• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1587-1592
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• 2011

The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble drug in human body, using a solid dispersion technique (hot melt extrusion). The solid dispersion was prepared by cooling the hot melt of the drug in the carrier (Vitamin E TPGS and PVP). The dissolution rate of formulation 1 from a novel formulation prepared by solid dispersion technique was equal to release of formulation 6 (40% of eprosartan mesylate is in contrast to teveten$^{(R)}$) within 60 min (Table 1). The oral bioavailability of new eprosartan mesylate tablet having vitamin E TPGS and PVP K29 was tested on rats and dogs. Of the absorption enhancer and polymer tested, vitamin E TPGS and PVP K29, resulted in the greatest increases of AUC in animals (about 2.5-fold increase in rat and dog). When eprosartan mesylate was mixed with the absorption enhancer and polymer in a ratio of 2.94:2:1, vitamin E TPGS and PVP K29 improved eprosartan mesylate bioavailability significantly compared with the conventional immediate release (IR) tablet Teveten$^{(R)}$ (formulation 7). These results show that solid dispersion using vitamin E TPGS and PVP K29 is a promising approach for developing eprosartan mesylate drug products.

• Coupled systems mechanics
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• v.11 no.5
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• pp.439-458
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• 2022

Over-coating is one of the most popular engineering practices to strengthen Reinforced Concrete (RC) structures, due to the relative quickness and ease of construction. It consists of an external coat bonded to the outer surface of the structural RC element, either by the use of chemical adhesives, mechanical anchor bolts or simply mortar injection. In contrast to these constructive advantages, the numerical estimation of the bearing capacity of the strengthened reinforced concrete element is still complicated, not only for the complexity of modelling a flexible membrane or plate attached to a quasi-rigid solid, but also for the difficulties that raise of simulating any potential delamination between both materials. For these reasons, the standard engineering calculations used in the practice remain very approximated and clumsy. In this work, we propose the formulation of a new 2D solid-layer finite element capable to link a solid body with a flexible thin layer, as it were the "skin" of the body, allowing the potential delamination between both materials. In numerical terms, this "skin" element is intended to work as a transitional region between a solid body (modelled with a classical formulation of a standard quadrilateral four-nodes element) and a flexible coat layer (modelled with cubic beam element), dealing with the incompatibility of Degrees-Of-Freedom between them (two DOF for the solid and three DOF for the beam). The aim of the solid-layer element is to simplify the mesh construction of the strengthened RC element being aware of two aspects: a) to prevent the inappropriate use of very small solid elements to simulate the coat; b) to improve the numerical estimation of the real bearing capacity of the strengthened element when the coat is attached or detached from the solid body.

• Coupled systems mechanics
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• v.12 no.6
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• pp.481-501
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• 2023

Over-coating is one of the most popular engineering practices to strengthen Reinforced Concrete (RC) structures, due to the relative quickness and ease of construction. It consists of an external coat bonded to the outer surface of the structural RC element, either by the use of chemical adhesives, mechanical anchor bolts or simply mortar injection. In contrast to these constructive advantages, the numerical estimation of the bearing capacity of the strengthened reinforced concrete element is still complicated, not only for the complexity of modelling a flexible membrane or plate attached to a quasi-rigid solid, but also for the difficulties that raise of simulating any potential delamination between both materials. For these reasons, the standard engineering calculations used in the practice remain very approximated and clumsy. In this work, we propose the formulation of a new 2D solid-layer finite element capable to link a solid body with a flexible thin layer, as it were the "skin" of the body, allowing the potential delamination between both materials. In numerical terms, this "skin" element is intended to work as a transitional region between a solid body (modelled with a classical formulation of a standard quadrilateral four-nodes element) and a flexible coat layer (modelled with cubic beam element), dealing with the incompatibility of Degrees-OfFreedom between them (two DOF for the solid and three DOF for the beam). The aim of the solid-layer element is to simplify the mesh construction of the strengthened RC element being aware of two aspects: a) to prevent the inappropriate use of very small solid elements to simulate the coat; b) to improve the numerical estimation of the real bearing capacity of the strengthened element when the coat is attached or detached from the solid body.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.167-172
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• 2001

All-trans retinoic acid (ATRA), vitamin A acid, has been shown to exert anticancer activity in a number of types of cancers, particularly in acute promyelocytic leukaemia (APL). Due to its highly variable bioavailability and induction of its own metabolism after oral treatment, development of parenteral dosage forms are required. However, its poor aqueous solubility and chemical unstability give major drawbacks in parenteral administration. This study was undertaken to investigate a possibility to develop a parenteral formulation of ATRA by employing solid lipid nanoparticle (SLN) as a carrier. By optimizing the production parameters and the composition of SLNs, SLNs with desired mean particle size (<100 nm) as a parenteral dosage form could be produced from trimyristin (as solid lipid), Egg phosphatidylcholine and Tween 80 (as SLN stabilizer). The mean particle size of SLN formulation of ATRA was not changed during storage, suggesting its physical stability. Thermal analysis confirmed that the inner lipid core of SLNs exist at solid state. The mean particle size of ATRA-loaded SLNs was not significantly changed by the lyophilization process. ATRA could be efficiently loaded in SLNs, while maintaining its anticancer activity against HL-60, a well-known APL cell line. Furthermore, by lyophilization, ATRA loaded in SLN could be retained chemically stable during storage. Taken together, our present study demonstrates that physically and chemically stable ATRA formulation adequate for parenteral administration could be obtained by employing SLN technology.

• Journal of Mechanical Science and Technology
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• v.15 no.11
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• pp.1499-1506
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• 2001

Various transition elements are used in general for the effective finite element analysis of complicated mechanical structures. In this paper, a solid-to-beam transition finite element, which can b e used for connecting a C1-continuity beam element to a continuum solid element, is proposed. The shape functions of the transition finite element are derived to meet the compatibility condition, and a transition element equation is formulated by the conventional finite element procedure. In order to show the effectiveness and convergence characteristics of the proposed transition element, numerical tests are performed for various examples. As a result of this study, following conclusions are obtained. (1) The proposed transition element, which meets the compatibility of the primary variables, exhibits excellent accuracy. (2) In case of using the proposed transition element, the number of nodes in the finite element model may be considerably reduced and the model construction becomes more convenient. (3) This formulation method can be applied to the usage of higher order elements.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.267-274
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• 1998

Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of acute and chronic hepatitis. However, its poor solubility in water, $2.5\;{\mu}g/ml$, caused low bioavailability of the drug after its oral administration. In order to increase the dissolution of DDB in gastrointestinal tracts, consequently to increase the bioavailability of the drug, DDB tablet was prepared with solid dispersion of DDB with poloxamer 338 or 407 using a direct compression method. To improve the flowability of the solid dispersion, Aerosil was used as an adsorbent. The effect of formulation variables (poloxamer and Aerosil contents) on the dissolution rate of DDB from tablets was investigated using an analysis of variance. The dissolution rate of DDB from tablets was evaluated with KP II (paddle) method. The dissolution patterns of the drug from the tablet prepared with poloxamer 407 were affected significantly by the contents of poloxamers and Aerosil over the range employed, but those of the drug from the tablet prepared with poloxamer 338 were not. The optimum formulation of the DDB tablet, showed the same dissolution pattern as that of the reference, was obtained after polynomial equations of drug dissolution profiles for each formula were fitted to contour plots. The optimum formulation ratios of DDB:poloxamer 407:Aerosil were 1:2.5:2.5 and 1:5:5.

• Proceedings of the KSME Conference
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• 2000.04b
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• pp.709-714
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• 2000

A splitting method for the direct numerical simulation of solid-liquid mixtures is presented, where a symmetric pressure equation is newly proposed. Through numerical experiment, it is found that the newly proposed splitting method works well with a matrix-free formulation fer some bench mark problems avoiding an erroneous pressure field which appears when using the conventional pressure equation of a splitting method. When deriving a typical pressure equation of a splitting method, the motion of a solid particle has to be approximated by the 'intermediate velocity' instead of treating it as unknowns since it is necessary as a boundary condition. Therefore, the motion of a solid particle is treated in such an explicit way that a particle moves by the known form drag (pressure drag) that is calculated from the pressure equation in the previous step. From the numerical experiment, it was shown that this method gives an erroneous pressure field even for the very small time step size as a particle velocity increases. In this paper, coupling the unknowns of particle velocities in the pressure equation is proposed, where the resulting matrix is reduced to the symmetric one by applying the projector of the combined formulation. It has been tested over some bench mark problems and gives reasonable pressure fields.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.217-225
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• 2011

The aim of this work was to prepare porous osmotic pump tablets for controlled delivery of Aceclofenac. Aceclofenac solid dispersion was prepared to improve the solubility by using the drug - carrier (Mannitol) ratio of 1:1. The osmotic pump tablets were prepared using the solid dispersed product of Aceclofenac. The formulation contains potassium chloride as osmotic agent, cellulose acetate as semipermeable membrane, poly ethylene glycol (PEG 4000) as pore former and sodium lauryl sulphate (SLS) as solubility enhancer. The formulations were designed by the general factors such as osmotic agent and pore former. All formulations were evaluated for various physical parameters and, the in vitro release studies were conducted as per USP. The drug release kinetic studies such as zero order, first order, and Higuchi and Korsmeyer peppas were determined and compared. All the formulations gave more controlled release compared to the marketed tablet studied. Numerical optimization techniques were applied to found out the best formulation by considering the parameter of in vitro drug release kinetics and dissolution profile standards. It was concluded that the porous osmotic pump tablets (F7) composed of Aceclofenac solid dispersion/Potassium chloride/Lactose/Sodium lauryl sulphate/Magnesium Stearate (400/40/95/10/5, mg/tab) and coating composition with Cellulose acetate/ PEG 4000 (60/40 %w/w) is the most satisfactory formulation. The porous osmotic pump tablets provide prolonged, controlled, and gastrointestinal environment-independent drug release.

• Proceedings of the KSME Conference
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• 2000.04a
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• pp.351-356
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• 2000

Various transition elements are generally used for the effective analysis of a complicated mechanical structure. In this paper, a solid-to-beam transition finite element which connects a continuum element and a $c^1-continuity$ beam element each other is proposed. The shape functions of the transition finite elements, which a 8-noded hexahedral solid element fur 3D analysis and a 4-noded quadrilateral plane element fur 2D analysis are connected to a Euler's beam element, are explicitely formulated. In order to show the effectiveness and convergence characteristics of the proposed transition elements. numerical tests are performed for various examples and their results are compared with those obtained by other methods. As the result of this study. following conclusions are obtained: (1)The proposed transition finite elements show the monotonic convergence characteristics because of having used the compatible displacement folds. (2)As being used the transition element in the finite element analysis, the finite element modelings are more convenient and the analysis results are more accurate because of the formulation characteristies of the Euler's beam element.

• Mass Spectrometry Letters
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• v.7 no.3
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• pp.79-83
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• 2016

We prepared solid dispersion formulations of quercetin to enhance its solubility and dissolution rate. Various quercetin-loaded solid dispersion were tested with quercetin, poloxamer 407, and carrier such as hydroxypropyl methyl cellulose (HPMC), polyethylene glycol 8000 (PEG 8000), and polyvinylpyrrolidone K40 (PVP K40) using solvent evaporation and freeze drying methods in terms of both the aqueous solubility and the dissolution rates of quercetin. The solubility of quercetin as its solid dispersion formulations was markedly improved compared with that of quercetin powder. Especially, highest solubility of quercetin was observed when HPMC was used as a carrier. The cumulative dissolution of quercetin within 360 min from solid dispersion composed of quercetin, poloxamer 407, and HPMC was 8.8-fold higher than the dissolution of pure quercetin. The results of powder X-ray diffraction (XRD) and scanning electron microscope (SEM) indicated that quercetin transformed from a crystalline to an amorphous form through the solid dispersion formulation process. These results suggest that the solid dispersion formulation of quercetin with poloxamer 407 and HPMC could be a promising option for enhancing the solubility and dissolution rate of quercetin.