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INDONESIAN JOURNAL OF PHARMACY

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Published by Universitas Gadjah Mada

ISSN : 23389427 EISSN : 23389486 DOI : -

Core Subject : Health,

Medicine & Pharmacology

Indonesian Journal of Pharmacy (ISSN-e: 2338-9486, ISSN-p: 2338-9427), formerly Majalah Farmasi Indonesia (ISSN: 0126-1037). The journal had been established in 1972, and online publication was begun in 2008. Since 2012, the journal has been published in English by Faculty of Pharmacy Universitas Gadjah Mada (UGM) Yogyakarta Indonesia in collaboration with IAI (Ikatan Apoteker Indonesia or Indonesian Pharmacist Association) and only receives manuscripts in English. Indonesian Journal of Pharmacy is Accredited by Directorate General of Higher Education (DGHE) DIKTI No. 58/DIKTI/Kep/2013.

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Articles 706 Documents

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Inhibitory Activity of Sargassum hystrix Extract and Its Methanolic Fractions on Inhibiting Î±-Glucosidase Activity Azizi, Wirdatul Auliya; Ekantari, Nurfitri; Husni, Amir
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Seaweed has a great potential in the pharmaceutical field, one of them as antidiabetic. The purposed of this study was to know the inhibitory activity of Sargassum hystrix extract and its methanol fraction in inhibiting Î±-glucosidase activity. S. hystrix was extracted using methanol, then partitioned using chloroform, ethyl acetate, and methanol. Methanol fraction then separated by column chromatography to obtain the compound. The crude extract, the partitioned methanol fraction, and the column chromatography fraction were tested for its activity on inhibiting the Î±-glucosidase. The compounds of active fraction were analyzed using gas chromatography-mass spectrometry (GC-MS). The inhibitory activity (IC50) of the crude extracts and the partitioned methanol fraction were 0.35Â±0.05 and 0.02Â±0.00 (mg/mL), respectively. The column chromategraphy fractions that had an inhibitory activity to Î±-glucosidase were M2 (23.46Â±1.63%), M3 (30.88Â±4.53%), M4 (73.64Â±3.47%), and M7 (53.48Â±1.56%). GC-MS showed that the suspected compound which had inhibiting Î±-glucosidase in methanol fraction were 9-Octadecenoic acid, 1-Heptadecanecarboxylic acid,9,12-Octadecadienoic acid (Z, Z), and Octadecanoic acid methyl ester.

The Force Degradation Study of The Morpholinium 2-((4-(2-Methoxyphenyl)-5-(Pyridin-4-YL)-4H-1,2,4-Triazol-3-YL) Thio) Acetate Varynskyi, Borys; Kaplaushenko, Andriy
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

The aim of the current research was to make force degradation study of the morpholinium 2-((4-(2-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate (API) for additional confirmation of the selectivity of API and impurity determination method, propose possible structures of degradation products. Agilent 1260 Infinity (degasser, binary pump, autosampler, column thermostat, diode array detector) was used. Mass selective detector was single-quadrupole LC/MS 6120 with electrospray ion source (ESI). The chromatography study was carried out by isocratic elution with a water-acetonitrile mixture (84:16) with the addition of 0.1% methanoic acid. A column Zorbax SB-C18, 30 mm x 4.6 mm, 1.8 um. A column temperature was 40oC. The flow rate was 0.400 ml/min. The period of exposition of stress factors was four days. The period of exposition of stress factors was four days. Influence of the such factors as acid, alkali, H2O2, temperature, UV radiation on the API in bulk drug, 0.1% solution and 1% â€œsolution for injectionâ€ were studied. Dependence of content of API from a number of days of factors exposition was studied. Most destructive action was during the influence of the H2O2 and UV radiation. API was stable during the storage at laboratory conditions, acid, alkali and temperature (60oC) influence. Some degradation products structure was proposed.Â

Synthesis and in Silico Studies of a Benzenesulfonyl Curcumin Analogue as a New Anti Dengue Virus Type 2 (DEN2) NS2B/NS3 Ikhtiarudin, Ihsan
Indonesian Journal of Pharmacy Vol 30 No 2, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Curcumin has been reported can interact with multiple molecular targets involved in a large variety of diseases. Accumulated evidence indicated curcumin plays an inhibitory role against infection of numerous viruses. Some studies have been reported that curcumin can interfere the infection processes of dengue virus. In this work, a benzenesulfonyl curcumin, (3E,5E)-3,5-bis(4-methoxybenzylidene)-1-(phenylsulfonyl)piperidin-4-one (compound 2) has been synthesized by two steps of reactions. The structure of compound 2 has been established based on the interpretation of spectral data include UV, FT-IR, MS/MS, 1H and 13C NMR. Then, the in silico studies have been also performed to predict the potency of compound 2 as inhibitor for dengue virus Type 2 (DEN 2) NS2B/NS3 protease. The in silico studies showed that compound 2 has hydrogen bonding with His51 residue, and amazingly that the other catalytic triad such as Asp75 and Ser135 were also showed interactions with the ligand. It is presumably that this compound showed very good activity against DEN2 and can be developed as a new inhibitor for dengue viruses.

Cost Effectiveness Analysis of Rivaroxaban Compared to Warfarin and Aspirin for Stroke Prevention Atrial Fibrillation (SPAF) in the Indonesian healthcare setting Dwiprahasto, Iwan; Kristin, Erna; Endarti, Dwi; Pinzon, Rizaldy Taslim; Yasmina, Alfi; Thobari, Jarir At; Pratiwi, Woro Rukmi; Kartika, Yolanda Dyah; Trijayanti, Christiana
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Main drugs used in the prevention of stroke among atrial fibrillation (AF) patients are antiplatelets (aspirin) and oral anticoagulants (OAC). OAC therapy can be difficult to administer due to drug and food interactions, adds the burden of required blood monitoring, narrow therapeutic window, and requirements for dose titration. Rivaroxaban is a single-dose oral anticoagulant which does not require blood monitoring, dose titration or has dietary interactions. Phase III clinical data from the ROCKET trial have recently been reported the non-inferiority of rivaroxaban over warfarin for the prevention of strokes in AF patients. To develop an economic model evaluating the clinical and cost-effectiveness of rivaroxaban for the prevention of stroke in non-valvular AF patients in the Indonesian health care settings. We conducted cost effectiveness analysis from the perspective of payer (national health insurance). Effectiveness data used the international data from previous RCT and network metaanalysis studies. Costs data used local data of Indonesia from national health insurance’s reimbursement tariffs. Markov model was used, comprised of health and treatment states describing the management and consequences of AF. The main analysis was based on data from the phase III trials. Three months was used as cycle length. The time horizon was set at patients’ lifetime (20 years). Costs and outcomes were discounted at a 3% annual rate. Subgroup analysis and extensive sensitivity analysis was conducted. Willingness to pay (WTP) threshold in Indonesia was set as 3 times GDP of Indonesia in 2015, equal about IDR 133,375,000 per quality-adjusted life year (QALY). Base case rivaroxaban vs warfarin has ICER of IDR 141,835,063per QALY at the current cost of rivaroxaban IDR 23,500 and ICER of 130,214,687 per QALY at the proposed cost of rivaroxaban IDR 22,000. One-way sensitivity analysis showed that the key drivers of cost-effectiveness were the utility decrement applied to stable warfarin patients, discontinuation/subsequent discontinuation rates for rivaroxaban, and discontinuation/subsequent discontinuation rates for warfarin. The probabilistic sensitivity analysis suggested that rivaroxaban was cost-effective compared to warfarin in about 45% of cases at the WTP per QALY. Rivaroxaban with the proposed price of IDR 22,000 was considered to be more cost-effective when compared to warfarin.

Paricalcitol For CKD-MBD Associated With Secondary Hyperparathyroidism: A Case Series Focus On TRAP5b, b-ALP, and DKK-1 Suprapti, Budi; Hartono, Frenky; Iqbal, Muhammad; Zuhri, Muhammad Isnaini; Aditiawardana, Aditiawardana
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Chronic kidney disease (CKD) lead to secondary hyperparathyroidism (sHPT) that caused by phosphate retention and hypocalcemia. This condition known as mineral and bone disorder (CKD-MBD). The increase in parathyroid hormone would increase bone turnover that result in an increased risk of bone fractures, and vascular calcification. These will increase the levels of tartrate-resistant acid phosphatase 5b (TRAP5b), and bone-specific alkaline phosphatase (b-ALP), which is a marker of bone turnover, and also dickkopf-related protein 1 (DKK-1), which is an inhibitor of the Wnt pathway. Secondary hyperparathyroidism in CKD also caused by calcitriol deficiency. Paricalcitol is a synthetic calcitrol analogue used to reduce parathyroid hormone (iPTH) with minimal calcemic and phosphatemic activity. Vitamin D receptor activation by paricalcitol will decrease TRAP5b, b-ALP, and DKK-1. In this study we reported 9 cases of CKD-MBD with Hemodialysis (HD) and associated with sHPT. Four of nine cases received 5μg paricalcitol every HD (twice a week) while the others five is not. Level of iPTH, phosphate, calcium, TRAP5b, b-ALP, and DKK-1 were measured before initiation of study and after three months treatment. According to this study, the paricalcol administration suppresses the increase in iPTH level, bone turnover and vascular calcification showed by decreasing or supresses the increase b-ALP, TRAP5b, DKK-1 leves without increasing calcium and phosphate levels.

Determination of Classification Model and Total Phenolic Content of Local Variety Soursop (Annona muricata L.) Leaf Powder in Different Altitudes Using NIR and FTIR Spectroscopy with Chemometrics Lestyo Wulandari; Ari Satia Nugraha; Yashinta Nirmala Siswanti
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Soursop (Annona muricata L.) leaves have been widely used traditionally to overcome health problems, this is related to its total phenolic content. This study was aimed to determine the classification model and total phenolic content of soursop leaf powder of local varieties, in different altitudes using NIR and FTIR spectroscopy with chemometrics. Local variety soursop leaf samples that have been collected from low land (0-200 meter above sea level (masl)), medium land (201-700 masl) and high land (>700 masl) are prepared, then scanned using NIR and FTIR spectroscopy. Furthermore, the NIR spectra data from the samples were used as predictors on the LDA classification model of local and queen varieties soursop leaves to identify sample varieties. Samples identified as local varieties, whose total phenolic content was determined using a comparative method (UV-Vis spectrophotometry). The highest mean of total phenolic content is owned by samples from medium land (Jember) of 5.72% w/w GAE, followed by low land (Bangkalan) 2.95% w/w GAE and high land (Batu) 1, 78% w/w GAE. NIR and FTIR spectra data belonging to the samples were analyzed by chemometrics qualitatively using LDA, SVM and SIMCA, and quantitatively using PLS, PCR and SVR. The best classification and calibration model are formed from the NIR spectra data, that are the LDA model with an accuracy of 100% and the PLS model with an R-square calibration value of 0.998071 and RMSEC of 1.2735631. The LDA and PLS models are applied to the real samples. The results of the sample's total phenolic content determination obtained from the NIR spectroscopy method and UV-Vis spectrophotometry method were then tested with Paired-Samples T Test and it can be concluded that the content obtained from the two methods did not have a significant difference.

Nanocurcumin Preparation for Reducing Vcam-1 and IL-6 in High Fat Diet-Induced Hyperlipidemic Rats Dimas Adhi Pradana; Maulana Ardhi; Arifa Caryn Dea Utami Hasyono; Dzihni Meytasari; Farah Deastasa Nabilah; Rochmy Istikharah; Lutfi Chabib
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Hyperlipidemia is a pathological condition due to lipid metabolism abnormalities. Increased and oxidized LDL in hyperlipidemia will trigger an inflammatory response and produce proinflammatory cytokines, such as vascular cell adhesion molecule-1 (VCAM-1) and Interleukin-6 (IL-6). Curcumin can be used as antioxidants, anti-inflammatory and antihyperlipidemia, but as it is practically insoluble in water, formulation of curcumin nanosuspension is made to improve the effects of curcumin therapy. This study was conducted to determine the activities of nanocurcumin preparation as preventive measures for rats induced with hyperlipidemia. The test animals used were 49 male Wistar rats divided into 7 test groups: normal control group, negative control group, 80mg/kg BW/day curcumin control group, and nanosuspension curcumin dose of 80mg/kg BW/day, nanoemulsion curcumin dose of 80mg/kg BW/day, SNEDDS curcumin dose of 80mg/kg BW/day and solid lipid nanoparticles dose of 80mg/kg BW/day. Provision of preventive measure was performed on days 1-67. On day 11-67, the induction of lard and egg yolk (1:1) was administered with a volume of 2mL/200g of rat BW. On the 68th day, blood samples were taken for the determination of VCAM-1 and IL-6 parameters using Biotin-Streptavidin-Amplified Enzyme-Linked Immuno-sorbent Assay method. Data analysis of VCAM-1 and IL-6 levels between test groups were conducted by means of normality test and One-way ANOVA (p<0.05). Based on the data of VCAM-1 and IL-6 levels, nanocurcumin dose of 80mg/kg BW preparation was able to significantly improve the preventive activity of curcumin compared to curcumin suspension dose of 80mg/kg BW by reducing VCAM-1 levels in SNEDDS (53.260%), nanoemulsion (52.737%), nanosuspension (52.325%) and solid lipid nanoparticles (51.444%) and decreasing IL-6 levels in SNEDDS (33.030%), nanoemulsion (31.568%), nanosuspension (29.898%), and solid lipid nanoparticles (28.875%).

Conjugation of Anti-EpCAM Antibody on Alginate–RIP MJ-30 Nanoparticle through Carbodiimide Reaction as a Model of Targeted Protein Therapy Ismail, Hilda; Ciptasari, Ummi H.; Ikhsan, M Arief Nur; Suryani, Fidya; Sismindari, Sismindari; Martien, Ronny; Yuswanto, Ag
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Ribosome inactivating proteins from Mirabilis jalapa L. (RIP MJ) has shown higher cytotoxic activity when being formulated as a nanoparticle. However, the selectivity of the delivery system is also an important aspect when it comes to cytotoxic cell therapy. Epithelial cell adhesion molecule (EpCAM) is a monomeric glycoprotein which is overexpressed in epithelial cancer cells. This study aim was to develop a model of targeted protein delivery system by formulating the base fraction of RIP MJ (RIP MJ-30) into alginate nanoparticles and conjugating it with anti-EpCAM antibody. RIP MJ-30 was formulated in to nanoparticle using alginate and CaCl2 as cross-linker. Optimization of conjugation reaction condition was done in the pH variation of 4.5, 5.5, and 6.5. The success of conjugation was analyzed qualitatively using native polyacrylamide gel electrophoresis (native-PAGE) method and BCA assay. The optimum formula of RIP MJ-30 nanoparticles was produced using 0.3% alginate and 0.2% CaCl2. Results indicated that optimum conjugation reaction was carried out at pH level of 5.5. The optimum native-PAGE condition was by using 8% polyacrylamide gel in duration of 6h. Characterization of nanoparticle resulted in particle size of 205.0nm, zeta potential of -6.9mV, entrapment efficiency of 71.11±4.84%, and conjugation efficiency of 89.55±6.18%. It was concluded that RIP MJ-30 was successfully formulated into alginate nanoparticle and conjugated to anti-EpCAM antibody through carbodiimide reaction using 1-ethyl-(dimethylprophilamine) carbodiimide (EDAC).

The Properties of Brown Marine Algae Sargassum turbinarioides and Sargassum ilicifolium Collected From Yogyakarta, Indonesia Artemisia, Rahma; Nugroho, Akhmad Kharis; Setyowati, Erna Prawita; Martien, Ronny
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Brown marine algae are the prominent source of marine natural products that have bioactive metabolites. Sargassum turbinarioides and Sargassum ilicifolium were dominated in Indonesia as brown marine algae that well known as a source of fucoidan. The samples were collected from Gunungkidul, Yogyakarta, Indonesia. In this study, we investigated and identified the yield of aqueous crude and purified extracts using different extraction temperatures (60°C, 70°C, 80°C, 90 °C). The highest yield of S. turbinarioides crude extract (7.36%) was obtained at temperatures 90 and 80 °C while the highest yield of S. ilicifolium was 3.49 % at 80 °C. The presence of sulfate polysaccharide in Sargassum turbinarioides is 3,78 % and Sargassum ilicifolium is 2,93 %. Each of the extract was screened using phytochemical detection, Thin Layer Chromatography (TLC) and Fourier transform infrared spectroscopy (FT-IR) analysis. The phytochemical detection indicated that Sargassum ilicifolium has bioactive metabolites such as carbohydrates, proteins and amino acids, terpenoid, phenolic compounds, and flavonoids. The FTIR spectrum of the S. turbinarioides and Sargassum ilicifolium extract refer to the presence of ester sulfate groups through showing peaks at 1300 to 1200 cm-1 and 980 to 950 cm-1. The result indicated that Sargassum turbinarioides and Sargassum ilicifolium contain of sulfate polysaccharide were prospect a biological activities to use for the development of marine nutraceutical drugs especially as antioxidant.

The Effect of Thionamide to TRH, TSH, IL-4, T-REG, and Anti-TPO in Graves’ Disease Eva Decroli; Dwitya Elvira; Dinda Aprilia
Indonesian Journal of Pharmacy Vol 30 No 2, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

The most common cause of hyperthyroidism is Graves' disease. TRH and TSH are hormonal factors that modulate and control thyroid function in Graves' disease. In the immunological aspect, Graves' disease is played by the role of T-reg, IL-4, and anti-TPO. Graves' disease treatment goal is to inhibit thyroid hormone secretion by administering thionamide. The evaluation of this treatment is its hormonal and immunological aspects. To describe the effect of thionamide on serum TRH, TSH, IL-4, T-reg, and anti-TPO levels in Graves' disease. This study is a clinical trial study in 25 study participants. All study participants were given thionamide, namely PTU 300mg for three months and blood samples were taken for laboratory tests. Serum TRH, TSH, IL-4, T-reg FOXP3, and anti-TPO levels were examined by ELISA. The mean levels at the beginning and after three months of therapy are: serum TRH 92.589pg/mL and 115.944pg/mL; serum TSH 0.041mU/L and 0.223mU/L; serum IL-4 19.759pg/mL and 23.040pg/mL; T-reg FOXP3 gene polymorphism 0.621ng/mL and 0.518 ng/mL; serum anti-TPO 2697.539pg/mL and 2604.710pg/mL. Increased levels of serum TRH and TSH levels were statistically significant. The change in serum IL-4, T-reg FOXP3 gene polymorphism, and anti-TPO levels were not statistically significant. The administration of thionamide in Graves' disease for three months will significantly decrease Wayne index and serum FT4 levels, increase serum TRH and TSH levels.

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