Indonesian Journal of Pharmacy
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Microencapsulation of Ethyl Acetate Extract from Green Coffee Beans (Coffea Canephora) by Spray Drying Method
Coffee contains caffeine and chlorogenic acid (CGA) as the main constituent benefiting human health. Extract of green coffee beans (GCB) has some limitations in terms of its unpleasant flavour, aroma, and phytoconstituents bioactivity. This study aimed to encapsulate the crude ethyl acetate (EtOAc) extracts of Gayo Robusta GCB (Coffea canephora) to overcome its limitation. Microencapsulation was carried out by spray drying method using whey protein concentrate (WPC) as a coating material to produce nutraceutical supplement microparticles. The microparticles size, morphology, and physicochemical characteristics were investigated. We found that the yield of microparticles was 39.5%, volume diameter was1.367 µm, and span was 1.162 µm. The morphology of the microparticles was irregular microspheres particle with dense, smoothness, wrinkle, shrivel, compactness, and homogeneous structure shape particles. The physicochemical properties measurentment indicated that it has scavenging radical activity value (RSA) 374.53 µg/mL, total phenol content (TPC) 6.92 g GAE/kg, caffeine content 9.12%, and CGA levels 7.19%. The spray drying microencapsulation by using WPC was able to engulf and package the unpleasant flavour and aroma of the crude extract of Gayo Robusta GCB, produce abundant yield of smaller and narrower particle, and protect and carry considerable amounts of phytoconstituents bioactivity.
 
Application of Box Behnken Design and Response Surface Methodology for Optimization Sonication Conditions of Nanostructured Lipid Carrier from Mixtures of Palm Stearin and Palm Olein
The study aimed to determine the optimum conditions of the sonication in the manufacture of nanostructured lipid carriers (NLC). Nanostructured lipid carriers were developed using a mixture of palm stearin and palm olein, water, and tween as surfactants. Optimization was carried out to obtain nanostructured lipid carriers with a size below 200nm, zeta potential + 30 mV, and polydispersity index below 0.5. Optimization of NLC using response surface methodology and Box-Behnken experimental design. The independent variables were amplitude (A, kHz), pulse on pulse off (B, minute), and time of sonication (C, minute) each at three levels, while dependent variables were zeta potential (Y1, mV), particle size (Y2, nm), and polydispersity index (Y3). Measurement for dependent variables using the Zetasizer Nano ZS particle size analyzer utilized with Malvern software (Malvern, UK). The optimum formulation was obtained at a combination of amplitude (35 kHz), pulse on pulse off (pulse on 9 pulses off 3), and time of sonication (3 minutes 25 seconds ). This resulted in NLC having particle size 127.9 nm, polydispersity index 0.191, the zeta potential of -27.3 mV
Expression, Microencapsulation of Recombinant Human Epidermal Growth Factor, and Release Study in Gastric Ulcer Representing Condition
Recombinant human epidermal growth factor (rhEGF) has been studied and expressed in various expression systems. It has been also commercialized and clinically used, yet limited to topical diseases. However, being naturally expressed in different tissues, the rhEGF is potential to be applied not only for external wound and skin disorders, but also to regenerates internal damaged epidermal cells such found in gastric ulcer. In the recent study, chitosan microparticles were developed to facilitate delivery of the rhEGF and to overcome gastric degradation that majorly interfere protein, particularly rhEGF oral administration. The rhEGF was expressed in E. coli BL21(DE3) and purified using Ni-NTA chromatography. The refolded rhEGF showed proliferation activity on MC7 cells. rhEGF loaded chitosan microparticles were stable in the gastric and specifically released the loaded rhEGF in the high oxidative environment in acidic pH representing gastric ulcer condition.
 
A Novel Stability Study of Simvastatin Generic Tablet in Public Pharmacy Facilities of Purwakarta District, Indonesia
Drug stability is one of the most important criteria for producing safe, excellent and effective products. Some environmental factors that influence drug stability are light, temperature, and humidity. Simvastatin is a cholesterol-lowering drug that is known to be sensitive to high temperature and humidity. The purpose of this study is to analyze the effect of 6 months of real-time storage conditions on the stability of generic simvastatin tablets in public pharmacy facilities. This study used simulation method with 4 brands of simvastatin generic tablets with two different strengths (10 mg and 20 mg). In the process, the sample was conditioned in 6 different regions for 6 months. The results of temperature and humidity monitoring showed 2 locations at ≤ 25 ° C, 4 locations had a temperature of ≥ 25 °C and all locations had humidity > 65 %. The drug was evaluated for physical and chemical quality parameters at months 0, 3, and 6. After being stored for 6 months, the tablets showed a decrease in disintegration time and an increase in the friability, showing lack of durability. Similarly, there was a decrease in the content concentration in the tablets but fortunately the level was still within the accepted specification range (90 – 110 %). However, there was one tablet that did not meet the dissolution test requirements after the storage duration (Q ≤ 75 % at 30 minutes). The results of the stress test showed that simvastatin degraded in all conditions. This stress test confirmed the extreme instability of simvastatin. Poor storage conditions can reduce the quality of generic simvastatin tablets, thus a well-controlled environment is vital in pharmacy facilities
Integrative Bioinformatics Analysis Reveals Possible Target and Mechanism of Ellipticine Against Breast Cancer Stem Cells.
Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), an alkaloid isolated from plants Ochrosia elliptica, showed anticancer activity. A previous study demonstrated that ellipticine exhibited a reduction of the proliferation and self-renewal ability of ALDH1A1-positive breast cancer stem cells; however, the mechanisms have not been fully clarified. In this study, we aimed to identify the potential target and mechanism of ellipticine in breast cancer stem cells with a bioinformatics approach. Gene expression profiles predicting sensitivity and resistance of tumor cells to ellipticine were determined by microarray-based mRNA expressions from COMPARE. Gene list related to breast cancer stem cells was obtained from Pubmed with keywords "breast cancer stem cells". Protein-protein interaction (PPI) network construction, Gene Ontology (GO) and KEGG pathway enrichment analysis were carried out by STRING-DB. The genetic alterations of hub genes were analysed using cBioPortal. The prognostic value of the genes was evaluated using Kaplan-Meier survival curves. A Venn diagram of COMPARE microarray data and the gene list from PubMed generates two genes that are regulated by ellipticine and are related to breast cancer stem cells, namely XRCC5 and CD59. Ellipticine might target complement cascade and DNA repair mechanism in breast cancer stem cells. Ellipticine might target complement cascade and DNA repair mechanism in breast cancer stem cells. More importantly, CD59 is a potential biomarker to evaluate ellipticine bioactivity in BCSCs. Results of this study could be useful for elucidation of ellipticine molecular mechanism as well as for targeting BCSCs
The Effect of Curcumin Adjuvant Therapy on Pulmonary Function and Levels of Interleukin-6 (IL-6) and Superoxide Dismutase-3 (EC-SOD3) in Patients with Chronic Bronchial Asthma
This study was designed to evaluate the effectiveness of curcumin supplement as antioxidant and anti-inflammatory in patients with chronic bronchial asthma. Forty patients diagnosed with chronic bronchial asthma were enrolled in this study and allocated into group (1) patients assigned to receive conventional therapy of asthma, and group (2) patient assigned to receive conventional therapy of asthma combined with 750 mg curcumin supplement twice daily for two months. Pulmonary function test, asthma control test, serum interleukin-6 and serum extracellular super oxide dismutase 3 were measured before and after two months in both study groups. After two months, the mean values of pulmonary function test (spirometry) and asthma control score showed significant increase compared to pre-treatment values in group 2 patients (P<0.01). Moreover, there was marked decrease in the level of interleukin-6 in group 2 patients after two months (p< 0.05) compared to the increased in group 1 patients. The mean level of super oxide dismutase 3 didn’t show any increase in both study groups after treatment. Curcumin supplement produced improvement in pulmonary function of patients with chronic bronchial asthma along with the reduction in inflammatory status. No change in endogenous oxidative status after curcumin supplementation
Compliance with personal protective equipment use among non-medical healthcare professionals during Covid-19 pandemic
Non-medical healthcare professionals, including pharmacists, pharmacy technicians, nutritionists, and radiographers, have a high risk of COVID-19 infection during work. Personal protective equipment use has shown effective in preventing virus transmission. This study aimed to investigate the compliance with personal protective equipment use and identify the factors that may influence their compliance.
The study was designed cross-sectionally, with a self-administered questionnaire. The respondents were non-medical healthcare professionals recruited from covid and non-covid ward at Saiful Anwar General Hospital. The data were collected in November 2020. The questionnaire consists of four questions to assess compliance and eighteen questions to explore the factors that may relate to their compliance. This study used the Chi-square test to differentiate the level of compliance between two groups and binary logistic regression to analyze factors that may influence the compliance.
Most participants in this study were female (84.8%), with a median age of 33 (23 – 57) years. More than 80 % of participants worked in the non-covid ward. Only one-fifth of participants had work experience of more than 15 years. The compliance with personal protective equipment was 67.3%. In univariate analysis, factors that influenced the compliance were difficulty using, removing, and disposing of personal protective equipment, lack of training and regular monitoring, unsure about the effectiveness of personal protective equipment, uncomfortable in donning personal protective equipment. Co-workers never reminding themselves to use personal protective equipment also influence compliance. In the multivariate analysis, the difficulty of using, removing and disposing of personal protective equipment (OR 2.83 (0.730 – 3.478), p=0.025) significantly influenced compliance with personal protective equipment use
Further Understanding about the Mechanism of Vitamin D on Blood Pressure
Globally, the prevalence of vitamin D deficiency and hypertension is both increasing. Various studies have also identified that both are likely to have causality relationships. The mechanisms and possibilities of such relationships will be discussed in this article. This literature study takes systematic review and meta-analysis research as well as randomly other research to complete the discussion on the role, effects, and mechanisms of vitamin D to blood pressure. Vitamin D is a fat-soluble vitamin that can be produced by the body and the most proper measurement using 25(OH)D. Low vitamin D is one of the risk factors for increased blood pressure (BP). Administration of vitamin D seems beneficial to lowering BP through various mechanisms including inhibit renin gene expression, maintain PTH levels and calcium homeostasis, vasodilatation BP, and decrease sympathetic nerve activity. Research with vitamin D supplementation reported random data between effective and whether or not to decrease BP. Vitamin D can be significantly beneficial in only some conditions although overall it has increased levels of 25(OH)D. However, although vitamin D is very good for health improvement, the use of vitamin D specifically as an antihypertensive still needs more understanding and research on the conditions that have proven effective in their use
Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
The use of radiopharmaceuticals for infection detection has gained increasing attention for their application in nuclear medicine. The administration of [99mTc]Tc-ketoconazole may altere pharmacological aspects including interaction data with some antifungals especially ketoconazole as a common drug for candidiasis treatment. The current study investigated the ex vivo biodistribution and pharmacokinetic interaction of [99mTc]Tc-ketoconazole after ketoconazole administration in BALB/c mice. In this research,The [99mTc]Tc-ketoconazole was prepared with radiochemical purity 94.59% (n=3). The ex vivo biodistribution uptake in infected muscle as a target organ showed 0.16±0.13%ID/g for control, 0.17±0.12 for 1 h, and 0.05±0.04 for 3 h after ketoconazole administration. The Target/Non-Target (T/NT) ratio between infected muscle compared with normal muscle showed 1.19±0.13 for the control group, 2.56±1.71 for 1 h and 0.86±0.67 for 3 h. The ex vivo biodistribution also showed high radioactivity uptake on the liver, lung, spleen and kidney. Pharmacokinetics analysis using PKSolver showed [99mTc]Tc-ketoconazole half-life elimination (t1/2 beta) for the therapy group showed shorter elimination time 13.78±4.77 h compared with the control group 44.77±2.74 h after ketoconazole administration. Pharmacokinetics parameter change also occurred on the area under the curve of therapy group (AUC 0-inf) that is 26.10±18.97 %ID/g*h and maximum concentration (Cmax) 13.05±9.48 %ID/g which was related with radiopharmaceutical absorption rate. This study proves that based on biodistribution and pharmacokinetics evaluation, the [99mTc]Tc-ketoconazole application was recommended at 1 h post ketoconazole administration
Population Pharmacokinetics Modeling of Levofloxacin In Rabbit By Intravenous Bolus Injection and Peroral Administration
The population-based approach has been widely applied to describe the pharmacokinetic profile of many drugs. The aim of this current research was to study the implementation of the population-based pharmacokinetics of levofloxacin in rabbits administered by intravenous bolus injection and peroral delivery.
Modeling analyses were performed using Monolix, one of the alternative tools for the population-based approach. Monolix works based on the Stochastic Approximation Expectation-Maximization (SAEM) method. The analysis was performed based on the population model using one-compartmental and two-compartmental disposition models. The combination error model was used during the analyses. Modeling appropriateness was determined based on the goodness of fit analyses, i.e., 1) the individual fit, 2) the observed versus population prediction values; and 3) the observed versus individual prediction values
Plasma concentration profiles of levofloxacin by intravenous bolus injection and oral administration are better described by an appropriate model using a two-compartmental disposition model. All goodness of fit analyses demonstrates the power of the chosen model. However, the estimated disposition parameter values obtained based on the intravenous bolus injection and peroral administration are different for each subject. To confirm this phenomenon, we performed a simultaneous fitting of all intravenous bolus as well as peroral administration data. The goodness of fit analyses indicates an adequate fitting of all data