Indonesian Journal of Pharmacy
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Computational Method to Elucidate Formation and Stabilization Mechanism of Amorphous Solid Dispersion System from Alpha-Mangostin and Poly-Vinylpyrrolidone Using Molecular Dynamics Simulation
The amorphous solid dispersion (ASD) system is a pharmaceutical formulation strategy designed to improve the physical stability and solubility of amorphous drugs. In a previous study, experimental methods suggest that interactions between alpha-mangostin (AM) and poly-vinylpyrrolidone (PVP) can stabilize the amorphous form and maintain the supersaturation levels. Therefore, this study aimed to investigate the formation of the ASD system from alpha-mangostin (AM) and poly-vinylpyrrolidone (PVP) through the computational method. The result of experimental methods showed that the interaction between AM and PVP was confirmed by powder X-ray diffraction, differential scanning calorimetry, and Fourier Transform Infrared Spectroscopy measurement. The hydrogen bonding interactions between AM and PVP were achieved through molecular dynamics (MD) simulation, mimicking the melt-cooling and solvent-evaporation methods. In a direct comparison between the two methods, melt-cooling showed superior attributes, including the lowest binding energy value, as well as reduced root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) values. Nevertheless, ASD was formed by both the melt-cooling and solvent-evaporation methods. Based on the results, the computational method through molecular dynamics simulation provided information on drug-polymer interactions that were difficult to obtain using experimental methods. This method enhanced the current understanding regarding the formation and stabilization mechanism of the ASD system
LC-HRMS Profiling and Antibacterial Activity of Extract and Fraction of Phaleria macrocarpa (Scheff.) Boerl. Fruit
Antibiotics have been found to treat a variety of infectious diseases, which is a crucial health issue. However, the emergence of drug resistance has created new challenges for researchers. Herbal medicine, especially Phaleria macrocarpa (Scheff.) Boerl (as known as Mahkota Dewa plants), can be an alternative antibacterial agent. This study aims to determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of water extracts, ethyl acetate fraction, water fractions, and butanol fractions of peels, fruits, and seed of Phaleria macrocarpa (Scheff.) Boerl. Identification of prediction compounds in the highest antimicrobial activity of the samples are also determined. The extraction method used was infusion with water solvent. Extraction was carried out on the peel, fruit, and seed of Mahkota Dewa. These three water extracts were isolated by a separatory funnel using ethyl acetate and n-butanol solvents. Antimicrobial testing using the broth microdilution method. This assay revealed promising activity against both gram-negative bacteria (Escherichia coli ATCC 8739) and gram-positive bacteria (Staphylococcus aureus ATCC 29213, Staphylococcus epidermidis, and Propionibacterium acnes ATCC 6919). The most active samples as an antibacterial were ethyl acetate fraction of flesh fruits (EAFFF) with MIC value against E. coli, S. aureus, S. epidermidis, and P. acnes were 12.500, 6.250, 3.125, and 12.500 ppm, whereas each MBC values were 12.500, 6.250, 6.250, and 25.000 ppm respectively. Two of the most active fractions were identified by predicting its antibacterial compounds using LC-HRMS. The results showed the presence of 10 predicted compounds in EAFF which had antibacterial properties including 2’, 4’, 3, 4, alpha-pentahydroxy dihydrochalcone 3’-C-xyloside, 5,7,3’4’,5’-pentahydroxy-3,6,8-trimethoxyflavone, p-cymene, taxifolin 3-apioside, eucalyptin, 2-(2’-O-benzoyl)-C-β-D-glucopyranosil-1,3,6,7-tetrahydroxyxanthone, (+)-ar-Turmerone, 2-hydroxy-N’-[(E)-(2-hydroxy-3,5-dinitrophenyl)methylene]-2,2-diphenylacetohydrazide, picroside II, and vitexin 2”-p-hydroxybenzoate while n-butanol fraction of flesh fruit (BFFF) showed 8 predicted antibacterial compounds, 2’, 4’, 3, 4, alpha-pentahydroxy dihydrochalcone 3’-C-xyloside, 5, 7, 3’, 4’, 5’-pentahydroxy-3,6,8-trimethoxyflavone, glycitein, taxifolin 3-apioside, (-)-caryophyllene oxide, α-curcumene, 6,4’-dihydroxyurone 4-O-rutinoside, and α-santonin
Potentially Inappropriate Medications (PIMs) in Geriatric Outpatients Prescriptions in Yogyakarta: Pattern and Factors Related to Occurrences
Potentially Inappropriate Medications (PIMs) were commonly found in geriatric patients’ prescriptions and widely assessed using Beer’s Criteria and STOPP/START tool. In this study we aimed to assess the patterns of PIMs in geriatric outpatients in Yogyakarta, Indonesia and the factors related to the occurrence. This study was using retrospective observational design and conducted at two teaching hospitals in Yogyakarta, Indonesia. The data source included medical records of the outpatients aged 60 years during August to October 2022. The criteria used to evaluate PIMs from the prescriptions were the 2019 AGS Beers® Criteria and STOPP_INA tool based on the STOPP/START version 2 tool. Several predictors, including multimorbidity, polypharmacy, age, gender, health insurance, and working status, were analyzed using a logistic regression model. Out of the 393 subjects included in this study, 193 cases of PIMs were identified in 135 patients (34.35%), with a total of 67 cases according to the Beers Criteria and 141 cases according to STOPP_INA. Aspirin and benzodiazepines were found to be the drugs causing most of PIMs in geriatric patients. Polypharmacy emerged as the strongest predictors of PIM occurrence (p<0.05). The prevalence of PIMs in outpatient geriatric prescriptions at Yogyakarta Hospital was notably influenced by polypharmacy. Therefore, there is a pressing need for vigilant monitoring and meticulous drug selection when prescribing for the elderly population to mitigate the potential risks associated with PIMs
Moringa Oleifera Lam Leaves Extract and Its Compounds Effect on The Intracellular Calcium Release in Human Aortic Smooth Muscle Cells
Moringa oleifera leaves have been scientifically shown lower blood pressure but the mechanism of action on this is achieved has not been fully explored. Intracellular calcium release is a fundamental cellular process linked to vascular function and modulation of this process can have significant implications for cardiovascular health. The blocking effects of calcium influx and release by Moringa oleifera Lam leaf extract and its compounds on the human aortic smooth muscle cells (HAoSMCs) were studied. The cell viability assay was carried out to determine the concentrations of M. oleifera Lam leaf extract and its compounds for the assay. Test compounds (amlodipine, chlorogenic acid, gallic acid, kaempferol, M. oleifera leaf extract, quercetin and vicenin-2) were incubated with Quin-2-AM in the presence and absence of extracellular calcium (Ca2+) and with the addition of caffeine and potassium (K+) in HAoSMCs. Following treatments with the test compounds, the influx of extracellular Ca2+ into the cytosol of HAoSMCs was significantly inhibited (p <0.001). The test compounds significantly (p <0.001) decreased the concentration of cytosolic Ca2+ induced by K+ depolarisation. The test compounds also significantly (p <0.001) affected the intracellular Ca2+metabolism, regulated by the caffeine-sensitive storage site in HAoSMCs. No synergistic effect on the decreasing of cytosolic Ca2+ level was observed when the test compounds were used in combination with amlodipine. M. oleifera Lam leaf extract and its compounds may act as Ca2+channel blockers (CCBs) and there is also a possibility of interactions between the test compounds and amlodipine
Health Technology Assessment Practice in Indonesia: A comprehensive study of Fibrinolytic Therapy among ST-Segment Elevation Myocardial Infarction Patients
Acute coronary syndrome disease is responsible for half of all cardiovascular disease-related deaths and encompasses all ischemic symptoms, including ST segment elevation myocardial infarction. Streptokinase and alteplase each have advantages and disadvantages, both in terms of the economic, safety, and efficacy aspects that need to be considered in their use for STEMI patients. The aim of this study was to compare the effectiveness of using alteplase and streptokinase among STEMI patients in Indonesia. This study uses a retrospective cohort method and a systematic review to evaluate clinical effectiveness, makes a decision tree analysis model for economic evaluation, analyzes the cost impact, and uses qualitative analysis to determine clinical preferences. The proportion of patients with stable CAD in the Alteplase group was greater than in the Streptokinase group (87.37% vs. 62.50%). Based on this proportion, Alteplase is considered to be able to significantly reduce the incidence of MACE in STEMI patients compared to patients receiving Streptokinase therapy (RR 1.398; 95% CI 1.058–1.848). The decision tree model showed that the incremental cost-effectiveness ratio (ICER) value of the use of Alteplase when compared with Streptokinase produced in this study was 24.27 million rupiahs per stable CAD patient. The qualitative data revealed there was no significant difference in the use of Alteplase or Streptokinase except for the time required for monitoring. The clinical effectiveness of Alteplase is consistently better than Streptokinase for the management of STEMI patients. The cost-effectiveness analysis shows that although Alteplase costs more than Streptokinase, its use provides greater clinical benefits. The budget requirement for the provision of Alteplase as the main therapy for STEMI patients in Indonesia is IDR 272.15 billion in 2025. In the context of selecting a fibrinolytic agent, cardiologists and vascular specialists are more likely to use Alteplase
Potential drug interaction of corticosteroids and symptomatic therapy in COVID-19 patients in RSUD Banyumas, Indonesia
Corticosteroids may interact with another drug used in COVID-19 treatment. Drug-drug interactions can diminish the efficacy of drugs in the body, necessitating proper management. This study aimed to identify potential drug interactions in COVID-19 therapy at Banyumas Hospital, Indonesia. This study implemented descriptive observational methodology with a retrospective design. The study included all COVID-19 inpatients at the Banyumas Hospital between June 2020 and June 2021. Potential drug interactions were analyzed using the Drugs Interaction Checker on Drugs.com and Lexicomp on UpToDate. Among 334 patients, pharmacokinetics (189 cases, 38.10%), pharmacodynamics (264 cases, 53.23%), and unknown (44 cases, 8.87%) drug interaction may occur. Based on the severity, the potential for drug interactions were classified as significant (50 cases, 10.08%), moderate (204 cases, 41.13%), and minor (243 cases, 48.1%). Patients with COVID-19 are at risk for potential drug interactions, most of which cannot be avoided. It is important to select appropriate drug uses and manage therapy appropriately to reduce the incidence of potential drug interactions.
 
Cost of COVID-19 Mass Vaccination at Ngampilan Health Center Yogyakarta
The Corona Virus Disease-19 (COVID-19) outbreak had a significant impact on every sector. To minimize the case and the mortality rate, the vaccination program is accelerated using every possible strategy. One of the strategies employed in Indonesia is the mass vaccination program. This study aimed to estimate the unit cost of the mass vaccination program service delivery of COVID-19 Sinovac vaccine per dose and per fully vaccinated (2-dose) against COVID-19 in a public health center facility in Yogyakarta city. The costing study used activity-based cost according to the financial data, interviews, and direct observations. The incremental financial cost and full economic cost were calculated using the government or provider's point of view. The total cost is then divided by the number of doses injected and multiplied by two to get the cost per fully vaccinated person. The incremental financial cost and economic values per dose were USD32.64 and USD33.57, while for the fully vaccinated person (2-dose) using Sinovac Vaccine were USD 65.28 and USD 67.15, respectively. Based on the one-way sensitivity analysis, the unit cost per fully vaccinated is influenced by vaccine price and the number of vaccinated people per mass vaccination session
The Use of DLBS3233 Bioactive Fraction in Type 2 Diabetes Mellitus Management in Indonesia: A Cost-Effectiveness Analysis of Real-World Evidence
Diabetes has a significant clinical and economic impact to the society. Inlacin (DLBS3233 bioactive fraction) is a phytopharmaceutical for diabetic patients that can be used as an additional therapy for maintenance purposes. Therefore, Cost-Effectiveness Analysis (CEA) for Inlacin needs to be done to provide an overview of its potential. Aims of this study was to define the cost-effectiveness of phytopharmaceuticals on type 2 diabetes mellitus management in Indonesia. This study was performed using societal perspectives with observational-based cost-effectiveness analysis.The clinical and economic data were retrospectively collected (2007-2022) from a total of 137 participants, of whom 66 were Inlacin Group and 71 were Non-Inlacin Group. The clinical data consisted of HbA1c level, effectiveness, utility, and Visual Analogue Score (VAS), while the economic data consisted of Direct Medical Cost, Direct non-Medical Cost, and Indirect Cost. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) gained was estimated to determine the cost-effectiveness. Deterministic sensitivity analysis was conducted to assess the impact of parameter uncertainty. In the base case, inlacin provided a more economic and more effective treatment than non-inlacin with a total cost of IDR 6,837,195 (USD 434.42 ) vs IDR 7,870,056 (USD 5004.17) and a total QALYs of 0.490 vs 0.464. The ICER of IDR 39,535,349 (USD 25,259.62 ) is considered cost effective according to the willingness to pay threshold (2021 3x Indonesian GDP is Rp.201,504,163 = USD 12,813.45). The most influential drivers of cost-effectiveness in deterministic sensitivity analysis were the changes of the total cost of Inlacin, the price of medicine on non-Inlacin group, and the direct medical cost of non-Inlacin group. Based on the current price in Indonesia, inlacin can be considered a cost-effective option, although this depends heavily on the willingness to pay threshold. Further Markov Modeling studies with inlacin are needed to inform the decision-making process
An Emerging of Essential Oils with Antifungal Activities as Anti-dandruff in Formulation
Dandruff could be an exceedingly disturbing scalp condition to most people. It has various causes, from fungus, bacteria, scalp irritation due to excessive sun exposure or even excessive shampoo exposure. As the world of beauty moves towards natural cosmetics, alternative anti-dandruff agents that use essential oils are quite popular these days. Essential oils such as tea tree, lemongrass, and lavender can act as antimicrobial agents against the causes of dandruff. This review describes the anti-dandruff potential of various essential oils on several dandruff-causing microorganisms such as Malassezia furfur and Candida albicans. The review method includes comparative research methods from research journal sources obtained from the internet, covering articles from 2013 to 2022, with topics that focused on essential oils with anti-dandruff and antifungal activity. The results of this review indicate that various essential oils, especially those highlighted in this article, show strong potential to inhibit the growth of dandruff-causing microorganisms and may be developed into stable anti-dandruff formulations
Antimicrobial Prospects of Domesticated Ornamental Leaf Extracts Against Skin Pathogens
The increasing popularity of natural plant-based treatments offers an alternative to conventional therapies for various cutaneous infections due to their potential efficacy and lower side effects. Thus, the present study aimed to investigate the antimicrobial and cytotoxic properties of leaf extracts from five selected domesticated ornamental plants against pathogens implicated in acne vulgaris and dermatophytosis. The selected plant leaves were successively macerated with solvents of increasing polarity and the extracts were underwent qualitative phytochemical analysis. The antimicrobial activities were evaluated using the broth microdilution method. Extracts with high antimicrobial activity (MIC≤128µg/mL) were subsequently tested for cytotoxicity on BJ fibroblast cells, and the selectivity index (SI) was calculated. Extraction yields were highest in Bougainvilea glabra (72.04%) and lowest in Plumeria obtusa (21.6%). Phytochemical screening revealed the presence of alkaloids, flavonoids, terpenoids, tannins, phenols, quinolones, saponins, and coumarins, with phenols found in all extracts. The aqueous extract of Alamanda cathartica (AC-Aq) and the methanol extract of Ixora coccinea (IC-Met) showed the most potent antibacterial activities against P. acnes and S. epidermidis, with MIC values of 128μg/mL and 64μg/mL, respectively. Antifungal activity was most pronounced in AC-Aq against T. mentagrophytes and T. rubrum, with MIC values of 32μg/mL. The six active extracts revealed varying degrees of toxicity, with the aqueous extract of P. obtusa (PO-Aq) exhibited the least cytotoxicity (CC50: 713.31±3.71 μg/mL), while IC-Aq was the most cytotoxic (CC50: 116.72±2.28 μg/mL). AC-Aq demonstrated the highest SI values, indicating effective antimicrobial activity at non-toxic concentrations