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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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OPTIMIZATION AND IN VIVO EVALUATION OF MESALAMINE pH DEPENDENT COATED PELLETS FOR PROMISING ILEOCECAL TARGETING Gangurde, Hemant H; Chordiya, Mayur Ashoka; Tamizharasi, S.; Sivakumar, T.
INDONESIAN JOURNAL OF PHARMACY Vol 24 No 4, 2013
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

The present research is a challenge to design, optimized and evaluates mesalamine loaded burst release pH dependent coated pellets for possible ileo-cecal targeting to treat effectively Crohnâs disease. The novelty of this formulation is to release drug specifically and instantly in ileo-cecal region where the chances of Crohnâs disease is more frequent, without being released in upper gastrointestinal tract. Preliminary experimental batches are studied for micromeritic properties and in-vitro drug release. FormulationÂ showed desirable lag time of 5h and dissolution profile were further optimized by applying 32 full factorial design to study the effect of extent of coating (% w/w) Eudragit S100 and croscarmellose sodium over drug layered pellets. The regression equation generated for Q300 (lag time of 5h) = +5.72-31.97*A+0.82*B-0.49*A*B+26.36*A2-0.15*B2 and for Q390 (90% of drug release at pH7.2 within 90 minutes after lag time) = +84.63- 40.09*A+4.62*B. The drug release data of optimized formulation were close to that predicted by the model. Various kinetic models were applied to the all optimized batches. In vivo evaluation of optimized formulations was performed to assess macroscopic, microscopic and biochemical parameters in rats and performed. The present study demonstrates that the mesalamine enteric coated pellets successfully targeted at ileo-cecal region.Key words: Mesalamine, pulsatile, ileo-cecal targeting, celpheres, Croscarmellose sodium, eudragit S100

Detection of apoptosis mechanism on renal cancer cell treated by 16,17-dehydrodeacetyl-5α-oleandrin compound isolated from Nerium indicum Mill. Leaves. Mae S.H. Wahyuningnsih; Sofia Mubarika; Ibnu G. Gandjar; Subagus Wahyuono; AWM. Boersma; K. Nooter
Indonesian Journal of Pharmacy Vol 19 No 4, 2008
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

The 16,17-dehydrodeacetyl-5α-oleandrin was isolated from an active fraction of Nerium indicum Mill leaves (fam. Apocynaceae). This compound was cytotoxic against various cancer cells, and selective on A498 cells (Renal cancer). However, the apoptosis mechanism was still unknown yet. Therefore, the aim of this study was to know the apoptotic mechanism of 16,17-dehydrodeacetyl-5α-oleandrin on A498 cells by FITC labeled annexin V and immunucytochemical assays. The detection of apoptotic mechanism on A498 cells was performed with FITC-conjugated annexin V using Flow Cytometry. The p53 protein expression were detected using immunocytochemical. Treatment with 16,17-hydrodeacetyl-5α-oleandrin (3.88 x 10-4 mM) using FITC-annexin V increased the percentage of the dead cells in the 24th and 48th hours incubation period. The 16,17-dehydrodeacetyl-5α-oleandrin (1,94x10-4 and 3,88x10-4 mM) raised significanly p53 protein expression (p<0,05). The percentage of the p53 protein expression increased throughout the time of samples incubation.Key words: 16,17-dehydrodeacetyl-5α-oleandrin,fluorescein isothiocyanate-annexin V, immunocytochemically, A498 cells.

QSAR MODELING OF 2-[CH(OH)X]-5,8-(OY)2 -1,4-NAPHTHOQUININES AGAINST L1210 CELLS USING MULTIPLE LINEAR REGRESSION Ajeet .; Brajpal Singh; Vipul Kumar
Indonesian Journal of Pharmacy Vol 23 No 3, 2012
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Quinones are present in many drugs such as anthracyclines, daunorubicin, doxorubicin, mitomycin, mitoxantrones and saintopin, which are used clinically in the therapy of solid cancers. The cytotoxic effects of these quinone are mainly due to the inhibition of DNA topoisomerase-II. It is the necessity to develop the 1,4-Naphthoquinone analogues with Cytotoxic effect. Here 2-[CH(OH)X]-5,8-(OY)2-1,4-Naphthoquinines analogues have been used to correlate the cytotoxic activity with the Eccentric Connectivity index (ECI), Fragment Complexity (FC) and McGowan Volumes (MG) for studying the Quantitative Structure Activity Relationship (QSAR). Correlation may be an adequate predictive model which can help to provide guidance in designing and subsequently yielding greatly specific compounds that may have reduced side effects and improved pharmacological activities. We have used Multiple Linear Regression (MLR), one of the best methods for developing the QSAR model. Results from this QSAR study have suggested that ECI, FC and MG are the important descriptors for cytotoxic activities of 1,4-Naphthoquinones against L1210 cells. For the validation of the developed QSAR model, statistical analysis such as data point-descriptor ratio, fraction of variance, cross validation test, standard deviation, quality factor, Fischer’s test; and internal validation such as Y-randomization test have been performed and all the tests validated this QSAR model.Key words: 1,4-Naphthoquinones, QSAR, Eccentric connectivity index, Fragment complexity, McGowan Volume, Multiple Linear Regression

The cytotoxic and antiproliferative effects of gamavuton-0 in rat basophilic Leukemia cells Agung Endro Nugroho; Sardjiman .; Kazutaka Maeyama
Indonesian Journal of Pharmacy Vol 20 No 2, 2009
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Gamavuton-0 (GVT-0), also named as 1,5-bis(4’-hydroxy-3’- methoxyphenyl)-1,4-pentadiene-3 one is a 1,5-diphenyl-1,4-pentadiene-3-one analog of curcumin by modifying the center site of curcumin leading to 1,4-pentadiene-3-ones to maintain the hydroxy moiety at aromatic rings which are responsible for its biological activities. Curcumin has been reported to have potent anticarcinogenic effects. Besides, curcumin was found to induce apoptosis in human Leukemia cells. In our study, we investigated the cytotoxic and antiproliferative effects of gamavuton-0 in rat basophilic leukemia cells. Cell viability was determined by WST-1 assay. In brief, tetrazolium salts were cleaved to formazan by cellular enzymes of viable cells, determined by colorimetric methods with a microplate (ELISA) reader at 450 nm.In the present study, we evaluated cytotoxic and proliferative effects of GVT-0 in rat basophilic leukemia cells. In the study, GVT-0 induced rat basophilic leukemia cells death in a dose dependent manner after overnight incubation. GVT-0 also impaired the content of histamine and b-hexoaminidase enzyme in cells. However, the cytotoxic effect of GVT-0 (IC50 : 43,67 mM) was less potent than this of curcumin (IC50 : 29,14 mM). GVT-0 (1 mM) also showed a significant inhibition of cell growth after 48 and 72 hr. Its fact indicates that GVT-0 could prolong the cells doubling time. These results provide useful information to guide the development of new synthetic compounds for the treatment of cancer diseases.Key words : gamavuton-0, curcumin, cancer, cytotoxic, antiproliferative,

DEVELOPMENT AND VALIDATION OF A HPLC METHOD FOR DETERMINATION AND QUANTIFICATION OF RUBRAXANTHONE IN STEM BARK EXTRACT OF MANGOSTEEN Meri Susanti; Dwisesaria Irma Lena; Dachriyanus Dachriyanus
Indonesian Journal of Pharmacy Vol 25 No 4, 2014
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Rubraxanthone is one of antibacterial and antioxidant compound which is isolated from stem bark of mangosteen (Garcinia mangostana Linn.). The precise method for analysis of plant constituents is normally a reverse-phase high performance liquid chromatographic (RP-HPLC). Development and validation of a RP-HPLC method for chromatographic separation was carried out on a reversed-phase column Shimadzu ® Shimp-pack VP – ODS (4.6x250mm) using an isocratic mobile phase of 0.4% formic acid - acetonitrile at a flow rate 1mL min-1, and detection was with a UV detector. The linearity of the proposed method was found in the range of 2.5-25μg/mL-1 with regression coefficient 0.999. Intraday precision studies showed the relative standard deviation ≤1.58% and inter-day ≤3.20%. Accuracy of the method was determined by a recovery study conducted at 3 different levels, and the average recovery was 102.18%. The Limit of Detection Limit of Quantitation (LOQ) and were 0.47 and 1.56μg/mL-1.The contents of rubraxanthon in the crude was 0.23±0.07%w/w.

EXPRESSION OF MODIFIED RECOMBINANT HUMAN ERYTHROPOIETIN IN CHO-K1 CELLS AND ITS IN VITRO PROLIFERATION ASSAY IN TF-1 CELLS Adi Santoso
Indonesian Journal of Pharmacy Vol 25 No 1, 2014
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Erythropoietin (EPO) is a 30 kDa glycoprotein hormone which is important for red blood cells maturation. EPO consists of 165 amino acids and possesses 3N-linked carbohydrate chains. Recombinant human erythropoietin (rHuEPO), such as epoetin-α and epoetin-β, have been used for many years to treat anemia in patients with chronic renal failure, systolic heart failure, HIV-AIDS, or cancer. In vivo stability of rHuEPOs were low due to rapid metabolisms by galactosyl receptor of the hepatocytes. Previously, a novel erythropoiesis stimulating protein (NESP) called darbapoetin-α (DARB) which possesses two additional N-linked glycosylation had been studied. It was observed that NESP showed better in vivo stability and biological activity compared to the unmodified form (containing only 3N-linked carbohydrate chains). Based on the above study, we attempted to synthesize recombinant human EPO (rHuEPO) by generating CHO-K1 cell lines expressing codon-optimized human epo open reading frame (ORF) in CHO-K1 cells. The ORF was modified to contain 5 N-linked carbohydrate chains. The media obtained from CHO-K1 cell culture was collected and diafiltrated with the use of tangential flow filtration. The rHuEPO protein containing polyhistidine tag was purified using affinity chromatography. An SDS/PAGE and Western blotting analyses confirmed that the purified protein was the modified rHuEPO. MTT based proliferation assay was conducted in TF-1 bone marrow cell line as a model. The result showed that the modified rHuEPO was able to enhance TF-1 cells proliferation.Key words: CHO-K1, erythropoietin, glycosylation, MTT assay and TF-1 cell line.

DEVELOPMENT AND VALIDATION OF LIQUID CHROMATOGRAPHY AND SPECTROSCOPIC METHODS FOR THE ANALYSIS OF DOXOFYLLINE IN PHARMACEUTICAL DOSAGE FORMS Ethiraj Thiruvengadam; Revathi Ramadoss; Ganesan Vellaichamy
Indonesian Journal of Pharmacy Vol 24 No 1, 2013
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

A high performance liquid chromatography (HPLC) and ultraviolet spectroscopic (UV) methods were developed and validated for the quantitative estimation of doxofylline (DF) in pharmaceutical dosage forms. HPLC was carried out using reversephase technique on RP-8 column with a mobile phase composed of 0.05M phosphate buffer pH 6 and acetonitrile (60:40, v/v). The mobile phase was pumped at a flow rate of 1mL/min, and detection was made at 230nm with PDA detector. UV method was performed with λ max at 270nm with apparent molar absorptive of 0.878x103 L mol-1 cm-1. Both the methods showed good linearity, recovery and precision. No spectral or chromatographic interferences from the tablet excipients were found in UV and HPLC methods. The various parameters such as linearity, precision, accuracy, specificity, and robustness, limit of detection and limit of quantization were studied according to ICH guidelines. Statistical analysis was done by student’s t-test and F-test, which showed no ignificant difference between the results of both methods. So the proposed methods could be applicable for routine analysis of DF and monitoring of the quality of marketed drugs. Key words: Doxofylline, Validation, HPLC, UV spectroscopy, Comparisonstudies, Student’s t-test, F-test.

The effect of avocado butter to stability of avocado emollient cream Teti Indrawati; Yuanita Sari
Indonesian Journal of Pharmacy Vol 22 No 2, 2011
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

The characteristic of emollient cream that contained of avocado butter as anti-aging is influenced by amount of avocado butter used. The research has a purpose to exploit and develop usage of avocado butter in the field of cosmetic. The research has done by making A/M cream used 1-11% avocado butter with melting and mixing method at temperature of 70-75 °C. Stability of product creams were be evaluated, and tested with accelerated test using elevated temperature. The result showed that concentration of avocado butter between 1-11% can be made become W/O emollient cream. The cream stability was progressively influenced by amount of avocadobutter, the increasing of avocado butter would make progressively good stability, the stability go down at 7% concentration. The best stability creams has shown by cream that contain 5% avocado butter,Key words: avocado butter, A/M cream type, emollient cream, stability of cream

Secondary metabolite (antibiotic) production by Indonesian endophytic fungi Sebastian Margino
Indonesian Journal of Pharmacy Vol 19 No 2, 2008
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Endophytic microbes is a potentially new field for producing the promising secondary metabolite and a few people utilizing them. The purpose of this research is to find out the fungi which have an ability to produce new pathogenic eukaryote inhibiting antibiotic. The researches steps were isolation, selection based on the ability of isolates to utilize carbonsources and their inhibitory effect by bioassay test with indicator microbes such as Fusarium oxysporum f.sp. licopersicae, Bacillus subtilis and Candida albicans. Selected isolates was determined by their inhibitory effect value was more than 4.0. Paper chromatography technique was applied to analysis the character of antibiotic using many kinds of eluents. Optimization was done to increase the production and inhibitory effect of produced antibiotic. Isolation research step found 86 endophytic fungi isolates from many kinds of plants tissue from Yogyakarta. Selection results showed that 9 isolates had inhibitory effect value more than 4.0 and four isolates that were JA-2, MB-1, NGK-1 and KMD-7 higher than 5.0. Antibiotic production was influenced by carbon sources or kinds of substrates, for examples JA-2 isolate grown at PDB medium produced higher inhibitory effect to B. subtilis than Antibiotic-3 and GY; NGK-1 grown at Antibiotic-3 medium produced higher inhibitory effect to B. subtilis and C. albicans than others; MB-1 grown at Antibiotic -3 medium produced higher inhibitory effect to F. oxysporum than others. Finally isolates JA-2 and NGK-1 was chosen as selected isolates for development of new antibiotic.Key words : Secondary metabolite, endophytic fungi, Indonesia

COMPARATIVE EVALUATION OF KETOPROFEN CREAM WITH DICLOFENAC AND PIROXICAM CREAM IN PATIENTS WITH RHEUMATOID ARTHRITIS DISORDERS: Muhammad Razi Ullah Khan; Saeed Ur Rashid Nazir; Musaddique Hussain
Indonesian Journal of Pharmacy Vol 26 No 1, 2015
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Non steroidal Anti- inflammatory drugs have their origin as the derivatives of plants, which were observed to have their therapeutic effects in different disease states. They have the advantage of local action without developing central adverse effects and cognitive impairments. Side effects have been well described, although partly neglected. Topical delivery of NSAID has its therapeutic applications in management of pain and inflammation in Rheumatoid arthritis patients. Rheumatoid arthritis is a chronic systemic inflammatory disorder that may affect many tissues and organs but principally attacks the synovial joints. It can be disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated. The aim of the present investigation was to compare the Ketoprofen cream with Diclofenac and Piroxicam cream in a group of volunteers suffered from Rheumatoid arthritis and to compare the efficacy of these creams in reduction of inflammation. This single blind comparative study was done to determine the efficacy, tolerability and acceptability of topical application of Ketoprofen cream (1%w/w) vs diclofenac cream (1%w/w) and piroxicam cream (0.5%w/w) in Rheumatoid arthritis patients. In this study, one hundred and twenty five volunteers suffering with acute Rheumatoid arthritis and age group between 40-70 years were analyzed for assessing the intensity of pain and anti-inflammatory effects of these three creams. The study revealed that Ketoprofen cream provides a good level of pain relief removes swelling and tenderness and improves the functional impairment, without the systemic adverse events associated with oral NSAIDs.Key Words: Cream, Diclofenac, Ketoprofen, Piroxicam, Rheumatoid arthritis

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