JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA

Optimization Using D-Optimal Design of Nanostructured Lipid Carrier (NLC) with Variation of Surfactants and Co-surfactant

Wafa'ul Athiyyah — 2025-04-16

Background: Nanostructured lipid carriers (NLC) are topical delivery systems designed to address the challenges associated with active ingredients, such as poor solubility and limited skin penetration. NLCs incorporate surfactants, such as sorbitan monooleate and lauryl glucoside, to stabilize the system, while the addition of soy lecithin as a co-surfactant further enhances NLC stability. A D-optimal design was employed to optimize the NLC components, ensuring that the formulation achieved the desired characteristics. Objective: To determine the optimal NLC formulation. Method: Optimization was conducted using the D-optimal design method. The NLCs were prepared using the high-shear homogenization method with an Ultra-Turrax device. Characterization included measuring the particle size, polydispersity index (PDI), pH, and creaming index. Results: All formulations resulted in homogeneous emulsions with a white color, slight aroma of castor oil, smooth texture, and thick consistency. The particle sizes ranged from 200 to 500 nm, although the polydispersity index was not significantly influenced by surfactants or co-surfactants. All the formulations maintained an appropriate pH range for skin compatibility and product stability. The %creaming index demonstrated that the co-surfactant effectively reduced creaming in the NLCs. Conclusion: The optimal formulation consisted of 0.284% sorbitan monooleate, 3.429% lauryl glucoside, and 0.287% soy lecithin.

Design and Optimization of Nanostructured Lipid Carriers for Quercetin in Skin Lightening Applications

Ressa Marisa — 2025-04-16

Background: Quercetin, a potential skin-lightening agent, reduces intracellular and fungal tyrosinase activities. However, its poor water solubility and limited skin permeability hinder its applications. Nanostructured lipid carriers (NLCs), which are composed of biocompatible and biodegradable lipids, enhance drug stability and skin penetration. The lipid type, surfactant concentration, and formulation parameters influence NLC stability. Objective: This study aimed to optimize NLC formulations for quercetin delivery by evaluating their organoleptic properties, particle size, polydispersity index (PDI), and pH. Methods: NLCs were prepared using 10% total lipids (4% solid and 6% liquid lipids) and surfactant mixtures at varying concentrations via High Shear Homogenization. Initial formulations using myristic acid and castor oil were unstable and underwent phase separation within five days. Results: Substituting the solid lipid with a 1:3 combination of beeswax and cocoa butter produced a stable formulation during storage at room temperature. The lipid and surfactant compositions significantly influenced the particle size and PDI. While the pH remained stable, statistical analysis revealed significant changes in particle size and PDI across the formulations. Conclusion: Optimized NLC formulations for quercetin delivery demonstrated improved stability and potential for effective skin lightening. Further research is warranted to evaluate the in vivo efficacy and scalability of this approach.

Curcuma caesia. Roxb as a Potential Inhibitor of STAT3 and EGFR: a Molecular Docking Approach in Diabetic Nephropathy

Muhammad Farid — 2025-04-16

Background: Diabetes mellitus (DM) is a chronic disorder marked by persistent hyperglycemia, leading to various complications, including diabetic nephropathy (DN). The STAT3-EGFR signaling axis plays a crucial role in the development and progression of diabetic nephropathy, with EGFR activation leading to STAT3 phosphorylation. Curcuma caesia Roxb, rich in curcuminoids, shows promise in managing DN due to its anti-inflammatory and antioxidant properties. This study aims to predict the inhibitory potential of Curcuma caesia compounds on STAT3 and EGFR in DN using molecular docking techniques. Methods: This study utilized molecular docking to evaluate the inhibitory potential of Curcuma caesia compounds on STAT3 and EGFR. Protein structures were obtained from the RCSB database and prepared using Biovia Discovery Studio. Redocking validated the method via RMSD analysis, while docking simulations assessed binding energy (ΔG). ADMET predictions analyzed physicochemical properties and toxicity, ensuring the compounds' suitability as drug candidates. Results: Redocking process validated the method, with RMSD values indicating accuracy. Curcumin (-9.71) and ar-Curcumene (-5.02) showed the lowest binding energy for both proteins, suggesting strong interactions. Visualization revealed significant amino acid interactions, particularly involving hydrogen bonds. Additionally, pharmacokinetic and toxicity analyses indicated that most compounds are suitable drug candidates, exhibiting good absorption, distribution, and safety profiles, thus supporting Curcuma caesia's therapeutic promise in diabetic nephropathy management. Conclusion: Curcuma caesia demonstrates significant potential as a therapeutic agent for diabetic nephropathy, with favorable molecular interactions, strong binding affinity to STAT3 and EGFR, and promising pharmacokinetic and safety profiles.

Potassium Profile in Heart Failure Patients Before and After Hospitalization at Prof. Dr. I.G.N.G. Ngoerah Hospital

Kadek Indra Aryani — 2025-04-16

Background: Hypokalemia in patients with heart failure is increasing, with an increasing incidence of 6.8% in Asia and 19.7% in Indonesia; globally, 63 million people suffer from heart failure. Hypokalemia is defined as a serum potassium level below 3.5 mEq/L [mmol/L], which can lead to decreased heart function, muscle weakness, arrhythmias and cardiac arrest. The use of diuretic drugs such as furosemide in heart failure patients may be a risk factor for hypokalemia. Objective: This study aims to determine the difference in potassium levels before and after furosemide administration as well as the possibility of hypokalemia due to furosemide administration in inpatients diagnosed with heart failure at Prof. Dr. I.G.N.G. Ngoerah Hospital. Methods: This is a cross-sectional observational study with retrospective medical record collection. The minimum sample size was calculated using Lemeshow's Formula of One Proportion Estimation Method with Absolute Precision Proportion, data normality test with Kolmogorov-Smirnov (p>0.05) and parametric test with paired t-test (p<0.05). This study included 101 patients that met the inclusion criteria with 11 patients having more than one inpatient visit, so a total 114 'patients' medical records were obtained. Results: Potassium levels before and after hospitalization showed a significant difference (p<0.05). A total of 84 'patients' data showed a decrease in potassium levels, with 49 of them showing a reduction in >15% and 35 showing a decrease of ≤15%. Conclusion: Prevalence of hypokalemia in patients with a diagnosis of heart failure and furosemide therapy at Prof. Dr. I.G.N.G. Ngoerah Hospital during January 2022-December 2023 after hospitalization was 29%.

Antiinflammatory Activity of Bangle Rhizome (Zingiber purpureum Roxb) Ethanol Extract on Rat Carrageenan Induced and Erythema Method

Mia Ariasti — 2025-04-30

Background: Inflammation is a physiological response triggered by cellular damage, typically characterized by symptoms such as edema. Objective: This study was conducted to evaluate the anti-inflammatory activity of the ethanol extract of Bangle rhizome (Zingiber purpureum Roxb.) using the carrageenan-induced paw edema method and the UVB-induced erythema method. The most effective dose demonstrating significant anti-inflammatory activity was also determined. Methods: The bangle rhizome (Zingiber purpureum Roxb) was subjected to maceration using 96% ethanol. A total of 25 rats were randomly divided into five groups: negative control (0.5% CMC-Na), positive control (diclofenac sodium at 0.9 mg/200 g body weight), and treatment groups receiving ethanol extract of bangle rhizome at doses of 5, 10, and 20 mg/200 g body weight. In the carrageenan-induced method, the edema volume in the rat paw was measured following the administration of 0.8% lambda-carrageenan. In the erythema method, the degree of inflammation was assessed using UVB-induced erythema scoring. Results and Conclusion: Anti-inflammatory activity was observed at doses of 5, 10, and 20 mg/200 g body weight in the carrageenan model and at doses of 10 and 20 mg/200 g in the erythema model. The most potent anti-inflammatory effect was recorded at the dose of 20 mg/200 g body weight, which was comparable to the positive control in both models. The presence of flavonoids and steroids in the extract may contribute to the observed anti-inflammatory activity.

Assessment of Geriatrics Patients with Cardiovascular Disease Prescriptions for Appropriateness of Medications by Using Beers Criteria in Muhammadiyah Lamongan Hospital

Dyah Puspita Sari — 2025-04-30

Background: Number of geriatric residents has increased annually. Owing to pathological and physiological conditions, the geriatric population tends to consume more medications, thereby increasing their risk of adverse side effects and drug interactions. Objective: This study was to evaluate the appropriateness of therapy for outpatient geriatric patients with cardiovascular disease at Muhammadiyah Lamongan Hospital from August to October 2023. Methods: American Geriatrics Society (AGS) Beers Criteria are one of the tools used to identify drugs whose potential harm outweighs the expected benefits and should be avoided in the elderly population. This study employed a descriptive method, with retrospective data collection from secondary sources, including medical records and electronic prescriptions. Results: Findings revealed that out of 252 prescriptions for geriatric patients with cardiovascular disease, four types of medications were potentially inappropriate according to the Beers Criteria: nifedipine with 23 prescriptions (9.13%), amiodarone with one prescription (0.40%), digoxin with 13 prescriptions (5.16%), and diltiazem with four prescriptions (1.59%). Conversely, three types of medications were deemed appropriate: aspirin (96 prescriptions, 38.10%), digoxin (30 prescriptions, 11.90%), and diltiazem (11 prescriptions, 4.37%). In conclusion, of the 252 prescriptions reviewed for geriatric patients with cardiovascular disease, three types of drugs are appropriate, while four types increase the risk of potentially inappropriate treatment (PIM) based on the Beers Criteria. Conclusion: These findings underscore the need for careful consideration to mitigate the risk of drug reactions. If the medication cannot be used in geriatric patients, an alternative therapy should be used or a dose adjustment may be necessary.

Antihypertensive Activity of Black Garlic Extract in Rats and Its Phytochemical Analysis using GC-MS

Daru Estiningsih — 2025-04-30

Background: Hypertension is defined as a medical condition where blood pressure rises above 140/90 mmHg. Black garlic is recognized as a natural remedy that may help lower high blood pressure, primarily due to its abundant antioxidant properties, which are believed to inhibit the function of the angiotensin-converting enzyme (ACE) that is essential for regulating blood pressure. Objective: This study aimed to identify the chemical composition of black garlic using GC-MS and assess its antihypertensive effects in rat models. Methods: This study characterized the chemical composition of black garlic using GC-MS (Agilent 7890A) and evaluated its antihypertensive effects in rats. Hypertension was induced by oral administration of NaCl at a dose of 3.75 g/20 g body weight (BW) from day 0 to day 14. Blood pressure measurements were taken on days 0, 14, and 21. Black garlic extract was administered at three dose levels 4.2 mg/20 g BW, 8.4 mg/20 g BW, and 12.4 mg/20 g BW to evaluate dose dependent antihypertensive responses. Statistical analysis included the Kolmogorov-Smirnov test for normality, homogeneity testing, One-Way ANOVA Results: The GC-MS analysis identified 9-octadecenoic acid as the dominant compound in black garlic, accounting for 34.53% of its total composition. The antihypertensive activity test showed that administering black garlic at a dose of 12.4 mg/20 g BW significantly lowered systolic, diastolic, and mean arterial blood pressure while enhancing nitric oxide levels in hypertensive rats. Conclusion: Black garlic has the potential as an effective herbal treatment to lower blood pressure.

Formulation and Physical Evaluation of Kratom (Mitragyna speciosa Korth.) Leaf Extract Emulgel as Analgesic in Mice (Mus musculus)

Iqmal Zulhakim — 2025-04-30

Background: Kratom leaves contain major alkaloid compounds, particularly mitragynine and 7-hydroxymitragynine which have demonstrated anti-pain or analgesic properties. Objective: This study aims to evaluate the effectiveness of kratom leaf extract emulgel in reducing pain when applied topically in mice. Methods: This study was conducted on male mice that had been induced with acetan acid intraperitoneally. Following induction, emulgel formulations were applied topically and pain responses were recorded every five minutes over 30 minutes period. Group 1 (emulgel base without active ingredient), Group 2 (voltaren emulgel), Group 3 (emulgel with 5.6% extract concentration), Group 4 (emulgel with 11.6% extract concentration) and Group 5 (emulgel with 17.6% extract concentration). Results: The results of physical evaluations of emulgel formulations met the applicable standards. Observations of pain responses indicated optimal analgesic effect in the emulgels containing 11.6% and 17.6% extract concentration with analgesic values of 51.52% and 63.06% respectively. An active substance is considered to have analgesic activity whent it demonstrates ≥50% effectiveness. Conclusion: This study concluded that emulgels formulated with kratom leaf extract exhibited analgesic activity as evidenced by the decreased in the writhing response of mice every five minutes.

In Vitro Evaluation of Antidiabetic and Anti-Inflammatory Activities of Five Selected Syzygium Leaves Ethanolic Extract as Alpha-Glucosidase Inhibitors and Anti-denaturation of Bovine Serum Albumin (BSA)

Meiliza Ekayanti — 2025-04-30

Background: Diabetes mellitus (DM) has become a major health problem worldwide, with a continuous increase in mortality due to complications caused by hyperglycemia. Chronic hyperglycemia is often associated with inflammation due to increased production of free radicals. Objective: This study’s main objective is to assess antidiabetic and anti-inflammatory properties in vitro of five particular Syzygium leaves extract (S. cumini, S.aqueum, S. malaccense, S. polyanthum, and S. aromaticum) using alpha-glucosidase and Bovine Serum Albumin (BSA). Methods: The five of selected Szygium leaves were macerated by using ethanol 96%, each extract was assessed in vitro for antidiabetic activity by analyzing the inhibitory of alpha-glucosidase using acarbose as strandard, and anti-inflammatory activity by analyzing the inhibitory denaturation of BSA Heat-induced and BSA induced by 2,2-diphenyl-1-picrylhydrazine (DPPH) with Sodium diclofenac as standard. Results: The IC₅₀ of α-glucosidase inhibition was 76.235 µg/mL (strong) for S. malaccense and 0.241 µg/mL (very strong) for the acarbose standard. The greater IC₅₀of antidenaturation of BSA with heat-induced was S. polyanthum (95.7 µg/mL) and sodium diclofenac standard (59.25 µg/mL) both were strong inhibitor. Along with greater anti-denaturation of BSA, DPPH-induced S. malaccense (90.320 µg/mL) and sodium diclofenac standard (43.301 µg/mL), both of which are strong inhibitors. Conclusion: The ethanol extract of Syzygium leaves has the potential to be developed as an antidiabetic and anti-inflammatory herbal medicine, particularly S. malaccense and S. polyanthum leaf extracts, which provided greater activity in this study.

In Silico Study of Green Tea (Camellia sinensis) Compound as Potential Anxiolytic Drug Material Targeting Estrogen Alpha Receptor

Harfiah Nur Aini — 2025-04-30

Background: The prevalence of anxiety disorders has significantly increased each year but has not been matched by the availability of adequate treatments. Estrogen receptor alpha (ERα) is known to induce anxiety through the activation of a complex system in the body, and drugs that inhibit ERα activity are predicted to have anxiolytic potential. Objective: This study aims to evaluate 50 compounds derived from green tea leaves to discover potential anxiolytic candidates that act by inhibiting ERα. Methods: The research methods used include toxicity screening, pharmacokinetic screening, drug scan, molecular docking, and molecular dynamics. Results: Based on the screening results, quercetin was identified as non-carcinogenic, non-hepatotoxic, easily absorbed, evenly distributed, non-interfering with CYP2D6 enzyme metabolism, and potentially effective as an oral drug. In molecular docking results, quercetin showed a ΔG value of -7.54 kcal/mol and Ki of 2.97 µM, which are better than the reference drug with a ΔG value of -7.20 kcal/mol and Ki of 5.24 µM. Quercetin also shown more stable interactions with the Erα binding site, indicated by amino acids Glu353 and Arg394 in RMSD and RMSF analysis during molecular dynamics simulation. Conclusion: From the study result it can be concluded that quercetin has potential as a good candidate for anxiolytic drug material by inhibiting ERα activity.

Influence of Hesperetin Concentration in Poloxamer P84 and TPGS Mixed Micelles on Physical Characteristics and Cytotoxicity in T47D Cell Line

Nanda Intan Aulia — 2025-04-30

Background: Hesperetin is a natural compound that has several properties including anticancer, but has limitation on low solubility in water. In this case, the development of a hesperetin delivery system using the micellar system is carried out. Objective: The current study aims to determine the effect of drug concentration on the physical characteristics and cytotoxicity of the mixed micelle. Methods: In this study, mixed micelles were formulated with D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poloxamer P84 as polymers through the thin film method, with hesperetin loaded at four different concentrations, i.e., 5 mg (F1), 10 mg (F2), 20 mg (F3), and 40 mg (F4). The mixed micelles were formulated using thin film hydration method. The evaluation of micelle’s physical characteristics was the measurement of particle size, Critical Micelle Concentration (CMC) value, drug loading, and drug entrapment efficiency. The evaluation of cytotoxicity used the T47D cell line and Micro Tetrazolium (MTT) method. Results: The CMC value of the mixed micelle was 0.0029% w/v, which was lower than the CMC of TPGS and poloxamer P84 only. The particle size of the micelles produced was between 17.07–20.37 nm. Among the various formulations, F3 showed relatively small particle size and has homogeneous particle size, high drug loading and encapsulation efficiency, and low IC₅₀. Based on the study, particle size of F3 was 17.93 0.32 nm with polydispersity index (PDI) of 0.256 0.034. The drug loading percentage of F3 was 4.0092 0.0048% with an encapsulation efficiency of 94.5492 0.0013%. Based on cytotoxicity test using MTT method, F3 has low IC₅₀, there was 4.036 ppm. Conclusion: Hesperetin-loaded mixed micelles offer potential as anticancer drugs that improve hesperetin efficacy. The results showed that F3 was the most potent anticancer formulation based on the physical characteristics and cytotoxicity tests.

Formulation, Characterization, and In Vitro Evaluation of Sunscreen Cream Containing Kenikir (Cosmos caudatus Kunth.) Extract and Chicken Bone Collagen Hydrolysate

Annisa Zukhruf — 2025-04-30

Background: Sunlight is a major contributor to skin damage, including erythema, pigmentation, premature aging, and other related conditions. Kenikir extract contains flavonoid derivatives, which have the potential to act as sunscreen due to the presence of chromophore groups that can reduce the intensity of sun exposure on the skin. In this study, sunscreen was made from kenikir extract with the addition of collagen hydrolysate. Objective: This study aims to assess the effectiveness and characteristics of various sunscreen cream formulations produced. Methods: Kenikir extract was obtained through ethanol-based maceration, while collagen hydrolysate was prepared by isolating chicken bone collagen using acetic acid solvent, followed by enzymatic hydrolysis with bromelain. Four sunscreen cream formulations were developed using various concentrations of kenikir extract and collagen hydrolysate. The creams were characterized by evaluating sun protection factor (SPF), percent erythema, percent pigmentation, organoleptic properties, acceptance testing, homogeneity, pH, viscosity, centrifugation, and spreadability. Results: The cream containing kenikir extract was effective as sunscreen with an SPF of 45.59, erythema of 1.96%, and pigmentation of 1.27%. It also exhibited homogeneity, with a pH of 7.83 and a viscosity of 46,700 cps, which met the permissible range for sunscreen use. The stability test indicated that it was stable, with no separation observed. Conclusion: Sunscreen cream containing kenikir extract has the potential to protect the skin from excessive sun exposure due to the effectiveness and good characteristics according to the Indonesian National Standard (SNI).

Formulation of Lip Balm Extract of Temu Mangga Rhizome (Curcuma mangga Val) as Moisturizer

Rina Andriani — 2025-04-30

Background: Lip balm moisturizes the lips and can be made from natural ingredients such as mango rhizome extract (Curcuma mangga Val), which is rich in antioxidants. Objective: This study aims to evaluate the formulation of lip balm with varying concentrations of mango rhizome extract and determine its optimal concentration. Methods: The research employs a qualitative and quantitative approach using 1 Kg of mango rhizome simplisia from Southeast Sulawesi. The lip balm formulations include extract concentrations of 0%, 5%, 10%, and 15%, involving ingredients such as mango rhizome extract, cera alba, olive oil, glycerin, BHT, nipasol, strawberry essence, D & C Red 6, and vaseline album. Evaluation was conducted through organoleptic tests, pH, homogeneity, adhesion, spreadability, melting point, cycling test, moisture, irritation, and panelist preference. All formulations demonstrated stability in color, texture, and aroma at room temperature and during the cycling test. Consistency, homogeneity, and pH of all formulas remained stable. Results: Spreadability and adhesion improved with the concentration of the extract, with Formula F3 (15% extract) showing the best results, including an increased melting point indicating thermal stability. All formulas were safe and did not cause irritation. Preference tests indicated that F3 was preferred for moisture, while F1 and F2 were favored for aroma and color. Conclusion: The mango rhizome extract lip balm is stable, safe, and effective as a lip moisturizer, with Formula F3 being the most effective. Future research is expected to develop other formulations from mango rhizome to enhance moisturizing effects while maintaining the stability of the preparation.