• 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.

• Bulletin of the Korean Chemical Society
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• v.29 no.4
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• pp.749-754
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• 2008

To increase the solubility of sibutramine freebase, the solid dispersion was prepared using a fluid-bed granulator. The solid dispersion containing sibutramine freebase was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). After filling the sibutramine solid dispersion in the gelatin hard capsule, we performed in vitro dissolution test, the stability test under accelerated conditions and pharmacokinetic study in beagle dogs. The DSC and XRD data showed that sibutramine solid dispersion would be amorphous state. The dissolution rate of sibutramine solid dispersion was significantly increased about 70% than sibutramine freebase. The stability of sibutramine solid dispersion capsules was equivalent or above to commercial product of sibutramine. In beagle dogs, the sibutramine solid dispersion showed equivalent pharmacokinetic behavior with commercial product of sibutramine hydrochloride. In conclusion, the solid dispersion system provided a possible way to overcome the low solubility of sibutramine freebase, and the sibutramine solid dispersion can be a bioequivalent with the commercial product in humans.

• 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.

• 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).

• 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.

• 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.

• 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.125-142
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• 2011

Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailability. Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by various methods has many advantages. However, despite numerous studies which have been carried out, limitations for commercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous form of solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuously decrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on the effects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from the first generation to the recent third generation products. In this review, an overview on solid dispersions in general will be given with emphasis on the various manufacturing processes which include the use of polymers and on the stabilization strategies which include methods to prevent crystallization.

• Journal of Pharmaceutical Investigation
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• v.19 no.2
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• pp.109-116
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• 1989

Solid dispersion of fenticonazole nitrate (FN) with poloxamer 407, polyethylene glycol 6000, povidone (K-90) were prepared by the solvent method. To characterize the state of the drug in solid dispersions, the x-ray diffractometry and differential scanning calorimetry were carried out. The identification of these systems suggested that FN in the poloxamer 407 system remained in crystalline state, and the drug in the PVP system was amorphous. A marked increase in the dissolution rate of FN was attained by dispersing the drug in the hydrophilic polymers used, and the dispersion with poloxamer 407 was superior to the other two carriers in releasing the drug into solution.

• 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.