• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• KSBB Journal
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• 제26권4호
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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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• 제26권1호
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• pp.23-28
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• 1996

The dissolution characteristics of DDB were markedly enhanced by preparing solid dispersions of drug with polyethylene glycol 6000. Solid dispersions of various weight fraction were formed by a melting method. And various tablets$(A{\sim}E)$ were prepared from these solid dispersions with excipients (lactose, com starch, Avicel and PVP) by wet granulation method. There were no significant differences in dissolution rates between physical mixture and DDB alone. But dissolution rates of solid dispersions were $1.4{\sim}2.0$ times greater than that of DDB alone and $1.2{\sim}1.8$ times greater than those of a commercial tablet.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.118-118
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• 1997

Solid dispersions were used to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) in water, with the ultimate goal of optimizing its bioavailability when incoporated into pharmaceuticals. Carriers used were Kollidon 30, Kollidon VA 64, 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD), sodium salicylate or sodium benzoate. DDB solid dispersions were prepared at drug to carrier proportions ranging from 1 : 5 to 1 : 20 (w/w) by solvent evaporation method. DDB tablets (7.5 mg) were prepared by compressing the powder mixture composed of solid dispersions, lactose, corn starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were prepared by filing the mixture into empty hard gelatin capsules (size #1). Dissolution studies of DDB from powdered solid dispersions, tablets and capsules were performed in 900 $m\ell$ of water at 100 rpm and 37$^{\circ}C$ by the paddle method. The dissolved amount was assayed by HPLC and expressed as the mean(%)of three determinations.

• Journal of Pharmaceutical Investigation
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• 제18권4호
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• pp.181-186
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• 1988

Inclusion complex of sulfamethoxazole with ${\beta}-cyclodextrin$ was prepared by freeze-drying method in molar ratios of 1:1, 1:1.25, 1:1.5 and 1:1.75, and the complex formation was identified by ultraviolet and infrared spectroscopies, powder X-ray diffractometry and differential scanning calorimetry. Dissolution rate and solid state stability of the complex were investigated in comparison with those of sulfamethoxazole powder and the physical mixture of sulfamethoxazole with ${\beta}-cyclodextrin$. As a result, the dissolution rate and the stability of solid complexes in various relative humidity conditions increased more remarkably than those of sulfamethoxazole powder and physical mixture. But the difference according to molar ratio of the complex was not recognized.

• 약학회지
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• 제56권3호
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• pp.164-172
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• 2012

This study was aimed to increase the solubility, dissolution and permeation rates of atorvastatin calcium (ATC) using bile salt and/or 2-hydroxypropyl-${\beta}$-cyclodextrin ($HP{\beta}CD$). From solubility studies, sodium deoxycholate (SDC) among bile salts studied was found to have the highest solubilizing effect on ATC ($4.4{\pm}0.4$ mg/ml), and the order of increasing solubility was SDC>sod. cholate>sod. glycocholate>sod. taurodeoxycholate>sod. taurocholate>conjugated bile acid. ATC solid dispersions were prepared at various ratios of drug to SDC and/or $HP{\beta}CD$, and evaluated by differential scanning calorimetry (DSC), dissolution studies and dissolution-permeation studies. DSC curves showed amorphous state of ATC in the physical mixture and solid dispersion. Dissolution rates of ATC-SDC solid dispersions and physical mixture were markedly increased at pH 6.8, but decreased at pH 1.2 with greater proportions of SDC due to the precipitation of SDC, compared with that of drug alone. On the other hand, dissolution rates of ATC-$HP{\beta}CD$ solid dispersion and physical mixture at pH 1.2 were varied with the ratio of drug to carriers. From duodenal permeation studies, it was found that fluxes of ATC (donor dose: 0.5 mg/3.5 ml) in the presence of 25 mM sodium glycocholate, SDC, sod. cholate and sod. taurocholate $(5.7{\pm}0.9$, $5.6{\pm}0.9$, $4.8{\pm}0.7$ and $4.6{\pm}0.9\;{\mu}g/cm^2/hr$, respectively) were enhanced, compared with drug alone ($3.4{\pm}0.9\;{\mu}g/cm^2/hr$). In the dissolution-permeation studies, 1 : 9 : 10 (w/w) ATC-SDC-$HP{\beta}CD$ solid dispersion increased the flux 2.2 times, compared with 1 : 5 : 4 (w/w) ATC-lactose-corn starch mixture as control. In conclusion, solid dispersions with bile salt and $HP{\beta}CD$ were found to be an effective means for increasing the dissolution and permeation rates of ATC.

• Journal of Pharmaceutical Investigation
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• 제25권1호
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• pp.37-46
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• 1995

The experiment was designed to investigate the sustained release dosage form of silymarin (SL) from chitosan (CS) carrier. Solid dispersed system was prepared by mixing the drug with chitosan. This solid dispersed system was cross-linked by glutaraldehyde, formaldehyde, acetaldehyde and butylaldehyde, respectively. The dissolution rates of these preparations were compared with each other in vitro. The silymarin was mired with anionic alginate gel and bead was prepared by dropping this mixture to cationic chitosan solution including calcium chloride. Chitosan encapsulated alginate bead after drying in the oven was investigated for the dissolution rate. The dissolution rate of SL-CS mixture was delayed with increase in the amounts of CS and the concentration of aldehyde. The effect on the delay of dissolution rate was in the increasing order of formaldehyde, glutaraldehyde, acetaldehyde, butylaldehyde. The dissolution rate of chitosan encapsulated alginate bead was parallel with the concentration of chitosan in diluted hydrochloric acid solution and delayed with increase in the concentration of chitosan in phosphate buffer solution.

• Journal of Pharmaceutical Investigation
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• 제21권1호
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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.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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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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• 제34권2호
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• pp.91-94
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• 2004

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution ad dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based sold suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Ver small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about $32^{\circ}C$ was a sold for at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue colo of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/ P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in thε rectum for at least 4 h. Our results indicated that the poloxamer-based sold suppository with P 124 and P 188 would be a candidate of rectal dosage form for diclofenac sodium.