• Journal of Pharmaceutical Investigation
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• 제13권3호
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• pp.104-109
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• 1983

The effect of diluents on the dissolution rate of indomethacin was studied and the dissolution rate for the marketed products was compared to establish the quality standard for indomethacin preparation. The results are as fellows 1. The effect of test methods was not significant in the case of paddle method but was greatly effected in the case of basket method. 2. The effect of diluents was not significant generally, but in the case of starch dissolution rate was greatly effected. 3. The dissolution rate was remarkably decreased in proprotion to increase of capsule size. 4. The marketed products met the KP dissolution requirement but showed a little difference due to manufacturers.

• Journal of Pharmaceutical Investigation
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• 제28권2호
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• pp.81-85
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• 1998

Three polymorphic modifications and two pseudopolymorphic modifications of cefotaxime sodium were obtained by crystallization from different organic solvents. The isolated crystal forms were characterized by UV spectrophotometry, DSC, TGA and X-ray crystallography. Crystal forms of cefotaxime sodium were also compared by dissolution rate. The dissolution rate of form 1 was the highest, followed by form 2, form 4, form 6, form 5 and form 3. Among these polymorphic modifications the dissolution rate of form 3 and form 5 was much slower than that of cefotaxime sodium on the market. All forms showed no change after 2-month storage test in the silica gel desiccator. But after the storage of 2-month at 95% relative humidity condition, all forms were deliquesced by hygroscopic property except form 1 that showed the highest dissolution rate. At 52% relative humidity condition, form 1, form 2 and form 6 had no evidence of phase transformation, but form 3, form 4 and form 5 were also deliquesced.

• Journal of Pharmaceutical Investigation
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• 제20권4호
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• pp.193-198
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• 1990

To increase the dissolution rate of furosemide, cogrinding or coprecipitating of furosemide with povidone was carried out. The ground mixture of furosemide with povidone was prepared by cogrinding in a ceramic ball mill and the coprecipitate was prepared by solvent method using methanol. The povidone ground mixture and the coprecipitate showed a faster and more enhanced dissolution rate than the physical mixture or intact furosemide. The IR, DTA and TGA studies showed the physicochemical modifications of furosemide from the ground mixture and the coprecipitate. An interaction, in the ground mixture and in the coprecipitate, such as association between the functional groups of furosemide and povidone might occur in the molecular level. The coprecipitating and cogrinding techniques with povidone provided a promising way to increase the dissolution rate of poorly soluble drugs.

• Journal of Pharmaceutical Investigation
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• 제14권1호
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• pp.1-10
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• 1984

Effects of water soluble carrier on the dissolution characteristics of indomethacin coprecipitates were investigated. Water soluble carriers used were polyvinylpyrrolidone, dextrose, mannitol and their mixtures of various ratios. The dissolution rates of indomethacin from coprecipitate with ratios of drug-to-carrier, kinds of carrier and ratios of carriers were as follows: 1. The dissolution rates increased proportionally to the ratios of carrier in the case of both single and combined carrier, and the dissolution rate of coprecipitate with the combined carrier was more rapid than that with single carrier. 2. The combined carrier of PVP-dextrose (1 : 2) in the case of the coprecipitate of drug-to carrier (1 : 1) and PVP-dextrose (4 : 1) in the case of the coprecipitate of drug-to carrier (1 : 3) yield the most rapid dissolution rate. 3. The dissolution rate of indomethacin was the most markedly enhanced in the case of the combined carrier of PVP and dextrose.

• Journal of Pharmaceutical Investigation
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• 제22권2호
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• pp.105-113
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• 1992

To improve the solubility and dissolution rate of trimethoprim (TMP), which is slightly soluble drug, its inclusion complexes were prepared and studied in this experiment. Inclusion complexes of TMP with ${\beta}-cyclodextrin$ and ${\beta}-cyclodextrin$ polymer (CDPS) were prepared according to Fenyvesi method. These were compared with TMP and its physical mixture with CDPS. Water, diluted hydrochloric acid and phosphate buffer solution were used as dissolution media. And accelerated stability test was studied at $50,\;70\;and \;80^{\circ}C$. It was found that solubility and dissolution rate of inclusion complexes were increased in water. Especially, the solubility and dissolution rate of TMP was found to be markedly increased by inclusion complexation with CDPS. In stability test, ${\beta}-cyclodextrin$ inclusion complexes were more or less stable than TMP alone. This tendency was not led in CDPS. Consequently, CDPS was useful in increasing dissolution rate and stability of TMP.

• Journal of Pharmaceutical Investigation
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• 제25권1호
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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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• 제29권3호
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• pp.227-234
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• 1999

Solid dispersions were prepared to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) using water-soluble carriers such as povidone, copolyvidone, $2-hydroxypropyl-{\beta}-cyclodextrin (HPCD)$, sodium salicylate or sodium benzoate by solvent evaporation method. Solid dispersions were characterized by infrared spectrometry, differential scanning calorimetry (DSC) and powder X-ray diffractometry, dissolution and permeation studies. DDB tablets (7.5 mg) were prepared by compressing the powder mixtures composed of solid dispersions, lactose, com starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were also prepared by filling the mixtures in empty hard gelatin capsules (size No.1). From the DSC and powder x-ray diffractometric studies, it was found that DDB was amorphous in the HPCD or copolyvidone solid dispersions. Dissolution rates after 10 min of DDB alone and solid dispersions (1 : 10) in sodium benzoate, sodium salicylate and copolyvidone were 11.8, 23.5, 22.8 and 82.5%, respectively. Dissolution rates of DDB after 30 min from 1 : 10 and 1 : 20 copolyvidone solid dispersions were 80.5 and 95.0%, respectively. For the DDB tablets prepared using solid dispersions (1 : 20), the initial dissolution rate was dependent on carrier material, and was ranked in order, $Kollidon\;30\;{\ll}$ copolyvidone < HPCD. For the HPCD solid dispersion tablets, dissolution rate reached 97.4% after 15 min, but thereafter slowly decreased to 80.7% after 2 hr due to the precipitation of DDB. However, in the case of copolyvidone solid dispersion tablets, dissolution increased linearly and reached 93.4% after 2 hr. Reducing the volume of test medium from 900 to 300 ml markedly decreased the dissolution rate of the tablets containing 1 : 20 HPCD solid dispersions and 1 : 10 copolyvidone solid dispersion. For 1 : 20 copolyvidone solid dispersion tablets, there was no significant change in dissolution rate up to 1 hr with different volumes of test medium. Preparation of the copolyvidone solid dispersion (1 : 20) in capsules markedly delayed the dissolution (31.2 % after 2hr) due to the limited diffusion within capsules. The permeation rate $(13.4\;g/cm^2\;after\;8\;hr)$ of DDB through rabbit duodenal mucosa from copolyvidone solid dispersion (1 : 10) was markedly enhanced, when compared with drug alone or physical mixtures. From overall findings, DDB formulations containing copolyvidone solid dispersions (1 : 20) could be used to remarkably improve the dissolution rate in dosage form of powders and tablets.

• Journal of Pharmaceutical Investigation
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• 제17권3호
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• pp.135-139
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• 1987

This study was attempted to investigate the dissolution rate and the bioavailability of commercially available sulfamethoxazole and trimethoprim (SMX-TM) tablets in rabbits. The dissolution test was conducted in artificial gastric juice by basket method with eight SMX-TM tablets which were chemically equivalent. According to the dissolution rate, SMX-TM tablets were divided into four groups, such as rapid, intermediate, slow and very slow groups for the bioavailability test in rabbits. The results were as follows: 1) The dissolution rate of brand A was most rapid but brand H was most slow in artificial gastric juice. 2) Area under the blood concentration curve was larger in the order of brand A > C > E > H in rabbits. 3) There was a little difference in pharmacokinetic parameters such as biological half life, absorption rate constant and $t_{max}$. 4) The relationship between the dissolution rate and relative bioavailability was significant in brand A, C, E and H. From the results of this experiment, the bioavailability of SMX-TM tablets in rabbits may be predicted from the results of dissolution rate studies.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.257-266
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• 1998

To improve the solubility and dissolution rate of acyclovir (ACV), which is low oral bioavailability due to its properties of slight solubility in water and incomplete gastrointestinal absorption, the solid inclusion complexes of ACV with ${\alpha}CD$, ${\beta}CD$, $DM{\beta}CD$ in molar ratio of 1:1 were prepared by the freeze-drying method. The inclusion complexes were investigated by solubility study, UV, IR and DSC. The dissolution rate of ACV was significantly increased by ACV-CDs inclusion complex formation in artificial intestinal fluid at pH 6.8. The enhanced dissolution rate of ACV could be due to an increase of solubility and the formation of an amorphous structures through inclusion complexation with CDs. Especially, $ACV-DM{\beta}CD$ inclusion complex enhanced the maximum plasma concentration levels and AUC following oral administration compared to those of ACV alone. The present results suggest that $ACV-DM{\beta}CD$ inclusion complex serves as a potential carrier for improving the solubility, the dissolution rate and the bioavailability of ACV.

• Archives of Pharmacal Research
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• 제28권1호
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• pp.120-126
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• 2005

The objective of this study was to investigate the effects of sodium lauryl sulfate upon the saturation solubility of carbamazepine, its dissolution kinetics, and $T_{50\%}$ defined as the time required for dissolving $50\%$ of carbamazepine. Water, 0.1N-HCI, and phosphate buffers at pH 4.0 and 6.8 containing 0.1, 0.5, 1, and $2\%$ sodium lauryl sulfate were used as dissolution media. The dissolution study was conducted by using the USP dissolution apparatus II with an agitation rate of 75 rpm. Samples of the dissolution media were taken in 7, 15, 30, 45, 60, 75, and 90 min, and the amounts of carbamazepine were determined spectrophotometrically at 285 nm. All dissolution data were fitted well into a four-parameter exponential equation: $Q\;=\;a(1\;-\;e^{-bxt})\;+\;c(1\;-\;e^{-dxt})$. In this equation Q represented $\%$ carbamazepine dissolved at a time t, and a, b, c, and d were constants. This equation led to the calculation of dissolution rates at various time points and $T_{50\%}$. It was found that the dissolution rate of carbamazepine was directly proportional to the aqueous concentration of sodium lauryl sulfate. In addition, under our experimental conditions $T_{50%}$ values ranged from 37.8 to 4.9 min. It was interesting to note that $T_{50\%}$ declined rapidly as the surfactant concentration increased from 0.1 to $0.5\%$, whereas it declined more slowly at concentrations greater than $1\%$. These results clearly demonstrated that the dissolution rate of carbamazepine and duration of its dissolution test could be tailored by optimizing the amount of sodium lauryl sulfate in a dissolution medium.