• 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.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.866-874
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• 2005

The objective of this study was to elucidate the feasibility to improve the solubility and bioavailability of poorly water-soluble itraconazole via solid dispersions by using supercritical fluid (SCF). Solid dispersions of itraconazole with hydrophilic polymer, HPMC 2910, were prepared by the aerosol solvent extraction system (ASES) under different process conditions of temperature/pressure. The particle size of solid dispersions ranged from 100 to 500 nm. The equilibrium solubility increased with decrease (15 to 10 MPa) in pressure and increase (40 to $60^{\circ}C$) in temperature. The solid dispersions prepared at $60^{\circ}C$/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at $60^{\circ}C$/10MPa showed approximately 610-fold increase and no endothermic peaks corresponding to pure itraconazole were observed, indicating that itraconazole might be molecularly dispersed in HPMC 2910 in the amorphous form. The amorphous state of itraconazole was confirmed by DSC/XRD data. The pharmacokinetic parameters of the ASES-processed solid dispersions, such as $T_{max},\;C_{max},\;and\;AUC_{0-24h}$ were almost similar to $Sporanox_{\circledR}$ capsule which shows high bioavailability. Hence, it was concluded that the ASES process could be a promising technique to reduce particle size and/or prepare amorphous solid dispersion of drugs in order to improve the solubility and bioavailability of poorly water-soluble drugs.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.19 no.3
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• pp.353-366
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• 2021

The solubilities of different multicomponent lanthanide oxide (Ln₂O₃) solid solutions including binary (Ln₁ and Ln₂ = La, Nd, Eu, or Tm), ternary (Ln₁, Ln₂, and Ln₃ = La, Nd, Eu, or Tm), and higher systems (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were studied after aging for four weeks at 60℃. Our recent study revealed that the phase transformations in binary ((La, Nd) and (La, Eu)) and ternary (La, Nd, Eu) systems are responsible for the formation of (La, Nd)(OH)₃, (La, Eu)(OH)₃, and (La, Nd, Eu)(OH)₃ solid solutions, respectively. The variations in the mole fractions of La³⁺, Nd³⁺, and Eu³⁺ in the sample solutions of these hydroxide solid solutions indicated that a thermodynamic equilibrium might account for the apparent La, Nd, and Eu solubilities. Conversely, the binary and ternary systems containing Tm₂O₃ as the heavy lanthanide oxide retained the oxide-based solid solutions, and their solubility behaviors were dominated by their congruent dissolutions. In the higher multicomponent system, the X-ray diffraction patterns of the solid phases, before and after contact with the aqueous phase indicated the formation of a stable oxide solid solution and their solubility behavior was explained by its congruent dissolution.

• Journal of Powder Materials
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• v.29 no.6
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• pp.499-504
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• 2022

The objective of this study is to assess the impact of spray drying conditions on medium-chain triglyceride (MCT) loading, solubility, and release of an MCT-loaded solid self-emulsifying system in a water-insoluble oily substance. MCT-loaded solid self-emulsifying systems are prepared by spray drying with SDS and calcium silicate. The effects of inlet temperature (60, 80, or 100℃) and feed solution composition (0, 10, 50, 90, or 100% ethanol) on physicochemical properties of MCT-loaded solid self-emulsifying systems are studied. The inlet temperature significantly affects the water solubility of MCT. Moreover, the feed solution composition significantly affects water solubility, release rate, and MCT loading. The MCT-loaded solid self-emulsifying system obtained at 60℃ using 90% ethanol feed solution shows the best physicochemical properties among the synthesized products and exhibits better water solubility (4.43 ± 0.44 vs. 0 ㎍/mL) and release (94.4 ± 1.6 vs. 32.8 ± 7.4%, 60 min) than a commercial product. Furthermore, the MCT-loaded solid self-emulsifying system shows an excellent emulsion droplet size (approximately 230 nm).

• 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.

• YAKHAK HOEJI
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• v.37 no.3
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• pp.216-227
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• 1993

Complex formations of practically insoluble antelmintic drugs such as mebendazole (MBZ), albendazole (ABZ) and flubendazole (FBZ) with dimethyl-$\beta$-cyclodextrin (DM-$\beta$-CyD) and 2-hydroxypropyl-$\beta$-cyclodextrin (HP-$\beta$-CyD) together with $\alpha$-, $\beta$- and $\gamma$-cyclodextrins(CyDs) in duffered solutions were investigated by solubility method. $A_{L}$ type phase solubility diagrams were obtained in all cases except for the complexation (B$_{s}$, type) of FBZ with $\gamma$-CyD. The highest stability constants were obtained with DM-$\beta$-CyD, followed by $\alpha$-CyD > $\beta$-CyD > HP-$\beta$-CyD > $\gamma$-CyD for ABZ, and HP-$\beta$-CyD > $\gamma$-CyD > $\beta$-CyD > $\alpha$-CyD for FBZ at pH 1.2. On the other hand, solid dispersion systems of ABZ and FBZ with $\beta$- and DM-$\beta$-CyDs were prepared by solvent evaporation method and evaluated by dissolution, differential thermal analysis and powder x-ray diffractometry. The dissolution rates of ABZ- and FBZ-DM-$\beta$-CyD solid dispersions were much faster than those of drugs alone, corresponding physical mixtures and tablets on market both at pH 1.2 and 6.8. Although dissolution rates of all samples at pH 6.8 were by far lower than those obtained at pH 1.2, as explained by pH-solubility profiles for ABZ and FBZ, the dissolution rates at pH 6.8 of ABZ from $\beta$- and DM-$\beta$-CyD solid dispersions exceeded the respective equilibrium solubility (23.9 $\mu\textrm{g}$/ml). Fast dissolution of ABZ from solid dispersions with CyDs was attributed to the reduction of drug crystallinity and particle size which was supported by DTA and powder x-ray diffractometry. Consequently these results suggest that solid dispersion systems with CyDs may provide useful means to markedly enhance the solubility and dissolution of benzimidazole antelmintic drugs.

• Journal of Pharmaceutical Investigation
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• v.25 no.1
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• pp.31-36
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• 1995

Solid dispersions and inclusion complex were prepared for the enhancement of solubility and dissolution rate of poorly water-soluble ibuprofen(IPF) as a model drug. Polyethylene glycol 4000(PEG4000) and polyvinylpyrrolidone(PVP) were used for the preparation of solid dispersion. $2-Hydroxypropyl-{\beta}-cyclodextrin(2-HP{\beta}CD)$ was also used for the preparation of inclusion complex. The solubility of IPF increased as the concentration of PEG4000, PVP and $2-HP{\beta}CD$ increased. Solubilization capacity of $2-HP{\beta}CD$ was increased about 10 times when compared to PEG 4000 and PVP. The dissolution rate of drug from solid dispersions and inclusion complex in the simulated gastric fluid was enhanced when compared to pure IPF and commercial $BR4^{\circledR}$ tablet as a result of improvement of solubility. In case of solid dispersions, dissolution rate of drug was proportional to polymer concentration in the formulation. The marked enhancement of dissolution rate of drug by inclusion complexation with $2-HP{\beta}CD$ was noted. However, dissolution rate of drug from solid dispersions and inclusion complex in the simulated intestinal fluid was not significant because IPF was readily soluble in that condition. From these findings, water-soluble polymers and cyclodextrin were useful to improve solubility and dissolution rate of poorly water-soluble drugs. However, easiness and reliability of preparation method, scale-up and cost of raw materials must be considered for the practical application of solid dispersion and inclusion complex in pharmaceutical industry.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.97-102
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• 2010

A novel surface-attached solid dispersion is designed to improve the solubility and oral bioavailability of poorly water-soluble drugs without crystalline change. Accordingly, it draws increasing interest because of excellent stability and no pollution for accomplishing enhanced solubility and bioavailability, which have recently been highlighted in connection with a number of higher value-added poorly water-soluble drugs. In addition, excellent stability can be attained when the poorly water-soluble drugs are not dissolved but dispersed in water and provide no crystallinity change. This solid dispersion is given by means of attaching the dissolved carriers such as hydrophilic polymer and surfactant to the surface of dispersed drug particles followed by changing the hydrophobic drug to hydrophilic form. The aim of the present review is to outline the preparation, physicochemical property and bioavailability of novel surface-attached solid dispersion with improved solubility and bioavailability of poorly water-soluble drugs without crystalline change.

• Korean Journal of Medicinal Crop Science
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• v.26 no.4
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• pp.317-327
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• 2018

Background: The root of Angelica gigas Nakai is used as a traditional herbal medicine in Korea for the treatment of many diseases. However, the poor water solubility of the active components in A. gigas Nakai is a major obstacle to its bioavailability. Methods and Results: This work aimed at enhancing the solubility of the active compounds of A. gigas Nakai by a chemical (using a surfactant) and physical (hot melt extrusion, HME) crosslinking method. Fourier transform infrared spectroscopy revealed multiple peaks in the case of the extrudate solids, attributable to new functional groups including carboxylic acid, alkynes, and benzene derivatives. Differential scanning calorimetry analysis showed that the extrudate soilid had a lower glass transition temperature ($T_g$) and enthalpy (${\Delta}H$) ($T_g:43^{\circ}C$, ${\Delta}H$ : < 6 J/g) as compared to the non-extrudate ($T_g:68.5^{\circ}C$, ${\Delta}H:123.2$) formulations. X-ray powder diffraction analysis revealed the amorphization of crystalline materials in the extrudate solid. In addition, enhanced solubility (53%), nanonization (403 nm), and a higher amount of extracted phenolic compounds were achieved in the extrudate solid than in the non-extrudate (solubility : 36%, nanonization : 1,499 nm) formulation. Among the different extrudates, acetic acid and span 80 mediated formulations showed superior extractions efficiency. Conclusions: HME successfully enhanced the production of amorphous nano dispersions of phenolic compound including decursin from extrudate solid formulations.

• KSBB Journal
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• v.31 no.4
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• pp.219-227
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• 2016

Valsartan, a drug for the treatment of cardiovascular disease, exhibited low bioavailability which was caused by, at least in part, limited solubility at low pH. Present investigation deals with the preparation and characterization of gastro-retentive drug delivery system (GRDDS) using valsartan solid dispersion. We prepared solid dispersion using surfactants (Poloxamer 407) and alkalizer ($Na_2CO_3$) which may to be useful for improving solubility of valsartan at low pH and evaluated by saturated solubility of valsartan in distilled water. Valsartan gastro-retentive (GR) tablets containing solid dispersion prepared and evaluated by weight variation, floating time and dissolution rate. Compression at lower pressures resulted in the tablets floating over simulated gastric fluid (pH 1.2) for more than 17 h. In vitro release of valsartan from GR tablet was dependent on the amount of poloxamer 407 and hydroxypropyl methylcellulose. On the basis of evaluation parameter, formulation E-3 was selected as a final formulation. Therefore, it can be concluded that the GR tablets containing solid dispersion may be exploited successfully for the delivery of poorly drug such as valsartan.