Advanced Materials Research Vol. 1060

Abstract: DNA Topoisomerase I is an enzyme, which is involved in DNA replication, transcription and chromosome segregation in cellular processes. Inhibitors of Topoisomerase I are designed to interrupt DNA replication in cancer cells, resulting in cell death. The goal of these studies was to identify structural features necessary for increasing inhibitory effect of Topoisomerase I and further use these features for designing novel anticancer agents. 3D-QSAR method was performed for 15 chromone derivatives using Comparative Molecular Similarity Indices Analysis (CoMSIA) method. The best CoMSIA model was obtained from AM1 geometry optimization and align database alignment. The satisfactory CoMSIA model based on steric, electrostatic, hydrophobic and hydrogen bond acceptor fields gave a leave-one-out cross-validation q² = 0.753 and a non-cross-validation r2 = 0.987. Therefore, the resulting contour maps produced by the best CoMSIA models could be used to understand the important structural features responsible for the design and development of new highly active topoisomerase I inhibitors.

Abstract: The aim of study was to determine the effect of glycerol on the properties of tapioca starch films. The films containing various amounts of glycerol (0-30 %w/w) were prepared by casting method. Texture analyzer, x-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) were used to comparatively characterize the films. The result indicated that mechanical properties were depended on amount of incorporated glycerol. The films containing 0-10 %w/w of glycerol showed brittle characteristic while those containing 20-30 %w/w demonstrated elastic film, suggesting the plasticization effect of glycerol. As indicated by x-ray diffractometry, the crystallinity was increased as increasing percentage of glycerol. The 3D structural change after incorporation of glycerol in polymer chain of starch might affect the properties of films. However, the FTIR spectra did not show clear interaction between glycerol and starch. The physical entrapment of glycerol in amylose chain might be a possible explanation for the results.

Abstract: The evaluation of PEG as a gelation solvent for an organogel based on β-cyclodextrin (β-CyD) was investigated using principal component analysis (PCA). The test tube tilting method was performed to examine the gel formation experimentally. The important descriptors used in the PCA included the Hansen partial solubility parameters. LogP may be able to be used as an additional descriptor for this system. According to PCA analysis, PEG was in a cluster of gelation solvents. Subsequently, various PEG liquid state grades were tested for their ability to gel the system and PEG400 was found to be able to produce a gel. This verifies that PCA can be successfully used to evaluate the role of PEG. Accordingly, this PCA method may be an effective tool to evaluate the role of any solvent for other low molecular weight gelators (LMWGs). Afterwards, the optimal components in the system were explored, and it was found to be 0.1M β-CyD, 0.5M K₂CO₃ in PEG400. Based on WAXS, the gel fiber of this organogel was demonstrated to be amorphous. This forming organogel will be further characterized in details and investigated for use in a drug delivery system.

Abstract: Chemical composition and swelling behaviour of crude tamarind gum from Tamarindus indica seed were observed and compared with modified gums as used carboxymethylation reaction. The condition of carboxymethylation at 70°C for 60 min of reaction time and methanol as solvent media was used. Different mole ratios of sodium hydroxide to monochloroacetic acid (n_NaOH/n_MCA) from 1 to 2.78 were studied and then its degree of substitution (DS) of both crude and carboxymethylated tamarind gums was also determined and compared. Then the swelling property of all samples was evaluated by using gravimetric technique (weight difference between dry and wet polymer). The results from swelling test showed that crude tamarind gum behaved low swelling while carboxymethylated tamarind gums showed high swelling profiles, ranged from 17 to 81% during 60 min. This is a preliminary assessment to expressing pharmaceutical application possibility of tamarind gum as disintegrant, diluent and drug release controlling agent.

Abstract: The aim of this study was to apply contact angle method for the determination of the pH solubility profile of bleached shellac film. Various pH of buffer solution was dropped on the bleached shellac film and drop shape analysis was investigated. The changes in the contact angle and contact line were recorded during 10-min measurement. The graphs of change in slope –obtained from plot between contact angle and time-and % change in contact line were plotted against various pH. The results illustrated the slight change in slope and % change in contact line at low pH while the significant change was reported at high pH. The results were in agreement with % dissolved film at various pH. The bleached shellac film started to dissolve at pH 7. The higher % dissolved film was obtained at pH 8 and 9 and at pH 10 was completely dissolved. Therefore, the contact angle method by the drop shape analysis, a simple method and less solvent used, can be an indicator for determination of pH solubility profile of bleached shellac. The result obtained could then be applied to the other substances.

Abstract: The aim of the study was to develop neural network model to predict the yield obtained from ultrasound-assisted anti-solvent crystallization of ibuprofen in terms of formulation and processing factors. The different factors of anti-solvent crystallization method, such as type of additive, concentration of additive, sonication time and harvesting time, were used as independent variables. The ibuprofen yield was used as response variable. The correlation between independent and response variables was investigated using feed forward-back propagation neural networks. The goodness of fit test and predictability were used for optimization of in silico models. The results revealed that the type of polyethylene glycol (PEG) was a critical factor that affected the response variable in different patterns. The best artificial neural networks (ANNs) model with a configuration of 3-4-1 for input, hidden, and output layers gave the r² of 0.7067 and 0.8729 and the root mean square error of 0.3693 and 0.2667 for the model using PEG 400 and PEG 4000, respectively. The predictive ability of these models was validated by a set of 4 formulations that were not included in the training set. The predicted and experimental of ibuprofen yields were correlated.

Abstract: Solvent miscibility is an important parameter for dosage form design, especially for liquid preparations. The purpose of this study was to investigate the polarity change of coconut oil (CO) after modification by glycerolysis and its consequence on solvent miscibility. Coconut oil and its modified form were separately mixed with various solvents which had different dielectric constant and then determined for their miscibility. The thin layer chromatography (TLC) was also used to clarify the composition of coconut oil and its modified form. The result indicated that coconut oil and modified coconut oil (MCO) were miscible with low polarity solvent having the dielectric constant from 1.94 to 21.5 (from hexane to acetone) and were immiscible with high polarity solvents possessing the dielectric constant over 42.5. However, MCO demonstrated miscibility with ethanol, propylene glycol and methanol (dielectric constant 24.5, 32.1, 32.7) while coconut oil did not compatible with those solvents. The result suggested the polarity increment of MCO after glycerolysis. The presence of high polar compounds, including monolaurin and lauric acid in MCO was later clarified by TLC. In conclusion, the knowledge gained from this research may provide the preliminary data for formulation of MCO into suitable liquid dosage form in the near future.

Abstract: The aim of this study was to compare the in vitro binding of bile salts by coconut fiber, a by-product of coconut milk extraction. The raw coconut fiber was processed by different methods before binding test, that is, sieving, pulverizing in mortar, grinding by a dry grinder, digesting with 0.1 N hydrochloric acid (HCl), grinding by a dry grinder and then digesting with 0.1 N HCl. The resultant coconut fiber was sieved to obtain the particle size ranged from 250 to 600 μm. Various bile salts, i.e., sodium deoxycholate, sodium cholate and sodium taurocholate, were individually tested and analyzed by high performance liquid chromatography. The results showed that sodium deoxycholate was bound by sieved coconut fiber (9.64%), mortar-ground coconut fiber (12.91%), grinder-ground coconut fiber (28.31%), acid-digested coconut fiber (41.14%), and grinder-ground and acid-digested coconut fiber (37.54%). Similar results were obtained when sodium cholate and sodium taurocholate were tested but to a lesser extent. It can be concluded from these results that coconut fiber may have potential application as a cholesterol-reducing agent.

Abstract: The objectives of research were to synthesize N-benzyl chitosan and to investigate N-benzyl chitosan on the properties of in situ forming gel such as viscosity, syringeability, drug release and antimicrobial activity against Porphyromonas gingivalis. N-benzyl chitosan was synthesized and determined by FTIR. The increased amount of N-benzyl chitosan apparently increased the viscosity and syringeability of this system. N-benzyl chitosan gel could prolong the release of doxycycline hyclate and showed the antimicrobial activity against Porphyromonas gingivalis. N-benzyl chitosan systems could be delivered from syringe through needle for periodontitis treatment.

Abstract: This study aims to estimate simultaneously metformin hydrochloride (MET) and glyburide (GLY) in a multicomponent tablets dosage form by spectrophotometric method using chemometric approaches such as principal component regression (PCR) and partial least-squares regression (PLS). Because of highly overlapped in UV spectra and difference proportions of two active ingredients, the conventional univariate calibration methods was not allowed without previous separation. The linearity ranges used to construct the calibration matrix were selected in the ranges from 40.00 to 200.00 mg L^-1 for MET and from 1.00 to 10.00 mg L^-1 for GLY. The absorbances were measured in the wavelength range of 200-400 nm, using ethanol as solvent. The resulting UV spectra were subjected to PCR and PLS algorithms and the optimum numbers of principal components (PCs) were selected according to prediction residual error sum of squares (PRESS) values of leave-one out cross-validation. The number of PCs for MET and GLY were found to be 5, 3 by PCR and 5, 3 by PLS, respectively. A set of synthetic mixtures was employed to verify the models and the performance of the models were shown in the values of the root mean square error in prediction (RMSEP). RMSEP values of MET and GLY were 1.806, 0.256 for PCR and 1.802, 0.185 for PLS, respectively. The suitable calibration models were applied to the analysis of these compounds in pharmaceutical formulation.