Indonesian Journal of Pharmacy

Journal Information
ISSN / EISSN : 2338-9427 / 2338-9486
Current Publisher: Universitas Gadjah Mada (10.22146)
Former Publisher: Indonesian Society for Cancer Chemoprevention (10.14499) , Universitas Gadjah Mada (10.14499)
Total articles ≅ 257
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Yulias Ninik Windriyati, Matsniyyatul Badriyah, Diar Arum Kusumaningtyas, Rian Lesta Riesmalia
Indonesian Journal of Pharmacy pp 305–311-305–311; doi:10.22146/ijp.1138

Abstract:
The dissolution of atorvastatin calcium need to be improved since included BCS Class II drugs with low solubility and high permeability, meaning that the dissolution affects the bioavailability of drugs. This research aimed to develop a formulation of a liquisolid tablet using PEG 400 as a solvent and some carrier materials in various compositions to increase the dissolution of atorvastatin calcium. Different formulations of liquisolid tablets were conducted using different quantities of carrier and coating material for adsorbing liquid solvent to produce a free-flowing and compressible powder. Avicel PH 101, Avicel PH 102, Neusilin US2 were employed as the carrier and Aerosil 200 as the coating material. A disintegrant and lubricant were then added to the formed liquisolid system and compressed into tablets by the direct compressing method. The liquisolid tablets were characterized for their tableting properties and possible drug-excipient interaction by XRD and FTIR analysis. The tableting characteristics of atorvastatin calcium liquisolid tablets were within the acceptable limits criteria. The dissolution of AA4 and NA1 liquisolid tablets was higher compared to marketed tablets. Based on the XRD and FTIR analysis, no interactions between drug and excipient.
Reni Ariesta, La Ode Muhammad Fitrawan, Agung Endro Nugroho, Suwidjiyo Pramono
Indonesian Journal of Pharmacy pp 312-322; doi:10.22146/ijp.1135

Abstract:
Many medicinal plants are widely grown in South- and Southeast Asia countries. Some of them are traditionally used for treatment of diabetes mellitus such as Andrographispaniculata and Centellaasiatica. In the study, we provided fractionated-extracts of A. paniculata and C. asiatica to increase the concentration of their active compounds and eliminate unexpected substances. The aim of the study was to evaluate the antidiabetes effect of the combination of their fractionated-extracts in male neonatal streptozotocin (STZ)-induced diabetic rats. In the study, diabetes was injected intraperitoneally 90mg.kg-1 BWSTZ to two day-old rats. At the age of three months, the rats were administered with the combination of both fractionated-extracts for 14 consecutive days. We evaluated antidiabetes with parameters of blood glucose levels, morphology of pancreatic islet, β-cell density as well as immunohistochemical pancreatic insulin. The levels of MDA, SOD and GPx were also determined about oxidative stress change after treatment with the combination. In the study, the combination succeeded to lower the blood glucose level in neonatal STZ-induced diabetic rats. Inline with fact, improvement of rat pancreatic islets and β cells density, as well as moderate restoration of pancreatic insulin, were observed after treatment with the combination. The substance could decrease the level of MDA, and increase the levels of SOD and GPx. In conclusion, the combination of fractionated-extracts of A. paniculata and C. asiatica exhibited potential antidiabetic effect to its antioxidative effect in male neonatal STZ-induced diabetes rats.
Irfan Kesumayadi, Luh Ayu Nanamy Khrisnashanti Eva Susila, ErickO Hartanto, Darmawati Ayu Indraswari
Indonesian Journal of Pharmacy pp 290-296; doi:10.22146/ijp.980

Abstract:
Gas pollutants that accumulate in the room with restricted air circulation may cause respiratory system disorders. A pregnane glycoside compound from Sansevieria can reduce the pollutants. This study aims at producing gels from Sansevieria extract to neutralize indoor gas pollutants. Sansevieria extract is produced by the maceration process with composition 8 g simplicia and 100 ml ethanol 96%. The extract was processed into the gel with a 20% concentration. The gel was applied to rats (Rattus norvegicus) Wistar strain induced by cigarette, coal, and mosquito smoke with positive control and treatment groups. After 8 days, the Gross examination and histopathology of lungs and liver were observed quantitatively. MDA levels were measured with the TBARS method. Data were analyzed by independent sample T-test and Mann-Whitney test with p-value considered significant if
Sarmoko Sarmoko, Iin Solihati, Joko Setyono, Heny Ekowati, Arif Fadlan
Indonesian Journal of Pharmacy pp 266-272; doi:10.22146/ijp.859

Abstract:
One of the main chemotherapy agents for colon cancer is 5-fluorouracil (5-FU). However, the effectiveness of 5-FU decreased; therefore, co-chemotherapy with another agent is needed to enhance the activity. This study aims to determine the effect of red ginger extract as a co-chemotherapy agent with 5-FU on WiDr colon adenocarcinoma cells. We investigated the cytotoxic activity of the ethanolic extract of rhizome red ginger and combination with 5-fluorouracil (5-FU) in WiDr human colorectal cancer cell line. Red ginger extract was extracted by using 96% ethanol. Cytotoxic assay of red ginger extract and 5-FU was performed using MTT assay for 24 and 48 hours. Treatment of 5-FU in WiDr cells for 48 hours showed an IC50 value of 130 µg/mL, while no IC50 value was obtained for the 24 hours treatment. Treatment of red ginger extract with an incubation time of 24 and 48 hours had a cytotoxic effect on WiDr cells with IC50 values of 68 µg/mL and 65 µg/mL, respectively. The combination of 1000 μg/mL 5-fluorouracil with 35 μg/mL red ginger extract at 24-hour incubation resulted in a smaller cell viability value than every single treatment. The combination treatment of 5-FU 60 μg/mL with red ginger extract at a 25 μg/mL concentration causes a more significant decrease in cell viability than a single 5-FU treatment. In conclusion, red ginger extract may increase the cytotoxic activity of 5-FU in colon adenocarcinoma WiDr cells.
Roihatul Mutiah, Wahyi Yucha Firsyaradha, Riza Ambar Sari, Rahmi Annisa, Risma Aprinda Kristanti, Yen Yen Ari Indrawijaya, Tias Pramesti Griana, Anik Listiyana
Indonesian Journal of Pharmacy pp 257-265; doi:10.22146/ijp.1120

Abstract:
It is known that Eleutherine palmifolia (L.) Merr contains flavonoid and polyphenol as bioactive compounds that have the ability as chemopreventive agents. This study aims to examine the effect of Eleutherine palmifolia (L.) Merr extract (EPE) on colon histopathology and the enhancement of caspase-3 expression in BALB/c mice of colitis-associated colon cancer (CAC) model. Thirty Balb/c female mice were used in this study and were divided into six groups. Five mice in one group were normal or negative control (given phosphate-buffered saline), and twenty-five mice were induced intraperitoneally with 10 mg/kg BW AOM (Azoxymethane), and it was followed by the administration of 5% DSS (Dextran Sodium Sulfate) every two weeks for 20 weeks. At the sixth week, one mice in each group was sacrificed for the Fecal Occult Bold Test (FOBT) and serum amyloid α (SAA) test to ensure that CAC was indeed formed. The administration of EPE with varying doses was started from the eighth week and was continued until the 21st week. The length of the colonic crypt was measured through histology appearance using Hematoxylin-eosin (HE) staining while the immunohistochemical method was used to observe apoptotic activity through the enhancement of caspase-3 expression. The results showed that the increase in EPE dosage also increased the crypt colon length compared to the positive control group. The administration of 1.00 mg/20gBW EPE significantly increased cell apoptosis which can be observed through caspase-3 expression compared to the positive control group (p
Fajar Fakri, Loly Subhiaty Idrus, Maria Alexandra Iskandar, Indra Wibowo, I Ketut Adnyana
Indonesian Journal of Pharmacy pp 297–304-297–304; doi:10.22146/ijp.1121

Abstract:
Keladi tikus (Typhonium flagelliforme (Lodd.) Blume) is an Indonesian medicinal plant that has various pharmacological properties. Zebrafish (Danio rerio) has been proposed as a model that can bridge the gap between cell assays and rodent assays. Evaluation of the toxic effects of natural products using the Zebrafish model can be assessed starting from the blastula stage of embryonic development. This study aims to investigate the potential acute toxicity effect of keladi tikus-ethanol extract (KTEE) using zebrafish embryos. A static non-replacement regime for acute toxicity testing was used. Wild-type zebrafish embryos were exposed to various concentrations of KTEE (50, 100, 200, 400, 800, 1600 µg/mL) starting at 6 hours post-fertilization (hpf) until 96 hpf. The results showed that the survival rate of zebrafish embryos decreased as the concentration of the test extract increased. The LC50 values of KTEE were 494.553 µg/mL at 96 hpf and 555.787 µg/mL at 72 hpf. Embryotoxicity effect of KTEE includes hatching delays and decreased heartrate on zebrafish embryos, especially at high concentrations. KTEE also caused abnormalities in embryo morphology, including pericardial edema, jaw and tail deformity.
Muhammad HabiburRahman, Vivian Soetikno, Wani Riselia Sirait, Missy Savira
Indonesian Journal of Pharmacy pp 335–353-335–353; doi:10.22146/ijp.1123

Abstract:
Gonorrhea is one of the most often sexually transmitted infection in the world. In 2016, WHO stated the Southeast Asia region as the fourth-highest incidence rate and prevalence of gonorrhea. One of the current problems with gonorrhea is related to its emerging resistance to first-line drugs such as cephalosporins, macrolides, and fluoroquinolones. This resistance has an impact on the difficulty of finding effective antibiotics to eradicate the infection, thus risking financial loss and infertility in sexually active age patients. This literature review will discuss solithromycin, the first fluoroketolide in phase III clinical trial, and show its potential as a new antibiotic against infection with resistant Neisseria gonorrhoeae. Literatures are searched using Pubmed and Google Scholar search engines with keywords: antibiotics, CEM-101, clinical trial, Neisseria gonorrhoeae, new treatment, pharmacology, pharmacokinetics, resistance, safety, and solithromycin. This semisynthetic antibiotic is supported by a different chemical structure from previous macrolides; improving solithromycin becomes more stable and able to bind easier with bacterial ribosomes. Pharmacologically, solithromycin provides an advantage in its high bioavailability, easy oral administration route, wide distribution, metabolism mainly in the liver, but not required dosage adjustments due to hepatic impairment, and a single dosage preparation that can increase patient compliance in healing gonorrhea infections. Also, its lower MIC50 than previous antibiotics makes it well-tolerated, therefore making this antibiotic as a potential recommendation for the management of multi-drug resistant gonorrhea in the future. Solithromycin is not inferior to the standard therapy (ceftriaxone and azithromycin), with 80% vs. 84% gonorrhea eradication rates. Per the anatomic site, the eradication rate is 92% in genital, 94% in the pharynx, and 83% in the rectum. However, special attention needs to be paid to the side effects of the gastrointestinal tract of solithromycin, as observed in phase III clinical trials at a dose of 1000 mg in the form of diarrhea (24%) and nausea (21%).
Tarsa Ruli Tambunan, Jaka Widada, Ema Damayanti, Tutik Dwi Wahyuningsih, Mustofa Mustofa
Indonesian Journal of Pharmacy pp 273-280; doi:10.22146/ijp.634

Abstract:
Low molecular weight (LMW) antiplasmodial compounds isolated from bacteria, particularly Streptomyces have not been widely reported. This study aimed to identify LMW compounds from Streptomyces sp. GMR22 as antiplasmodial. Isolation of the LMW compounds from the supernatant of fermentation culture using solvent of n-hexane:ethylacetate (EtOAc) (85:15v/v)and identified using gas chromatography-mass spectrometry (GC-MS). Antiplasmodial assay of n-hexane:EtOAc extract was carried out in vitro against P. falciparum (3D7). Parasitemia percentage obtained through microscopic observations and 50% inhibitory concentration (IC50) obtained through probit analysis. The antiplasmodial confirmation test was done by flow cytometry using SYBR Green I for Plasmodium DNA and anti-human CD235a for erythrocytes. The LMW compounds were investigated using SwissADME for drug-likeness. n-Hexane:EtOAc extract contained 21 LMW compounds from alcohol, hydrocarbon, ester, aromatic/diester, diester, fatty acid, and triester classes, which possessed moderate antiplasmodial activity with an IC50 value of 38.61 ± 19.06 µg/mL. Confirmation by flow cytometry analysis showed that the extract at 50 µg/mL exhibited antiplasmodial activity based on a decreased Plasmodium DNA intensity as compared to the control group. The result of drug-likeness screening obtained that 3 LMW compounds were drug-likeness, namely phenylethyl alcohol, ethyl citrate, and di-n-butyl phthalate. Streptomyces sp. GMR22 produced LMW compounds as antiplasmodial, and further study was needed for identification of antiplasmodial active compounds.
Febri Wulandari, Muthi' Ikawati, Dhania Novitasari, Mitsunori Kirihata, Jun-Ya Kato, Edy Meiyanto
Indonesian Journal of Pharmacy pp 244-256; doi:10.22146/ijp.681

Abstract:
An improved compound of pentagamavunone-1 (PGV-1), chemoprevention-curcumin analog 1.1 (CCA-1.1), has been synthesized and proven to have antiproliferative effects against breast cancer cells. This study is designed to investigate the potency of CCA-1.1 alone and in combination with doxorubicin (Dox) on T47D cells in comparison with that of PGV-1. We used the MTT assay to assess cytotoxic activity. Propidium iodide (PI), annexin-V–PI, and DCFDA staining were respectively used to determine cell cycle profiles, apoptosis, and intracellular reactive oxygen species (ROS) levels. Senescent cells were identified using the SA-b-galactosidase assay. Our results revealed that CCA-1.1 possesses cytotoxic effects similar to those of PGV-1 on T47D cells. Synergistic effects during co-treatment with Dox were also observed. CCA-1.1 arrested cell cycle progression at the G2/M phase and limited sub-G1 accumulation, which is correlated with apoptosis. CCA-1.1 alone and in combination with Dox increased senescence and intracellular ROS to a similar level to those achieved by PGV-1. CCA-1.1 alone and in combination with Dox enhanced cytotoxic activity toward T47 cells compared to PGV-1. Thus, this curcumin analog may be a potential chemotherapeutic/co-chemotherapeutic candidate for estrogen receptor-positive (ER+) breast cancer therapy.
Mohammad Anwarul Basher, Rafiul Hoque, Roni Roy, Sazzad Hosen, Irin Karim, Tanaya Bhowmik, Afroza Akter
Indonesian Journal of Pharmacy pp 323–334-323–334; doi:10.22146/ijp.602

Abstract:
Schumannianthus dichotomus (Roxb.) is a perennial shrub from Marantaceace family. In traditional medicine, rhizome of the plant is used in fever and stem is used in earache. We aimed to substantiate these therapeutic claims by examining their effects in mice model. Antinociceptive effect was evaluated by three pain models and antipyretic effect was tested by yeast induced hyperthermia experiment. Influence of mice sexes on these pharmacological effects was examined by performing experiments separately on male and female mice. Quantitative analyses of total phenols and flavonoids were performed. Antinociceptive effects showed striking sex dimorphism. In hind paw licking test, male mice showed significant reductions in licking in both phases for both rhizome and stem extracts while significant effect was observed only in late phase in female mice. In writhing test, antinociception is more profound in male than in female. In hot plate test, stem was more effective than rhizome in male mice while female mice produced little effect for both extracts. Antipyretic experiment also showed varied effect in male and female mice; both extracts showed significant decrease in body temperatures. Rhizome showed greater effect in female mice while stem was more effective in male mice. Total phenol and flavonoid in rhizome were found 103.08 mg GAE (gallic acid equivalent) and 9.07mg QE (quercetin equivalent) respectively while in stem, these were 43.39mg GAE and 20.93 QE. Antinociceptive and antipyretic effects of rhizome and stem extracts endorsed the traditional uses of S. dichotomus. Also, differential effects based on mouse sex indicate the prerequisite of both male and female mice model in therapeutic evaluations of plant extract.
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