• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.201-205
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• 2009

Triglyceride solid lipid with medium chain fatty acid, tricaprin (TC), was used as a core matrix of lipid nanoparticles (LN) to solubilize water-insoluble paclitaxel and enhance the stability of nanoparticles by immobilization of incorporated drug in the solid core during storage at low temperature. In the present study, TC-LN containing paclitaxel was prepared by hot melt homogenization method using TC as a core lipid and phospholipids as stabilizers. The particle size of TC-LN containing paclitaxel was less than 200 nm and its zeta potential was around -40 mV. Calorimetric analysis showed TC core could be solidified by freezing and thawing in the manufacturing process in which the hot dispersion should be prepared at elevated temperature and subsequently cooled to obtain solid lipid nanoparticles. The melting transition of TC core was observed at $27.5^{\circ}C$, which was lower than melting point of TC bulk. The particle size of TC-LN remained unchanged when kept at $4^{\circ}C$. Paclitaxel containing TC-LN showed comparable anticancer activity to the Cremophore ELbased paclitaxel formulation against human ovarian (OVCAR-3) and breast (MCF-7) cancer cell lines. Thus, lipid nanoparticles with medium chain solid lipid may have a potential as alternative delivery system for parenteral administration of paclitaxel.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.75-82
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• 2011

LB71350 is an HIV protease inhibitor with poor aqueous solubility and extensive first pass effect. The purpose of the present study was to test the feasibility of solid dosage form of LB71350 with improved bioavailability utilizing solid dispersion. Three different compositions with varying ratio of (LB71350: Gelucire 44/14: Tween 20) were studied. Capsule filling of these solid dispersion compositions was tested using a semi-automatic capsule filling system. Oral bioavailability in dog was tested. Chemical and physical stability at 4, 25 and $40^{\circ}C$ was monitored by HPLC assay, dissolution test, powder XRD and microscopy. The capsule filling system yielded uniform products of drug loading up to 10%. Oral bioavailability in dog was improved compared to the aqueous suspension of crystalline LB71350. Capsules were chemically stable for up to 6 months at $40^{\circ}C$. However, there were temperature and composition dependent physical changes. Decrease in dissolution rates after storage at $40^{\circ}C$ was due to the polymorphic change. In conclusion, manufacturing process, bioavailability, and physico-chemical stability have been considered to propose a solid dispersion capsule formulation for the HIV protease inhibitor with poor physico-chemical properties. A new less soluble crystalline form identified during the physical stability test warrants further study.

• Proceedings of the Computational Structural Engineering Institute Conference
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• 2002.10a
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• pp.583-590
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• 2002

Point collocation method based on the fast derivatives approximation of meshfree shape function is applied to solid mechanics in this study. Enhanced meshfree approximation with approximated derivative of shape function is reviewed, and formulation of linear elastic solid mechanics by point collocation method is presented. It implies that governing equation of solid mechanics with strong form is directly formulated without no numerical integration cells or grid. The regularity of weight function is not required due to a use of approximated derivative, so we propose the exponential type weight function that is discontinuous in first derivative. The convergence and stability of the proposed method is verified by passing the generalized patch test. Also, the efficiency and applicability of the proposed method in solid mechanics is verified by solving types of solid problems. Numerical results show that not only a use of proposed weight function leads lower error and higher convergence rate than that of the conventional weight functions, but also the improved collocation method with derivative approximation enables to compute the derivatives of shape function very fast and accurately enough to replace the classical direct derivative calculation.

• Journal of Powder Materials
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• v.30 no.6
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• pp.493-501
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• 2023

This study aimed to develop a solid self-nanoemulsifying drug delivery system (solid-SNEDDS) to enhance the formulation of ketoconazole (KTZ), a BCS Class II drug with poor solubility. Ketoconazole, which is insoluble above pH 3, requires solubilization for effective delivery. This SNEDDS comprises oil, surfactant, and co-surfactant, which spontaneously emulsify in the gastrointestinal tract environment to form nanoemulsions with droplet sizes less than 100 nm. The optimal SNE-vehicle composition of oleic acid, TPGS, and PEG 400 at a 10:80:10 weight ratio was determined based on the smallest droplet size achieved. This composition was used to prepare liquid SNEDDS containing ketoconazole. The droplet size and polydispersity index (PDI) of the resulting liquid SNEDDS were analyzed. Subsequently, solid-SNEDDS was fabricated using a spray-drying method with solidifying carriers such as silicon dioxide, crospovidone, and magnesium alumetasilicate. The physicochemical properties of the solid-SNEDDS were characterized by scanning electron microscopy and powder X-ray diffraction, and its solubility, droplet size, and PDI were evaluated. In particular, the solid-SNEDDS containing ketoconazole and crospovidone in a 2:1 weight ratio exhibited significantly enhanced solubility, highlighting its potential for improved medication adherence and dissolution rates.

• Journal of Pharmaceutical Investigation
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• v.22 no.4
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• pp.281-287
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• 1992

Omeprazole (OMZ) is very unstable in acidic solution, which selectively inhibit the release of the gastric juice in the gastric mucosa, In order to stabilize (OMZ) in oral solid dosage form, the enteric-coated microcapsules and compression-coated OMZ tablets containing lysine or arginine as stabilizer were prepared and their dissolution and stability test were performed. The haif life of OMZ microcapsules containing arginine was 194 days at $30^{\circ}C$ and OMZ was completely released in 60 min. The half-lives of enteric coated and non-coated compression-coated OMZ tablets with lysine were 292 and 95 days at $30^{\circ}C$, respectively. The half-lives of enteric coated and non-coated compression-coated tablets with arginine were 1752 and 293 days at $30^{\circ}C$, respectively, and OMZ were released completely in 20 min in the 2nd fluid of K.P.VI. Consequently, the enteric-coated compression-coated OMZ tablets with arginine as stabilizer provided a good formulation for oral solid dosage form.

• Structural Engineering and Mechanics
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• v.36 no.5
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• pp.575-598
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• 2010

The shape and size of the plastic zone around the crack tip are analyzed under pure mode I, pure mode II and mixed mode (I+II) loading for small scale yielding and for both plane stress and plane strain conditions. A new analytical formulation is presented to determine the radius of the plastic zone in a non-dimensional form. In particular, the effect of T-stress on the plastic zone around the crack tip is studied. The results of this investigation indicate that the stress field with a T-stress always yields a larger plastic zone than the field without a T-stress. It is found that under predominantly mode I loading, the effect of a negative T-stress on the size of the plastic zone is more dramatic than a positive T-stress. However, when mode II portion of loading is dominating the effect of both positive and negative T-stresses on the size of the plastic zone is almost equal. For validating the analytical results, several finite element analyses were performed. It is shown that the results obtained by the proposed analytical formulation are in very good agreements with those obtained from the finite element analyses.

• Advances in aircraft and spacecraft science
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• v.4 no.3
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• pp.219-235
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• 2017

The large container ships and fast patrol boats are complex marine structures. Therefore, their global mechanical behaviour has long been modeled mostly by refined beam theories. Important issues of cross section warping and bending-torsion coupling have been addressed by introducing special functions in these theories with inherent assumptions and thus compromising their robustness. The 3D solid Finite Element (FE) models, on the other hand, are accurate enough but pose high computational cost. In this work, different marine vessel structures have been analysed using the well-known Carrera Unified Formulation (CUF). According to CUF, the governing equations (and consequently the finite element arrays) are written in terms of fundamental nuclei that do not depend on the problem characteristics and the approximation order. Thus, refined models can be developed in an automatic manner. In the present work, a particular class of 1D CUF models that was initially devised for the analysis of aircraft structures has been employed for the analysis of marine structures. This class, which was called Component-Wise (CW), allows one to model complex 3D features, such as inclined hull walls, floors and girders in the form of components. Realistic ship geometries were used to demonstrate the efficacy of the CUF approach. With the same level of accuracy achieved, 1D CUF beam elements require far less number of Degrees of Freedom (DoFs) compared to a 3D solid FE solution.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.179-184
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• 2011

This study aimed to confirm the effect of molecular weight (MW) in solid dispersion of carvedilol with poly-vinylpyrrolidone (PVP) of various MW. Solid dispersion of carvedilol with PVP was prepared by spray-drying method. Scanning electron microscopy (SEM) was used to analyze the surface of solid dispersion samples. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze the crystalline of solid dispersion. Fourier transform infrared spectroscopy (FT-IR) was used to analyze the change of chemical structure characteristic of solid dispersion. DSC and XRD show that drug crystalline was changed. FT-IR revealed that chemical structure of solid dispersion comparing the chemical structure of drug was changed. The dissolution studies of solid dispersion presented at simulated gastric juice (pH 1.2). The dissolution rate of solid dispersion was dramatically enhanced than pure drug and the MW of PVP has an effect on the release property of carvedilol in solid dispersion. In conclusion, the present study has confirmed the effect of MW of PVP on release property of solid dispersion formulation of carvedilol with PVP.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.151-160
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• 2001

The purpose of this study is to investigate the interaction of progesterone with various cyclodextrins (CDs) in the aqueous solution and in solid state, and finally to formulate a parenteral aqueous formulation. CDs used were ${\alpha}-$, ${\beta}-$, and ${\gamma}-CD$, $2-hydroxypropyl-{\beta}-CD$ (HPCD), sulfobutyl $ether-{\beta}-CD$ (SBCD), $dimethyl-{\beta}-CD$ (DMCD) and $trimethyl-{\beta}-CD$ (TMCD). The solubility studies of progesterone were performed in the presence of various CDs as a function of concentration or temperature. The solubility of progesterone increased in the rank order of ${\alpha}-CD$ < ${\beta}-CD$ < ${\gamma}-CD$ < TMCD$ < HPCD < DMCD < SBCD. Addition of SBCD (200 mg/ml) in water increased the aqueous solubility $(9.36\;{\mu}g/ml)$ about 3,200 times, and lowering the temperature facilitated the solubilization of progesterone. However, the addition of HPCD and SBCD in 20:80 (v/v) polyethylene glycol 300-water and propylene glycol-water cosolvents markedly decreased the solubility of progesterone, compared with solubilizing effects in water. Physical mixtures and solid dispersions of progesterone with HPCD or SBCD were prepared, and evaluated by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), near IR spectroscopy and dissolution studies. By DSC and IR studies, it was found that progesterone was dispersed in HPCD in monotectic state and dissolved rapidly from both solid dispersions. Based on solubility studies, new aqueous progesterone fonnulations (5 mg/ml) containing SBCD (200 mg/ml) could be prepared and did not form precipitates even after 2 months at $4^{\circ}C$. The solution was transparent when mixed with normal saline and 5% dextrose injection at 1: 1, 1:10 and 1:20 (v/v) even after 7 days. Permeation rates of progesterone through a cellulose membrane from 20% PEG 300 solution $(50\;{\mu}g/ml)$ containing HPCD or SBCD were compared with oily formulation. Permeation of progesterone from oily formulation did not occur up to 8 hr, but aqueous formulations showed fast permeation rates from early stage of permeation study. The addition of HPCD or SBCD retarded the permeation rates of progesterone with the increase of CD concentrations, suggesting the possibility of a controlled absorption from the site administered intramuscularly. These results demonstrate that it is feasible to develop a new progesterone parenteral aqueous injection (5 mg/ml) using SBCD.

• Structural Engineering and Mechanics
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• v.11 no.3
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• pp.325-340
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• 2001

This paper addresses an efficient modification method that eliminates the undesirable effects of strains due to various non-conforming modes so that the non-conforming element can pass the patch test unconditionally. The scheme is incorporated in the element formulation to establish new types of non-conforming hexahedral elements designated as NHx and NVHx for the regular element and variable node element, respectively. Non-conforming displacement modes are selectively added to the ordinary (conforming) element displacement assumptions to improve the bending behavior of the distorted solid element. To verify the validation of proposed direct modification method and the improvement of element behavior, several numerical tests are carried out. Test results show that the proposed method is effective and its applications to non-conforming solid elements guarantee for the element to pass the patch test.