes the powder to be more difficult to dissolve. Based on these results, F4 and F5 were then continued to measure the powder characteristics. The characteristics of the powder were tested using several parameters, namely organoleptic, flow time and angle of repose, real and compressible specific gravity, and compressibility²⁰. The observation results can be seen in Figure 1 and Table 3.

Figure 1. Organoleptic powder based on selected formula

Based on observations, both compositions have the same color and shape, namely cream color and powder form. This shows that the addition of drying agents to various compositions does not cause color changes. The brown extract turns cream due to the addition of white excipients. However, increasing the concentration does not have any effect on the resulting product.

Table 3. Observation results of physical characteristics of powder based on selected composition (F4 and F5)

Parameter	F4	F5
Flow rate (g/s)	5.48±0.52	6.51±0.55
Angle of repose (º)	28.47±2.25	29.77±2.18
Real specific gravity (g/mL)	0.053±0.000	0.053±0.000
Incompresible specific gravity (g/mL)	0.064±0.000	0.065±0.001
Compressibility (%)	15.98±0.54	15.90±0.53

The flow properties of a powder can be observed using 2 methods, namely flow time and angle of repose. Based on the data above, Formulas 4 and 5 both have flow times in the range of 4-10g/second. Apart from that, the angle of repose formed is also in the range of 20-30 degrees^21,22. This shows that both formulas have good flow properties. The drying process that occurs shows good results so that there is no adhesion between one particle and another. This causes the powder to flow easily²³. The flowability of a powder is an important property influencing several drug manufacturing steps. Flowability is affected by the physical properties of the powder, such as particle size and shape, the loading experienced by particles (gravity, interaction with air flow and container etc.), the current state of the powder (i.e. tap, free flowing etc.) and the processing environment (e.g. humidity). Particles larger than 250 µm usually flow freely while particles below 100 µm are generally cohesive and prone to flowability problems²⁴.

The real specific gravity and compressible specific gravity can be observed in the table above. Based on this data, Formulas 4 and 5 produce data that is not significantly different. From this data, the compressibility value is then calculated. Based on calculations, the compressibility value is in the range of 12-16%, which indicates that the powder flow properties are good²³. This shows that the dried extract has produced a powder with good flow properties. Extracts that have been dried maximally and produce powder with good flow characteristics will make it easier to formulate the dosage form^25,26.

Based on the observations above, it can be concluded that by adding Aerosil® to the extract with a composition of 1:1, it can produce a dry extract in the form of powder with good flow characteristics. Formula 4 can then be further developed to be formulated into pharmaceutical preparations, especially solid dosage forms.

Optimizing and Testing Physical Properties of Granules

The granule was made with wet granulation technique³². Granules are used to lower dust during the granulation process to reduce toxic exposure and process-related hazards, to improve the appearance of the product, to facilitate metering or volumetric dispensing, to increase the density of the blend so that it occupies less volume per unit weight for better storage and shipment, and to improve the uniformity of the active ingredients performance in the final product²⁷. The granule formula is made in three formulations, namely Formula 1 (F1), Formula 2 (F2), and Formula 3 (F3). Formula 1 (F1) was not continued because F1 was too wet so it was difficult to determine its physical properties. The results of the wet F2 and F3 granules before sieving and the dry granules after sieving are shown in Figure 2. Several test parameters were carried out to determine the physical properties of granules, namely organoleptic tests, drying shrinkage tests, flow rate and angle of repose tests, real specific gravity and compressible specific gravity tests, as well as capsule weight uniformity tests. The organoleptic test results and observations of the physical characteristics of the granules for Formula 2 (F2) and Formula 3 (F3) are presented in Tables 4 and 5.

Table 4. Granule Organoleptic Test Results

Sifat Organoleptic	F2	F3
Color	Brown	Brown
Form	Round	Round
Flavor	Tasteless	Tasteless
Smell	No smell	No smell

Table 5. Observation results of granule physical characteristics

Parameter	F2	F3
Moisture content (%)	5.0	3.16
Flow rate	Very good	Very good
Angle of repose (º)	26.08	27.71
Real specific gravity (g/mL)	0.62	0.49
Incompresible specific gravity (g/mL)	0.72	0.57
Compressibility (%)	14.29	13.95

Table 6. Test the uniformity of capsule weight

Average Weight Capsule Contents	Differences in Capsule Content Weights (%)
Average Weight Capsule Contents	A	B
120 mg or more	10	20
More than 120 mg	7.5	15

The particle size distribution (PSD) of a powder defines the relative amounts of particles present, sorted according to size. The flow properties of particulate solids are also known to depend on the size distribution of particles ^{28,29, 33}

For F2 the largest weight of each capsule in column A is 5.37%. The largest weight of 2 capsules in column B is 5.37% + 4.57% = 9.94% and for F3 the largest weight of each capsule in column A is 4.52%. The largest weight of 2 capsules in column B is 4.52% + 3.52% = 8.04%. The best granule optimization is Formula 2 (F2) and Formula 3 (F3) because it meets the requirements for the physical properties of the granules^30,31,34.

CONCLUSION:

Optimization of dry extracts using Aerosil® shows that Formula 4 (F4) can be developed to be formulated into pharmaceutical preparations, especially powder dosage forms, while the best granule optimization is Formula 2 (F2) and Formula 3 (F3) because it meets the requirements for the physical properties of the granules.

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Received on 05.07.2024 Revised on 08.10.2025

Accepted on 13.05.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):2903-2908.

DOI: 10.52711/0974-360X.2026.00414

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.


Wet granules before sieving	Wet F2 granules after sieve No. 10	Wet F3 granules after sieve No. 10	Dry granules after sieve No. 20