• 약학회지
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• 제37권3호
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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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• 제32권1호
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• pp.27-33
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• 2002

A self-microemulsifying drug delivery system(SMEDDS) composed of Cremophor $EL^{\circledR},\;Labrasol^{circledR}$, and Lauroglycol $FCC^{circledR}$ was prepared for the enhancement of solubility, dissolution rate and bioavailability of ibuprofen(IBP), which is water-insoluble but soluble in oils and surfactants. Phase diagram with various regions including microemulsion area was depicted. The SMEDDS was encapsulated in soft gelatin capsules and their dissolution characteristics in various media were observed in comparison to the generic products commercially available in the market. Soft capsules of SMEDDS formulation showed better dissolution profiles, especially in acidic condition, than the others. For the period of 1 hr dissolution in pH 1.2 medium, it reached over 70% dissolution from soft capsules, compared to less than 40% dissolution from commercial reference tablets. On the other hand, in vivo pharmacokinetic parameters were obtained after oral administrations of different IBP preparations to Sprague Dawley rats. SMEDDS formulation showed higher $C_{max}$ and greater $AUC_{0-5hr}$ than the suspension of reference tablet or IBP powder. Therefore, it is possible to conclude that a newly developed soft capsules employing SMEDDS provides an alternative preparation to improve oral bioavailability of IBP.

• 한국광물학회지
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• 제13권3호
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• pp.121-137
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• 2000

공주군 유구 일대의 화강암질편마암은 온대습윤기후의 지형적 영향에 기인한 산성환경 및 양호한 배수조건에서의 풍화작용으로 두께가 8m인 깊은 saprolite층과 50cm 이상의 두꺼운 토양층을 형성하였다. 풍화단면에서는 흑운모/질석혼합층 광물, 삼팔면체, 할로이사이트, 캐올리나이트, 일라이트, 이팔면체질식, 스백타이트, 깁사이트, 침철석 등의 풍화광물이 확인되었다. 흑운모의 변질은 질석화작용이 미약한 반면에 풍화단면 전반에서 고령토화작용이 매우 현저한 풍화양상을 보여주며, 흑운모-흑운모/질석 혼합층 광물-질석, 흑운모-할로이사이트, 캐올리나이트, 깁사이트 및 흑운모-일 라이트의 풍화과정을 나타낸다. 흑운모의 풍화작용으로 생성된 고령토광물은 주로 할로이사이트이며, 고령토화작용으로 방출된 Fe는 변질된 흑운모 주변에서 침철석을 형성한다 사장석은 용해-침전작용으로 관상의 할로이사이트를 형성한다. 할로이사이트의 산출양상은 사장석의 용해유형에 따라 방향성이 강한 할로이사이트 집합체와 매우 구불구불한 할로이사이트 집합체로 나타난다. 모암에서 철을 함유하고 있던 광물은 용해되어 모암광물의 가상을 유지한 채 또는 그 주변에서 침철석을 형성한다. 연구지역 화강암질편마암의 단면은 풍화도가 증가할수록 모암 구성광물이 감소하는 반면에 점토광물의 양이 증가하는 전형적인 풍화 양상을 보여주며, 광물의 풍화작용은 산성환경과 양호한 배수환경과 같은 지역적인 조건에 영향을 받아 복잡하고 다양한 풍화광물을 형성하였다.

• Journal of Pharmaceutical Investigation
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• 제23권3호spc1호
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• pp.9-18
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• 1993

Sugar spheres loaded with melatonin (MT) were coated with $Aquacoat^{\circledR}$ to control the release rate of MT over 8 hours. A zero-order release pattern over 8 hours was obtained with 20% coating on 8-10 mesh beads in USP basket dissolution studies. MT in 20% coated beads was quite stable at room temperature with less than 5% MT degraded during 6 months' storage. Dissolution profiles were also unchanged after 6 months. An oral preparation containing MT-loaded uncoated beads for immediate release and 20% coated beads with $Aquacoat^{\circledR}$ for controlled release over 8 hours was evaluated in six human subjects. When total 0.5 mg MT as low dose (immediate release portion of MT, 0.1 mg) was administered to four subjects, average peak plasma MT concentration was reached at about 600 pg/ml and maintained at about 10 pg/ml over 8 hours. Plasma MT concentration-time profiles were similar in shape to computer-simulated profiles. However, maximal plasma MT concentrations were three times greater compared to computer simulated curve. These results suggest that MT dose, ratio of immediate and controlled release MT, and pharmacokinetic parameters selected are adjusted to mimic endogenous MT concentration-time curve. In another study, 0.2 mg MT having 10% of immediate release portion and 80% controlled release portion produced plasma MT concentration-time curve which is more similar to endogenous profiles. A low bioavailability (<20%) may result from extensive first pass metabolism and remaining amounts of MT from controlled beads. A good correlation between plasma MT concentration and urinary excretion rate of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT was observed. As plasma MT concentration increased, urinary excretion rate of 6-STMT increased concomitantly. The linear relation between plasma MT and urinary excretion rate of 6-STMT was statistically significant. This result suggests that urinary 6-STMT may be used as an index of circadian rhythms of MT in humans.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.219-223
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• 1995

Rectal absorption of opeprazole, a proton pump inhibitor, from suppositories was studied in rabbits. The suppositories were prepared by the conventional melting method with two types of bases, water-soluble polyethylene glycol (PEG) 4000 and oil-soluble Witepsol H15 bases, and administered intractally (ir) to rabbits at a dose of 10 mg omeprazole/kg. The plasma omeprazole concentration-time profiles of the two suppositories were compared with those following intravenous 9iv) administration of the same dose. There were no significant differences between the two suppositories in bioabailabilities and peak plasma concentrations $(C_{max})$. Bioavaiabilities and $C_{max}$ of PEG- and Witpsol suppositories were 30.3 and 33.9%, and 7.0 and $5.6\mug/ml$, resepectively. However, PEG suppository showed significantly (p<0.05) shorter time to reach peak plasma concentration $(T_{max})$ mean absorption time (MAT) and mean residence time in the plasma (MRT) than Witepsol suppository. The $T_{max}$ MRT nad MAT were 25.0, 83.0 and 38.5 min for PEG syppository, but were 90.0, 122.5 and 78.0 min for Wiepsol supposiotory, respectively. These differences between thw two suppositories could be explanined by the difference in the in vitro dissolution rates between the suppositories. The dissolution of omeprazole form PEG suppository was reportedly much faster than that from Witepsol suppository. It suggests that plasma profiles of omeprazole, especially $C_{max}$ MAT and MRT, could be controlled by modifying the in vitro dissolution rate of the drug from the suppositories. Above results suggest that rectal suppository is worth developing as an alternative dosage form of omeprazole to the conventional oral preparations which need sophisticated treatments, such as enterix coating, to prevent acid degradation of the drug in the stomach fluid.

• Journal of Pharmaceutical Investigation
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• 제41권1호
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• pp.51-57
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• 2011

The objective of this study was to enhance the utilitization of Ibuprofen (IBU) by introducing the fast-disintegrating tablet (FDT) form. Presently, IBU is being widely used as a tablet or syrup form. But in contrast to these two formulations, IBU as FDT is not only convenient but also increases the control over the time release of the drug, noted by using Alginate beads. This study was carried out with Sodium Alginate and IBU at the ratios of 1:0, 1:0.5, 1:1, and 1:2 in order to produce a series of beads with different ratios. During the drying process of the beads, talc was added in beads to compare the effects with and without the talc. The final product was scanned with SEM imaging to determine the difference in the surface of the beads. The parameters assessed were the diameter, content assay, dissolution test and effectiveness of time-release. Direct compression method was used to prepare FDT containing IBU bead. The properties of FDT, such as hardness, disintegration time, were investigated. The dissolution profiles of FDT were tested using KP dissolution apparatus 1 (basket method). The results suggest addition of talc and drying the beads made the surface smooth and less vulnerable to clutter into chunks. The size of beads was less than 300 ${\mu}m$ which did not create a sandy feeling in the mouth. Thus, the beads formulation model made the sustained release of the drug possible, the hardness of FDT (1.25~1.50 $Kg/cm^2$) was acceptable and all the values of dissolving period were less than 30 seconds. The dissolution profile of FDT was same as that of IBU bead. The efficient dissolution profile and low price of IBU bead containing Sodium Alginate, the FDT formulation prepared from IBU bead can save the expenses and can improve the convenience of application of this drug.

• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.279-285
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• 2005

Ground CS-891 (N-[1-(4-methoxyphenyl)-1-methylethyl]-3-oxo-4-aza-5a-androst-1-ene-$17{\beta}$-carboxamide) of poorly water soluble drug was obtained using a Heiko Seisakusho model TI-100 vibration mill, and samples with different crystallinity were prepared at mixture ratios of 10:0, 7:3, 5:5, 3:7 and 0:10 (intact;ground CS-891). Physicochemical characterizations were obtained using qualitative and quantitative X-ray diffractometry, different scanning calorimetry (DSC), scanning electron microscopy (SEM), Quantasorb surface area analyzer, and controlled atmosphere microbalance. With increase of amorphous CS-891 in mixture ratios, the intensities of X-ray diffraction peaks of crystalline CS-891 were decreased, whereas surface area, water absorption, and exothermic peaks in DSC were increased. The apparent solubility of ground CS-891 was $4.4\;{\mu}g/ml$ and the solubility of intact CS-891 was $3.1\;{\mu}g/ml$ at $37{\pm}1^{\circ}C$. The apparent precipitation rates of CS-891 in a supersaturated solution during the solubility test were increased with an increase of amorphous CS-891, and a crystalline form of CS-891 transformed from amorphous CS-891 after the solubility test was found by X-ray diffraction analysis, DSC and SEM. The dissolution profiles of CS-891 with different crystallinity at $37{\pm}1^{\circ}C$ by the USP paddle method were investigated, and the apparent dissolution rate constant of ground CS-891 was about 5.9-fold higher than that of intact CS-891. A linear relationships between the crystallinity of CS-891 and the apparent dissolution rate constant (r>0.96) were obtained.

• Journal of Pharmaceutical Investigation
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• 제21권1호
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• pp.23-32
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• 1991

Dissolution profiles of ketoconazole in solid dispersion system (SDS) were investigated in the second fluid (pH 6.8) for the dissolution test (KPV). PVP K-30 and methyl cellulose were used as carriers in SDS, and chloroform as a solvent. Computer optimization technique was applied to obtain an optimum formula of SDS, and the following results were obtained; 1) Dissolution rate of ketoconazole in SDS was larger than that of pure ketoconazole in the second fluid of pH 6.8. 2) PVP K-30 and methyl cellulosr were good carriers for SDS of ketoconazole. Moerover PVP K-30 was better than methyl cellulose. 3) The optimum formula of ketoconazole SDS obtained from computer optimization technique was chloroform 175 ml, PVP K-30 5g and methyl cellulose 0.2g per 1g of ketoconazole. 4) The experimental value of $A_{60}$ (Amount released from ketoconazole tablet during 60 minutes) obtained from SDS by optimum formula agreed well with the value calculated by polynomial regression equation.

• Journal of Pharmaceutical Investigation
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• 제32권4호
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• pp.305-311
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• 2002

In order to evaluate the effect of poloxamer 407 content on the dissolution profiles of pellets, diltiazem HCl (DTL) core pellets were prepared with poloxamer 407 (50-90% w/w, with lactose as filler) using an extruder and a spheronizer. Any possible interaction between the drug and excipients was evaluated using DSC, IR and TLC. Dissolution tests were performed using USP basket method. In addition, scanning electron micrograph was performed to examine the surface roughness and cross sections. The release of DTL from the core pellets was decreased with increasing poloxamer 407 content. Cracks appeared on the surface of the core pellets with increasing the poloxamer 407 content, which may play a role on the retardation of the release of DTL from core pellets. There was no any significant interaction between the drug and excipients employed to prepare the core pellets.

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.451-456
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• 2009

The purpose of the present study was to evaluate the bioequivalence of two ciprofloxacin tablets, Ciprobay (Bayer Korea Ltd.) and Rofcin (Binex Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The release of ciprofloxacin from the two ciprofloxacin tablets in vitro was tested using KP XIII Apparatus I method with dissolution media (0.01 M HCl). The dissolution profiles of two ciprofloxacin tablets were very similar at dissolution media. Twenty four healthy male volunteers were divided into two groups and a randomized 2$2{\times}2$2 cross-over study was employed. After one tablet (250 mg ciprofloxacin) was orally administrated, blood was taken and the concentrations of ciprofloxacin in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two ciprofloxacin tablets based on the Ciprobay were -0.63%, 3.98% and -9.23%, respectively. There were no sequence effects between two tablets in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25)(e.g., log(0.9520)~log(1.0523) and log(0.9689)~log(1.1663) for $AUC_1\;and\;C_{max}$, respectively). Thus, Rofcin tablet was bioequivalent to Ciprobay tablet.