Slamet Ibrahim

A selective distance-based paper analytical device for copper(II) determination using a porphyrin derivative

Meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin sulfonate (TDMPzP), a water-soluble porphyrin derivative, was synthesized and used as a colorimetric reagent for Cu2+ detection on a microfluidic paper-based analytical device (µPAD) using distance-based quantification. TDMPzP showed a high selectivity for Cu2+ detection in aqueous solutions. When Cu2+ was added to the TDMPzP under acidic conditions, a color change from green to a pink was observed by the naked eye. Under optimized conditions, the application of this system to a distance-based μPAD exhibited good analytical response. The presence of common metal ions (Al3+, Fe3+, Mg2+, Co2+, Mn2+, Zn2+, Pb2+, Cd2+, Sn2+, and Ni2+) did not interfere with Cu2+ detection within reasonable tolerance ratios. The lowest concentration of copper that could be measured was 1mgL-1 (1ppm) which meets the requirements for drinking water contamination regulations from the US Environmental Protection Agency (EPA) and World Health Organization (WHO) guidelines for drinking water. Real drinking water samples were analyzed to confirm the practical application of this system and the results showed good agreement with ICP-MS data. This distance-based µPAD based on TDMPzP for Cu2+ detection is convenient and effective for real-time drinking water analysis.

Zwitterionic cocrystal of diclofenac and l-proline: Structure determination, solubility, kinetics of cocrystallization, and stability study

&NA; In recent decades, the design of cocrystals has developed significantly due to the unique characteristics and advantages of cocrystals, which help to improve the physicochemical properties of drugs, especially solubility. Zwitterions are attractive and interesting co‐formers. However, the physicochemical properties of cocrystals with zwitterionic co‐formers, i.e. zwitterionic cocrystals, have not been adequately evaluated. In this study, solid‐state characterization of a newly developed zwitterionic cocrystal of diclofenac (DFA), a non‐steroidal anti‐inflammatory drug, and the amino acid l‐proline (PRO) was performed using Fourier‐transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction (PXRD) analyses. In addition, the crystal structure of the cocrystal (DFA‐PRO) was determined by single‐crystal X‐ray diffraction analysis, after which the zwitterionic structure was confirmed. The cocrystallization during co‐grinding, which was investigated by PXRD, followed first‐order kinetics. Furthermore, the solubility of the zwitterionic cocrystals was 7.5‐times higher than that of the DFA crystals. The results indicate that the cocrystal is stable under ambient conditions; however, it hydrates and transforms into a mixture of l‐proline monohydrate crystals and DFA crystals under conditions of high humidity. Graphical abstract Figure. No caption available.

HYDRATE TRANSFORMATION STUDY OF FLUOROQUINOLONE ANTIBIOTICS USING FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR)

Objective: There are many successful products on the market which are the culmination of the self-micro-emulsification lipid technology applications. Despite the importance of lipid-based formulations, these systems have some limitations including; stability, complexity during large scale manufacturing process and limited dosage forms to such as soft gelatin capsule. In order to overcome these limitations, the prospect of converting self-micro-emulsifying drug delivery systems (SMEDDS) into tablet dosage form was investigated in this study. Methods: A self-micro-emulsifying oil formulation representing type III A lipid class composed of glycerox 767HC/croduret 40 ss at ratios of (80/20) was converted into solid SMEDDS using solid carrier adsorption method. Powder blends containing magnesium trisilicate hydrate (MTSH) or magnesium lluminum silicate (MAS) at various oil loading factors were mixed with MCC with and without various binders and compressed into tablets using a fixed loading force of approximately of 5 KN. Hardness profiles of these oil loaded tablets were then analyzed. Results: Powder compacts which contained MTSH with and without SMEDDS oil had shown relatively better compaction properties than MAS. Adding SMEDDS oil solution to either MTSH or MAS at ratios of 1:9 has relatively reduced tablets hardness by almost 2 or 4 folds, respectively. Conclusion: Progressive inclusion of increasing amounts of SMEDDS oil solution adsorbed unto the solid carrier has incurred a further reduction in the hardness of SMEDDS tablets. It appears that manufacturing of tablet SMEDDS can only be attainable for highly potent drugs as minimal amounts of oil solution added to the powder blends can adversely affect the mechanical strength of compressed tablet.

Determination of ligand position in aspartic proteases by correlating tanimoto coefficient and binding affinity with root mean square deviation

The objective of this study was to develop and validate of Structure-Based Virtual Screening (SBVS) protocol which was used to select the best pose of inhibitor-aspartic protease complex interaction in the active sites of HIV-1 protease, plasmepsin I, II, and IV. Retrospective validation was performed on enhanced dataset of ligands and decoys (DUD-E) for HIV-1 protease. The crystal structures 1XL2, 3QS1, 1SME, and 1LS5 were obtained from Protein Data Bank. The protocol was then challenged to re-dock the ligands to its origin places in the active sites by correlating Tanimoto coefficient (Tc) and binding affinity (Ei) with Root Mean Square Deviation (RMSD). Enrichment factor at 1% false positives (EF1%) values for Tc and Ei were 18.26 and 9.03, respectively, while the Area Under Curve (AUC) values for Tc and Ei were 76.84 and 60.95. The SBVS protocol was validand showed better virtual screening qualities in ligand identification for HIV-1 protease compared to the originalprotocol accompanying the release of DUD-E and showed its ability to reproduce the co-crystal pose in the HIV1 protease, plasmepsin I,II,and IV to its origin places in the active sites.

Formation and Characterization of Mefenamic acid-Nicotinamide Cocrystal during Co-milling Based on X-ray Powder Diffraction Analysis -

Article history: Received on: 11/05/2016 Revised on: 30/06/2016 Accepted on: 16/08/2016 Available online: 29/10/2016 Mefenamic acid (MFA) and Nicotinamide (NIC) cocrystal formation in co-milling treatment was investigated by x-ray powder diffractometry (XRPD). Two polymorphic form of Mefenamic acid (MFA form I and MFA form II) were used to form a cocrystal with nicotinamide. Co-milling treatment was carried out at room temperature in a 1:2 molar ratio of MFA and NIC for various times up to 60 min. Samples were analyzed by XRPD. The XRPD showed that MFA form I and MFA form II formed cocrystal with NIC in the same diffractograms pattern. There was no intermediate amorphous form during milling process. The cocrystal formation mechanism was predicted via intermediate eutectic mixtures. The cocrystal formation from MFA form II (15 min) was faster than from MFA form I (45 min) which may explained by variations unit cell dimensions of MFA form I and MFA form II and also the polymorphic transformation of MFA form I.

Antihyperuricemic Effect of Ethanol Extract of Snake Fruit (Salacca edulis Reinw.) var. Bongkok on Wistar Male Rat

The aim of the study was to investigate antihyperuricemic effect of snake fruit (Salacca edulis Reinw.) var. Bongkok Wistar male rates. Antihyperuricemic investigation on Wistar male rats showed that administration of ethanol extract at doses of 200 mg/kg bw decreased serum uric acid level significantly compared to control group at hour 6 and 7 (P < 0.05) after inducing with potassium oxonate intraperitoneally simultaneously with uric acid orally. Whereas, administration of ethanol extract at doses of 100 mg/kg bw did not decrease serum uric acid level significantly different compared to control group at hour 6 and 7 (P < 0.05). Determination of uric acid level in urine, administration of ethanol extract at a dose of 200 mg/kg bw, or probenecid as a standard drug, at a dose of 45 mg/kg bw increased excretion of urine uric acid level significantly different compared to control group in day of 7 (P < 0.05) after inducing with potassium oxonate intraperitoneally simultaneously with uric acid orally. However, increase of uric acid excretion by ethanol extract was lower compared to that of probenecid at a dose of 45 mg/kg bw. Mechanism of action of the ethanol extract as an antihyperuricemia has been proposed by inhibition of xanthine oxidase and finally decreased the synthesis of uric acid and increased the excretion of urine uric acid level.

Synthesis and Characterization Molecularly Imprinted Polymers for Analysis of Dimethylamylamine Using Acrylamide as Monomer Functional

A selective separation techniques with Molecularly Imprinted Polymer (MIP) for High-Performance Liquid Chromatography (HPLC) has been developed for the assay of Dimethylamylamine (DMAA) doping compounds. Molecular imprinted polymer (MIP) is a technique to produce a polymer having the cavity due to the disposal of the templates, in which the cavity serves to recognize the molecules of the same size, structure, chemical and physical properties. The selectivity and affinity of the templates itself will increase, while the concentration value is increasing. MIP is made by DMAA as template, acrylamide as functional monomer, ethylene glycol dimethacrylate (EGDMA) as cross linking, azobisisobutyronitrile (AIBN) as the initiator and chloroform as a porogen solvent; using bulk method. The aim of research are conduct the MIP for the DMAA compound analysis, then the formed MIP is characterized by using Fourier Transform Infra Red (FTIR) and Scanning Electron Microscopy (SEM) to find out the polymer complexes formed and the morphological form of the MIP. The MIP formed then was analyzed by using High-Performance Liquid Chromatography (HPLC) to know the amount of the DMAA, the adsorption capacity, and the adsorption condition found in the MIP. The result of analysis on the content of DMAA in the MIP by using UV-Vis Spectrophotometer is 1.957 mg. Scanning Electron Microscopy (SEM) shows that the MIP has irregular and rough morphological structure; while the NIP has irregular morphology structures and smooth surfaces shape

Development and Validation of Content Uniformity Analytical Procedure of Glipizide Extended Release Tablet

Glipizide is an oral anti-diabetic drug which belongs to the class of second-generation sulfonyl-ureas. The matrices of an extended release (ER) dosage form often bring some problems in the analytical work, so it needs suitable procedure for extraction and separation. In this experiment, the glipizide ERs were prepared for a quantitative analysis by solid phase extraction (SPE) using HLB sorbent and dissolved in the mobile phase. Next, the sample preparations were analyzed with a Reversed Phase High-Performance Liquid Chromatography (RP-HPLC). The good separation was achieved on an HPLC YMC Triart C18 (150 x 4.6 mm, ID S-5 µm 12nm) column. The 0.1M buffer sodium dihydrogen phosphate mono base pH 6.00 ± 0.05 - methanol in the ratio 55:45 was used as the mobile phase, with flow rate of 1.0 mL/min, and column temperature was maintained at 30oC. The eluted compound was monitored at a wavelength of 225 nm using an UV detector, within a run time of 23 min. Analytical procedure development yielded a good linearity at a range concentration 0.01 – 0.07 mg/mL with its calibration curve: y = 58985.35x + 13.88 and the correlation coefficient of r = 0.9995. The limit of detection (LOD) was determined as 0.0025 mg/mL, meanwhile the limit of quantitation (LOQ) was 0.0075 mg/mL. The % RSD the inter-day precision was obtained 0.90%, 1.40% and 0.86%, while the % RSD the intra-day precision was obtained 1.23%. The mean recovery of glipizide placebo spike was 100.68%. It was concluded that the procedure is valid and can be applied for determination content uniformity of glipizide in the ER tablet dosage forms.

O-desmethylquinine as a Cyclooxygenase-2 (COX-2) Inhibitors Using AutoDock Vina

Computational approach was employed to evaluate the biological activity of novel cyclooxygenase-2 COX-2 inhibitor, O-desmethylquinine, in comparison to quinine as common inhibitor which can also be used an agent of antipyretic, antimalaria, analgesic and antiinflamation. The molecular models of the compound were constructed and optimized with the density function theory with at the B3LYP/6-31G (d,p) level using Gaussian 09 program. Molecular docking studies of the compounds were done to obtain the COX-2 complex structures and their binding energies were analyzed using the AutoDock Vina. The results of docking of the two ligands were comparable and cannot be differentiated from the energy scoring function with AutoDock Vina.

The Cold Contact Method as a Simple Drug Interaction Detection System

The physical interaction between 2 substances frequently occurs along the mixing and manufacturing of solid drug dosage forms. The physical interaction is generally based on coarrangement of crystal lattice of drug combination. The cold contact method has been developed as a simple technique to detect physical interaction between 2 drugs. This method is performed by observing new habits of cocrystal that appear on contact area of crystallization by polarization microscope and characterize this cocrystal behavior by melting point determination. Has been evaluated by DSC, this method is proved suitable to identify eutecticum interaction of pseudoephedrine HCl-acetaminophen, peritecticum interaction of methampyrone-phenylbutazon, and solid solution interaction of amoxicillin-clavulanate, respectively.