Optimization of Myristica fragrans Nanoemulgel Formulation Based on a Low-Energy Method of Preparation and Simplex Lattice Design
Khadijah Zai*, Maria Indra Ardriyanto, and Annisa Najwa HanifahAbstract Nutmeg (Myristica fragrans), a plant native to Indonesia, offers a range of health benefits, including mild analgesic effects. One effective way to deliver nutmeg oil for pain relief is to apply it topically. In this context, nanotechnology, specifically nanoemulgel, provides an ideal formulation for enhancing the therapeutic properties of nutmeg oil. Nanoemulgel enables the oil to penetrate the skin more efficiently, resulting in greater stability. A key factor in developing an effective nanoemulgel is selecting the right combination of surfactants and cosurfactants. These components are crucial for optimizing the formulation and achieving the desired characteristics of nanoemulsion. This study aims to develop a nutmeg oil nanoemulgel by determining the most effective composition for the nanoemulsion. To identify the optimal formula, we employed a low-energy method in combination with simplex lattice design (SLD). This approach allowed the systematic evaluation of various formulation parameters to find the best combination for nutmeg oil nanoemulgel. Based on the results, the optimum formula of nutmeg oil nanoemulgel had a mixing ratio of surfactant (Tween 80) and co-surfactant (PEG400) in 23:17 (w/w), droplet size distribution of 142.66 ± 7.36 nm, polydispersity index (PdI) of 0.247 ± 0.015, and potential zeta of -0.10 ± 0.28 mV. The optimal formula of the nutmeg oil nanoemulsion demonstrated stability after centrifugation, as evidenced by droplet size and PdI measurements of 263.36 ± 5.49 nm and 0.252 ± 0.01, respectively. The nanoemulgel, the final dosage form, exhibited a viscosity value of 9041.5 ± 278.77 cP.
Keywords: Simplex lattice design, Nutmeg oil, Myristica fragrance, Nanoemulsion, Nanoemulgel
Citation: Zai, K., Ardriyanto, M.I., and Hanifah, A.N. 2026. Optimization of Myristica fragrans nanoemulgel formulation based on a low-energy method of preparation and simplex lattice design. Natural and Life Sciences Communications. 25(3): e2026058.
Graphical Abstract:

INTRODUCTION
The bioactive components in nutmeg oil (Myristica fragrans) have been demonstrated to possess a range of beneficial properties, including potential analgesic and anti-inflammatory effects (Warsito, 2021). The application of nanotechnology in drug delivery systems, such as nanoemulgel, can be utilized to prepare nutmeg oil preparations. Nanoemulgel is a mixture of a nanoemulsion and a gelling agent, prepared by incorporating the nanoemulsion into a gel base (Morteza-Semnani et al., 2022). A nanoemulsion can be defined as a dispersion system consisting of oil, water, surfactant, and cosurfactant phases (McClements, 2013). The preparation of a nanoemulsion entails mixing two distinct phases, namely an oil phase and a water phase, to form droplets with diameters ranging from 20 to 500 nm (Narawi et al., 2020). Recent studies have also highlighted that nanoscale systems significantly enhance skin permeation and bioactivity of therapeutic compounds (Singpanna et al., 2023; Saravanan et al., 2025).
Nanoemulgel offers several advantages, including high viscosity, which facilitates ease of application, enhances adhesion, and improves formulation stability. In addition, nanoemulgels can modify the concentration gradient between the gel matrix and the skin, thereby influencing drug penetration (Jeengar et al., 2016; Eid et al., 2021). One commonly used gelling agent is Carbopol 940, which helps regulate the release of active ingredients from drug formulations (Ajazuddin et al., 2013). Recent studies further support these benefits. For example, Muñoz et al. (2023) developed lemon essential oil nanoemulgels using pectin, demonstrating favorable physical stability and rheological properties. Yap et al. (2024) highlighted the potential of plant-based nanoemulgels for cosmeceutical applications, particularly regarding stability, skin compatibility, and functional performance. Advances in statistical optimization approaches, such as Design of Experiments (DoE), have also contributed to improved formulation performance and therapeutic outcomes. A Melissa officinalis-loaded nanoemulgel optimized using DoE showed enhanced anti-inflammatory activity and physicochemical stability (Koushik et al., 2025), while a Cananga odorata essential oil nanoemulgel demonstrated promising functionality, stability, and antimicrobial activity for topical scalp applications (Alam et al., 2024).
One commonly used gelling agent is Carbopol 940, which helps regulate the release of active ingredients from drug formulations (Ajazuddin et al., 2013). Therefore, this study aims to determine the optimal nanoemulsion formula, which will be combined with Carbopol 940 to create a nanoemulgel. The characteristics of the resulting nanoemulgel will be evaluated, including its organoleptic properties, droplet size distribution before and after the formation of the nanoemulgel, and its viscosity.
MATERIALS AND METHODS
Materials
Nutmeg (Myristica fragrans) oil was purchased from PT. Darjeeling Aroma Alami, Indonesia. Polysorbate 80 (Tween 80) was obtained from Industria Chimica Panzeri, and PEG 400 was purchased from Fred Homberg & Co. Carbopol 940 was obtained from Lubrizol. Glycerin, methyl paraben, propyl paraben, and triethanolamine were of pharmaceutical grade and used as received.
Tween 80 was selected as the surfactant due to its non-ionic nature, high safety profile for topical use, and hydrophilic–lipophilic balance (HLB ≈ 15), which is suitable for forming oil-in-water nanoemulsions. PEG 400 was chosen as a cosurfactant to enhance interfacial fluidity and reduce interfacial tension, facilitating nanoemulsion formation. Carbopol 940 was used as the gelling agent because of its high viscosity, stability, and suitability for topical formulations.
Pseudo-ternary phase diagram construction
A pseudo-ternary phase diagram was constructed using the water titration method to determine the appropriate composition range for nanoemulsion formation. Surfactant–cosurfactant mixtures (Smix) consisting of Tween 80 and PEG 400 were prepared at ratios of 1:1, 2:1, and 3:1 (w/w). These ratios were selected to evaluate the influence of hydrophilic–lipophilic balance on nanoemulsion formation and stability.
Nutmeg oil combined with menthol (total oil phase 20%) was mixed with Smix according to predetermined proportions. The mixture was homogenized using a vortex mixer at 2,000 rpm for 2 min. Distilled water was then added dropwise while continuously homogenizing to facilitate phase transition and nanoemulsion formation.
The resulting systems were visually observed and analyzed for droplet size and polydispersity index (PdI) using dynamic light scattering (Particle Size Analyzer). The obtained data were plotted in a pseudo-ternary diagram to determine the nanoemulsion region and the upper–lower limits of each component.
Optimization of nutmeg nanoemulsion formula
Optimization was performed using a simplex lattice design (SLD) to evaluate the effect of surfactant and co-surfactant composition on nanoemulsion characteristics. The experimental runs and composition ratios generated by the SLD are presented in Table 1. The design systematically varied the proportions of Tween 80 and PEG 400 while maintaining the oil phase concentration at 20% (w/w).
The low-energy phase inversion composition (PIC) method was employed because it minimizes thermal stress and is suitable for essential oil formulations. The oil phase (nutmeg oil and menthol) was first mixed with the surfactant–co-surfactant mixture (Smix) according to the ratios shown in Table 1 and homogenized using a vortex at 2,000 rpm for 2 min. Distilled water was then added gradually under continuous mixing to induce phase inversion and nanoemulsion formation. The formation of nanoemulsion was indicated by a transparent or slightly bluish appearance.
Table 1. Ratio combination of tween 80 and PEG 400 generated by SLD.
|
Run |
Composition ratio (%, w/w) |
% Oil |
|
|
Tween 80 |
PEG (400) |
||
|
1 |
30.0 |
10.0 |
20 |
|
2 |
22.5 |
17.5 |
|
|
3 |
27.5 |
12.5 |
|
|
4 |
25.0 |
15.0 |
|
|
5 |
20.0 |
20.0 |
|
|
6 |
20.0 |
20.0 |
|
|
7 |
25.0 |
15.0 |
|
|
8 |
30.0 |
10.0 |
|
Characterization of nutmeg nanoemulsion and nanoemulgel
Droplet size and size distribution analysis
Droplet size and PdI were measured using the dynamic light scattering (DLS) method. Samples were diluted threefold with distilled water before analysis, and 200 µL of the diluted sample was used for measurement.
Thermodynamic stability test
Thermodynamic stability was evaluated by centrifugation at 10,000 rpm for 30 min to assess resistance to phase separation. Samples were subsequently analyzed for droplet size and PdI.
Determination of the optimum nutmeg nanoemulsion formula
The optimum formulation was determined using SLD based on response parameters, including droplet size and PdI, before and after centrifugation. The target criteria were droplet size of 20–200 nm and PdI < 0.3 to ensure nanoemulsion homogeneity and stability.
Verification of the nutmeg nanoemulsion formula
The predicted optimum formulation was prepared according to SLD results and characterized for droplet size and PdI before and after centrifugation. Experimental values were compared with predicted values using a single-sample t-test at a 95% confidence level.
Nutmeg nanoemulgel preparation
Nutmeg nanoemulgel was prepared by incorporating 75% nanoemulsion into 25% gel base. The composition of the gel base is presented in Table 2. Carbopol 940 was selected as the gelling agent due to its high viscosity, stability, and suitability for topical delivery systems. The gel base was prepared by dispersing Carbopol 940 in distilled water under continuous stirring until homogeneous. Methyl paraben and propyl paraben, previously dissolved in warm water, were then added as preservatives, followed by glycerin as a humectant. The pH was adjusted to 6–7 using triethanolamine to obtain optimal gel consistency and skin compatibility. The gel base was allowed to hydrate for 24 h before nanoemulsion incorporation. Subsequently, the nanoemulsion was added gradually into the gel base under gentle stirring at 100 rpm for 15 min to obtain a homogeneous nanoemulgel.
Table 2. Gel-based formulation.
|
Materials |
Concentration (% w/w) |
|
Carbopol 940 |
1 |
|
Glycerine |
20 |
|
Methyl paraben |
0.72 |
|
Propyl paraben |
0.08 |
|
Triethanolamine (TEA) |
adjust pH |
|
Water |
add to 100 |
RESULTS
Pseudoternary phase diagram construction
A pseudoternary phase diagram was constructed to determine optimal ratios of oil (nutmeg oil + menthol), water, and surfactant/cosurfactant mixtures (Smix) for nanoemulsion formation. Smix ratios of Tween 80 to PEG 400 (1:1, 2:1, 3:1) were evaluated, yielding HLB values of 13.30, 13.87, and 14.15, respectively. Based on droplet size and polydispersity index (Tables 3 and 4; Figure 1), the combination of 40% Smix, 40% water, and 20% oil was chosen for further formulation development.
Table 3. Nutmeg oil droplet size distribution in nanoemulsion based on pseudoternary diagram phase (N=5).
|
No |
Smix (%) |
Water (%) |
Oil (with menthol) (%) |
Particle size (nm) |
||
|
Smix 1:1 |
Smix 2:1 |
Smix 3:1 |
||||
|
1 |
75 |
5 |
20 |
403.6 ± 112.80 |
27.79 ± 6.40 |
35.71 ± 4.87 |
|
2 |
70 |
10 |
20 |
3,714 ± 99.85 |
30.76 ± 3.33 |
23.89 ± 3.74 |
|
3 |
65 |
15 |
20 |
7,131.4 ± 699.59 |
21.19 ± 2.44 |
25.36 ± 7.71 |
|
4 |
60 |
20 |
20 |
3,089.8 ± 939.40 |
19.54 ± 1.00 |
26.48 ± 3.47 |
|
5 |
55 |
25 |
20 |
306.08 ± 6.58 |
34.83 ± 3.21 |
22.03 ± 1.17 |
|
6 |
50 |
30 |
20 |
350.02 ± 18.65 |
221.01 ± 99.34 |
21.29 ± 1.19 |
|
7 |
45 |
35 |
20 |
193.08 ± 2.19 |
124.94 ± 4.52 |
31.16 ± 1.94 |
|
8 |
40 |
40 |
20 |
213.04 ± 4.36 |
226.42 ± 4.57 |
31.59 ± 0.70 |
|
9 |
35 |
45 |
20 |
|
147.90 ± 5.80 |
46.58 ± 0.74 |
|
10 |
30 |
50 |
20 |
|
|
503.5 ± 120.70 |

Figure 1. Physical appearance of nutmeg oil nanoemulsion by using Smix ratio a) 1:1, b) 2:1, and c) 3:1. The total amount of Smix in the formula was gradually decreased from left to right (75% to 5%).
Table 4. Polydispersity index of nutmeg oil droplet in nanoemulsion based on Pseudoternary diagram phase (N=5).
|
No |
Smix (%) |
Water (%) |
Oil (with menthol) (%) |
Polydispersity index (PdI) |
||
|
Smix 1:1 |
Smix 2:1 |
Smix 3:1 |
||||
|
1 |
75 |
5 |
20 |
0.993 ± 0.01 |
0.330 ± 0.06 |
0.321 ± 0.05 |
|
2 |
70 |
10 |
20 |
0.819 ± 0.17 |
0.302 ± 0.04 |
0.348 ± 0.06 |
|
3 |
65 |
15 |
20 |
0.501 ± 0.29 |
0.406 ± 0.06 |
0.384 ± 0.09 |
|
4 |
60 |
20 |
20 |
0.408 ± 0.18 |
0.370 ± 0.03 |
0.316 ± 0.06 |
|
5 |
55 |
25 |
20 |
0.106 ± 0.01 |
0.319 ± 0.02 |
0.419 ± 0.05 |
|
6 |
50 |
30 |
20 |
0.119 ± 0.06 |
0.538 ± 0.11 |
0.538 ± 0.11 |
|
7 |
45 |
35 |
20 |
0.179 ± 0.01 |
0.485 ± 0.01 |
0.593 ± 0.07 |
|
8 |
40 |
40 |
20 |
0.118 ± 0.03 |
0.221 ± 0.01 |
0.469 ± 0.01 |
|
9 |
35 |
45 |
20 |
|
0.197 ± 0.02 |
0.500 ± 0.01 |
|
10 |
30 |
50 |
20 |
|
|
1.000 ± 0.01 |
Preparation and characterization of nutmeg oil nanoemulsion formula
Nanoemulsions were prepared using a low-energy method (phase inversion concentration). The selected composition was used in a simplex lattice design (SLD). The smallest particle size (105.47 ± 7.90 nm) was observed in run 7 (25% Tween 80, 15% PEG 400). The largest was in run 2 (22.5% Tween 80, 17.5% PEG 400), at 238.34 ± 3.40 nm (Table 5; Figure 2).
Polydispersity index (PdI) values ranged from 0.221 to 0.306, indicating narrow size distributions and good homogeneity (Table 5). Post-centrifugation, an increase in droplet size and PdI was noted, though no physical instability (e.g., creaming or cracking) was observed.

Figure 2. Droplet size distribution in nanoemulsion (N=5) (a), appearance of nutmeg oil nanoemulsion (b).
Table 5. Characteristics of nutmeg oil nanoemulsion based on simplex lattice design method (N=5).
|
Run |
Tween 80 (%) |
PEG 400 (%) |
Physical appearance |
Before centrifugation |
After centrifugation |
||
|
Size (nm) |
Polydispersity index |
Size (nm) |
Polydispersity index |
||||
|
1 |
30 |
10 |
Transparent, yellowish |
187.94 ± 2.28 |
0.288 ± 0.03 |
200.44 ± 2.25 |
0.952 ± 0.02 |
|
2 |
22.5 |
17.5 |
Transparent, yellowish |
238.34 ± 3.40 |
0.227 ± 0.02 |
232.72 ± 54.34 |
0.326 ± 0.03 |
|
3 |
27.5 |
12.5 |
Transparent, yellowish |
222.26 ± 39.00 |
0.306 ± 0.02 |
36.42 ± 0.83 |
0.702 ± 0.04 |
|
4 |
25 |
15 |
Transparent, yellowish |
109.77 ± 18.86 |
0.221 ± 0.02 |
279.74± 108.35 |
0.327 ± 0.07 |
|
5 |
20 |
20 |
Transparent, yellowish |
228.20 ± 0.63 |
0.272 ± 0.01 |
176.86 ± 1.39 |
0.201 ± 0.01 |
|
6 |
20 |
20 |
Transparent, yellowish |
229.94 ± 4.04 |
0.280 ± 0.01 |
127.58 ± 8.68 |
0.319 ± 0.04 |
|
7 |
25 |
15 |
Transparent, yellowish |
105.47 ± 7.90 |
0.274 ± 0.03 |
267.24 ± 60.10 |
0.372 ± 0.03 |
|
8 |
30 |
10 |
Transparent, yellowish |
189.36 ± 1.18 |
0.221 ± 0.01 |
181.5 ± 8.09 |
0.979 ± 0.05 |
Determination of optimum nutmeg oil nanoemulsion formula based on SLD
SLD equations for droplet size and PdI before and after centrifugation are provided in Table 6. Profiling plots are shown in Figure 3a–c. The optimum formulation was predicted to contain 23% Tween 80 and 17% PEG 400, resulting in droplet sizes of 199.846 nm and 264.741 nm (pre- and post-centrifugation), and PdI values of 0.220 and 0.289, respectively (Table 7).
These findings are consistent with recent studies emphasizing the role of systematic experimental design in nanoemulgel development. Optimization using design of experiments (DoE) has been shown to significantly improve droplet characteristics, stability, and therapeutic performance of plant-based nanoemulgels, such as in Melissa officinalis formulations (Koushik et al., 2025).
Table 6. SLD equation for each characteristic parameter of nanoemulsion.
|
Parameter |
SLD equation |
|
Droplet size before centrifugation |
Y = 188.55A + 229.07B – 404.76AB + 22.29AB(A-B) + 2077.49AB (A-B)2 |
|
PdI before centrifugation |
Y = 0.9754 A + 0.2650 B – 0.8987 AB |
|
Droplet size after centrifugation |
Y = 190.97A + 152.21 B + 407.6 AB – 1150 AB(A-B) - 2420AB (A-B)2 |
|
PdI after centrifugation |
Y = 0.9754A + 0.2650B – 0.8987AB |
Note: Y = response of the parameter; A = Tween 80; B = PEG 400
Table 7. Predicted responses of the optimum formulation.
|
Solution |
Tween 80 (%) |
PEG 400 (%) |
a |
b |
c |
d |
|
1 |
23 |
17 |
199.846 |
0.220 |
264.741 |
0.289 |
Note: a = Droplet size (nm); b = Polydispersity index; c = Droplet size after centrifugation stability test (nm); d = Polydispersity index after centrifugation stability test.

Figure 3. Profiling of droplet size and PdI before centrifugation (a), droplet size and PdI after centrifugation (b), and desirability index generated by SLD (c).
Preparation and characterization of the optimum formula of nanoemulsion and nanoemulgel
The optimized nanoemulsion (Table 8) was transparent, yellowish, with 142.66 ± 7.36 nm droplet size and PdI 0.247 ± 0.015. After centrifugation, the droplet size increased to 263.36 ± 5.49 nm. The nanoemulgel, made by dispersing the nanoemulsion in a Carbopol 940 gel base, had increased droplet size (131.98 ± 28.50 nm) and PdI (0.59 ± 0.111), with viscosity 9041.50 ± 278.77 cP and pH 6.0 (Table 8; Figure 4).
Table 8. The characteristic optimum formula of nutmeg oil nanoemulsion and nanoemulgel (N=5).
|
Parameter |
Nanoemulsion |
Nanoemulgel |
|
Physical appearance |
Transparent, yellowish |
Opaque, yellowish |
|
Droplet Size (nm) |
142.66 ± 7.36 |
131.98 ± 28.50 |
|
Polydispersity index (PdI) |
0.247 ± 0.015 |
0.590 ± 0.111 |
|
Droplet size after centrifugation treatment (nm) |
263.36 ± 5.49 |
- |
|
Polydispersity index (PdI) after centrifugation treatment |
0.252 ± 0.010 |
- |
|
Potential zeta (mV) |
-0.10 ± 0.28 |
- |
|
Viscosity (c.Poises) |
- |
9,041.50 ± 278.77 |
|
pH |
- |
6.0 |

Figure 4. Droplet size distribution in nanoemulgel matrix (N=5) (a), appearance of nutmeg oil nanoemulgelax (b).
DISCUSSION
The pseudoternary phase diagram is a tool for optimizing components in an emulsion to obtain the concentration of oil, water, and surfactants that can form a stable emulsion (Jhawat et al., 2021). This study constructed a pseudoternary phase diagram, utilizing various ratios of Smix, water phase, and oil phase, with a total composition of 100%. Smix is constituted of a blend of surfactants and cosurfactants. The use of surfactants alone is insufficient to reduce surface tension (Priya et al., 2015). Therefore, cosurfactants are required to maximize emulsification. The surfactants and cosurfactants utilized in this study were Tween 80 and PEG 400, respectively. Therefore, cosurfactants are required to maximize emulsification efficiency.
Tween 80 and PEG 400 were selected as surfactant and cosurfactant, respectively, based on their complementary hydrophilic–lipophilic balance (HLB) values (15.0 and 11.6). An HLB value >10 is generally considered suitable for oil-in-water nanoemulsions (Chime et al., 2014). Our pseudoternary phase diagram results (Figure 1; Tables 3–4) confirmed that higher Smix ratios improved nanoemulsion stability and minimized droplet size. Specifically, Tween 80:PEG 400 ratios of 2:1 or 3:1 yielded smaller droplets and lower PdI values, reflecting more efficient emulsification. Similar findings were reported in other essential oil nanoemulsions where higher surfactant-to-cosurfactant ratios enhanced droplet stability (Shafiq et al., 2007; Anuradha et al., 2024).
Nanoemulsions were prepared via the low-energy phase inversion concentration method, where gradual addition of water induced system transitions from W/O to LC gel-like, followed by O/W nanoemulsion (Gupta et al., 2016; Gledovic et al., 2020; Chahyani and Zai, 2024). This approach has been widely adopted for essential oil formulations due to its simplicity and ability to preserve thermolabile bioactives (Muñoz et al., 2023).
The organoleptic profile of nutmeg oil nanoemulsion (Figure 2) revealed a golden yellow and transparent system without sedimentation, consistent with previous reports where a transparent appearance indicated nanometric droplet sizes (Narawi et al., 2020; Chahyani and Zai, 2024). The polydispersity index (PdI) is a key parameter for assessing homogeneity; values between 0.221 and 0.306 across our runs indicated narrow particle distribution. Similar PdI values have been reported in coriander oil nanoemulgels (0.188) (Eid et al., 2021) and other essential oil systems (~0.30) (Ullah et al., 2023), supporting the feasibility of achieving narrow distributions. Comparable homogeneity was also described for pectin-stabilized lemon oil nanoemulgels (Muñoz et al., 2023) and argan oil emulgels (Majumder et al., 2023).
Centrifugation-based accelerated stability testing (Wu et al., 2020) confirmed the absence of creaming, flocculation, cracking, or inversion. However, slight increases in droplet size and PdI after centrifugation indicated stress-induced aggregation, a phenomenon also noted in lemon oil–pectin nanoemulgels (Muñoz et al., 2023). Overall, the stability profile observed under accelerated and formulation stress conditions indicates that the developed nanoemulgel possesses sufficient physical robustness for storage, handling, and further development toward large-scale topical applications.
The SLD model (Table 6) further confirmed that increasing PEG 400 elevated droplet size, while balanced Tween 80:PEG 400 ratios reduced particle size and PdI before and after centrifugation. Such interactions between surfactant–cosurfactant blends and droplet stability have been validated in other plant-based nanoemulsions (Hu et al., 2021; Yap et al., 2024).
Optimization using four response criteria (droplet size and PdI before and after centrifugation) identified the best formula with maximum desirability (Figure 3c). The optimized nanoemulsion characteristics (Table 8) aligned closely with experimental validation, underscoring the reliability of SLD prediction.
The nanoemulgel, prepared by incorporating nanoemulsion into Carbopol 940 gel, exhibited increased droplet size and PdI, consistent with reports that gel matrix incorporation may enlarge droplets while enhancing rheology (Hu et al., 2021). Comparable effects were observed in pectin-based lemon oil nanoemulgels (Muñoz et al., 2023) and Piper betle oil formulations (Teo et al., 2024). Despite these increases, droplet size remained within the nanoemulsion range, as indicated by a unimodal distribution (Figure 4a).
Finally, the golden yellowish appearance and nutmeg aroma of the nanoemulgel (Figure 4b) were attributed to nutmeg oil and Tween 80. Similar sensory and stability profiles were reported in other essential oil nanoemulgels (Ahmad et al., 2023; Alam et al., 2024), supporting the reproducibility of organoleptic outcomes across plant-derived formulations.
In addition to laboratory-scale evaluation, the scale-up feasibility of the low-energy nanoemulgel preparation method should be considered. The phase inversion composition (PIC) technique used in this study is advantageous for industrial translation because it requires relatively low energy input, does not depend on high-pressure homogenization, and can be implemented using conventional mixing equipment commonly available in pharmaceutical and cosmeceutical manufacturing. The formulation components used (Tween 80, PEG 400, Carbopol 940, and glycerin) are widely available and commonly applied in topical formulations, supporting regulatory acceptability and production practicality. Nevertheless, scale-up may influence droplet size distribution and rheological behavior due to differences in mixing efficiency and shear conditions. Therefore, further work at pilot scale, including process parameter optimization, batch-to-batch reproducibility, and long-term stability studies, is necessary to ensure consistent product quality during large-scale manufacturing.
CONCLUSION
The optimum nutmeg nanoemulsion formula formed nanoemulsions with good characteristics and stability. The optimum formula also maintained good characteristics of the nanoemulsion after incorporation into the gel base. Moreover, this formulation can be applied to topical natural product development.
AUTHOR CONTRIBUTIONS
Khadijah Zai: Conceptualization (Lead), Methodology (Lead), Formal Analysis (Lead), Validation (Lead), Resource (Equal), Writing – Original Draft (Lead), Writing – Review & Editing (Lead), Investigation (Equal), Supervision (Lead), Project Administration (Equal); Maria Indra Ardriyanto: Data Curation (Lead), Formal Analysis (Equal), Writing – Original Draft (Equal), Writing – Review & Editing (Equal), Investigation (Equal); Annisa Najwa Hanifah: Data Curation (Supporting), Formal Analysis (Equal), Methodology (Supporting), Writing – Review & Editing (Supporting), Investigation (Supporting).
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.
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OPEN access freely available online
Natural and Life Sciences Communications
Chiang Mai University, Thailand. https://cmuj.cmu.ac.th
Khadijah Zai1, *, Maria Indra Ardriyanto2, and Annisa Najwa Hanifah2
1 Department of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
2 Undergraduate Student Program, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
Corresponding author: Khadijah Zai, E-mail: khadijah03@ugm.ac.id
ORCID iD:
Khadijah Zai: https://orcid.org/0000-0003-4447-6177
Maria Indra Ardriyanto: https://orcid.org/0009-0000-9821-0855
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Editor: Sirasit Srinuanpan,
Chiang Mai University, Thailand
Article history:
Received: September 25, 2025;
Revised: February 18, 2026;
Accepted: February 19, 2026;
Online First: March 30, 2026