• Journal of Pharmaceutical Investigation
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• v.37 no.1
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• pp.1-5
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• 2007

Solid dispersions of piroxicam were prepared by melting method using poloxamer as a carrier. The results of DSC and XRD studies showed that the amorphous farm of piroxicam coexisted with the crystalline form in the solid dispersions. However, the ratio of crystalline form of piroxicam in the solid dispersion prepared by melting method decreased in comparison with the same ratio of the solid dispersion prepared by solvent method. As the ratio of poloxamer in the solid dispersion increased, the ratio of the amorphous form of piroxicam in the solid dispersion increased. The dissolution rate of piroxicam from the solid dispersions was significantly higher than that from piroxicam powder. In comparison to the solid dispersion prepared by solvent method, the dissolution rate of piroxicam from the solid dispersion prepared by melting method was higher. As the ratio of poloxamer in the solid dispersion prepared by melting method increased, the initial dissolution rate decreased, however, the total amount dissolved at the end of the study increased.

• KSBB Journal
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• v.26 no.4
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• pp.283-292
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• 2011

Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.

• 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.

• 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.

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.295-301
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• 1997

Nitrendipine, a slightly soluble calcium channel blocking agent forms a solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$, which exhibits better dissolution characteristics than the uncomplexed drug. The dissolution rate of nitrendipine was markedly increased in solid dispersion system in pharmacopeial disintegration media at pH 1.2 and pH 6.8. Four different dosage forms of nitrendipine were administered to rats: (a) nitrendipine in the solution of PEG 400; (b) nitrendipine solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 by solvent evaporation method and administered in capsule form; (c) physical mixture of nitrendipine with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 and administered in capsule form; (d) nitrendipine alone administered in capsule form. Relative bioavailability after the oral administration of various dosage forms to rats with a dose of 10 mg/kg equivalent to nitrendipine was compared with that of nitrendipine in the solution of PEG 400. The AUC of solid dispersion was significantly bigger than that of nitrendipine powder. $T_{max}$ of solid dispersion was significantly shorter and $C_{max}$ was higher than that of nitrendipine powder. These results indicate that the bioavailability of nitrendipine could be improved markedly by inclusion complexation. An interesting correlation also appears to exist between the in vitro dissolution data and the area under the plasma concentration-time curves.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Journal of Pharmaceutical Investigation
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• v.22 no.1
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• pp.33-40
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• 1992

This study was aimed to control the release characteristics of ketoprofen by microencapsulating $ketoprofen-{\beta}-cyclodextrin\;(KF-{\beta}-CyD)$ solid dispersion with Eudragit RS by the phase separation method using a nonaqueous vehicle. KF alone was also microencapsulated with Eudragit RS by the evaporation process in water phase. The results obtained showed that it was not possible to microencapsulate KF alone by phase separation in a chloroform-cyclohexane system while it was easy to microencapsulate $(KF-{\beta}-CyD)$ solid dispersion system. For the microcapsules, the release test was performed in the first fluid (pH 1.2) and the second fluid (pH 6.8) of K.P.V disintegration medium at $37^{\circ}C$. The release of KF from $(KF-{\beta}-CyD)$ solid dispersion microcapsules (1:1 core wall ratio) was more sustained than that from KF microcapsules, and followed zero-order kinetics. Especially, solid dispersion microcapsules showed pH-independent release patterns with higher wall to core ratio (1:1 w/w).

• YAKHAK HOEJI
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• v.54 no.4
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• pp.316-321
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• 2010

Adefovir dipivoxil which was originally developed by Gilead Sciences has been used as treatments of HIV and HBV, especially a therapeutics for HBeAg positive and negative chronic patients. We developed highly efficient purification method using reverse phase column chromatography for mass production and a stable amorphous Adefovir dipivoxil using solid dispersion method. Reverse phase column chromatography led to highly pure product, more than 99.7% by HPLC and can be used for mass production compared with normal column chromatography. Solid dispersion method containing watersoluble polymer and Isomalt showed improved stability of amorphous Adefovir dipivoxil against heat and moisture.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.173-179
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• 2002

Solid dispersions of ipriflavone with PVP were prepared by a spray-drying method in order to improve the bioavailability. They were measured with scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction, and Fourier transform infrared spectroscopy to evaluate the physicochemical interaction between ipriflavone and PVP and study the correlation between these physicochemical characteristics and bioavailability. Ipriflavone exhibited crystallinity, whereas PVP was almost amorphous. The area of the endotherm $({\Delta}H)$ of freezer milled ipriflavone, freezer milled ipriflavone physically mixed with freezer milled PVP, and physically mixed ipriflavone with PVP was almost the same, whereas ${\Delta}H$ of the solid dispersed ipriflavone with PVP was much smaller than that of the other preparation types. Also, the crystallinity and the crystal size of ipriflavone in the solid dispersed ipriflavone with PVP were much smaller than those of the other preparation types. From the in vivo test, the AUC of the solid dispersed ipriflavone with PVP was approximately 10 times higher than that of the physically mixed ipriflavone with PVP. The solid dispersion using the spray-drying method with a water-soluble polymer, PVP, may be effective for the improvement of the bioavailability.

• Journal of Pharmaceutical Investigation
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• v.21 no.1
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• pp.11-22
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• 1991

The purpose of this study was for the enhancement of dissolution rate of ketoprofen. The solid dispersions composed of ketoprofen(KP) and polyethylene glycol(PEG) 4000 or 6000 were prepared by fusion method at various ratios of KP to PEG (0.5 : 10, 1 : 10, 2 : 10, 3 : 10 and 4 : 10(w/w)) and their physical mixtures were also prepared at the above ratios. Dissolution tests, X-ray diffraction study and differential scanning calorimetry study were carried out. It was found that the dissolution rates of solid dispersion and physical mixture at any ratio of the two components discribed above were greater than that of the pure ketoprofen. X-ray diffraction studies of ketoprofen suggested that less than 1 to 10 ratio of ketoprofen to PEG4000 (or 6000) was required to dispersion amorphous state in the carrier. In addition, the studies of DSC showed that ketoprofen had a sharp endothermic peak at $94^{\circ}C$ but not for the solid dispersion at the same temperature.