• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.299-304
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• 2006

The aim of this study was to investigate the effect of deformable liposomes with sodium cholate on the skin permeation and skin deposition of arbutin, a hydrophilic skin-whitening agent. Various compositions of liposomes were prepared by the extrusion method. Particle size distribution and entrapment efficiency were determined by the laser light scattering and the gel permeation chromatography, respectively. The in vitro rat skin permeation and deposition of arbutin in various skin layers were investigated using the Keshary-Chien diffusion cells at $37^{\circ}C$. The average particle size of the deformable liposomes ranged from 217.4 to 117.4 nm, depending on the composition. The entrapment efficiency was dependent on surfactant concentration and loading dose of arbutin. The permeation rate of 5% arbutin in deformable liposomes was $8.91({\pm}1.33){\mu}g/cm^2/h$, and was not significantly different from 5% arbutin aqueous solution $[9.82({\m}0.86){\mu}g/cm^2/h]$. The deposition of arbutin was $43.34({\pm}12.13)$ and $16.99({\pm}7.83){\mu}g/cm^2$ in stratum corneum layer and epidermis/dermis layer, respectively, after 12 h of permeation study. These results are consistent with several earlier studies for the localization effect of liposomal formulations in stratum corneum, and demonstrated the feasibility of the deformable liposomes as a promising carrier for the skin deposition of hydrophilic skin-whitening compounds.

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.241-247
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• 2008

Paclitaxel is a taxane diterpene amide, which was first extracted from the stem bark of the western yew, Taxus brevifolia. This natural product has proven to be useful in the treatment of a variety of human neoplastic disorders, including ovarian cancer, breast and lung cancer. Paclitaxel is a highly hydrophobic drug that is poorly soluble in water. It is mainly given by intravenous administration. Therefore, The pharmaceutical formulation of paclitaxel ($Taxol^{(R)}$; Bristol-Myers Squibb) contains 50% $Cremophor^{(R)}$ EL and 50% dehydrated ethanol. However the ethanol/Cremophor EL vehicle required to solubilize paclitaxel in $Taxol^{(R)}$ has a pharmacological and pharmaceutical problems. To overcome these problems, new formulations for paclitaxel that do not require solubilization by $Cremophor^{(R)}$ EL are currently being developed. Therefore this study utilized a supercritical fluid antisolvent (SAS) process for cremophor-free formulation. To select hydrophilic polymers that require solubilization for paclitaxel, we evaluated polymers and the ratio of paclitaxel/polymers. HP-${\beta}$-CD was used as a hydrophilic polymer in the preparation of the paclitaxel solid dispersion. Although solubility of paclitaxel by polymers was increased, physical stability of solution after paclitaxel/polymer powder soluble in saline was unstable. To overcome this problem, we investigated the use of surfactants. At 1/20/40 of paclitaxel/hydrophilic polymer/ surfactant weight ratio, about 10 mg/mL of paclitaxel can be solubilized in this system. Compared with the solubility of paclitaxel in water ($1\;{\mu}g/mL$), the paclitaxel solid dispersion prepared by SAS process increased the solubility of paclitaxel by near 10,000 folds. The physicochemical properties was also evaluated. The particle size distribution, melting point and amophorization and shape of the powder particles were fully characterized by particle size distribution analyzer, DSC, SEM and XRD. In summary, through the SAS process, uniform nano-scale paclitaxel solid dispersion powders were obtained with excellent results compared with $Taxol^{(R)}$ for the physicochemical properties, solubility and pharmacokinetic behavior.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.512-523
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• 2018

Background: 20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. Methods: MEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. Results: A Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient $r^2=0.929-0.947$). Conclusion: The MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

• Journal of Pharmaceutical Investigation
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• v.14 no.3
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• pp.122-130
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• 1984

The dissolution profiles of the seven branded prednisolone tablets were determined by means of available compendium. Those tablets were stored at $40^{\circ}C,\;50^{\circ}C\;and\;60^{\circ}C$ for 15, 30 and 60 days respectively. Under the stress conditions, the dissolution efficiency showed significant changes. It is considered that the determination of shelf life of drug from these aging effects is possible because the dissolution data followed a logarithmic distribution. There were no substantial differences of dissolution between two prednisolone formulations with different particle size not larger than $100\;{\mu}m$. The effect of two starches (corn and potato) on the rate of dissolution of prednisolone from dosage form was also investigated. All marketed tablets met the requirement of the established compendium.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.106-113
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• 2013

Background: For Korean pharmaceutical industry to continue to grow, it is requisite to enter the global markets of developed countries. However, the export volume has fallen short of 10% of the gross sales and the industry has only recently warming up to prepare the globalization along with suchlike the Columbus Project. Purpose: This research was conducted to identify the difficulties Korean pharmaceutical companies perceived and to discover the gap in the needs for the government aid the companies have been seeking in the purpose of entering the developed pharmaceutical markets. Method: A survey method was used for this research. Six experts were surveyed and provided comments for the pre-questionnaire. Then, a final questionnaire was developed consisting of 10 items on regulatory-related and another 10 items on non-regulatory-related factors in drug exportation using the Likert scale (1 to 5). The survey sample was 30 Korean companies which have participated in the Columbus Project since 2010. Results: Nineteen (63%) companies responded to the survey. Most companies perceived difficulty (mean = 4.19) over the entire pathway of the regulatory process of global markets. Clinical trials and post-marketing surveillance were remarked as the most difficult barrier to follow the regulatory globalization. Among non-regulatory related factors, marketing, arranging a distribution network, obtaining experts, and projecting a timeline in exportation were brought up as the most difficulty. Conclusion: Especially, cost and language barrier were considered as the main cause producing these difficulties across regulatory and non-regulatory processes and accordingly, securing both long term budget and experts at governmental level was suggested by the domestic pharmaceutical companies.

• Journal of Pharmaceutical Investigation
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• v.13 no.1
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• pp.23-35
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• 1983

Since the national health insurance was introduced in 1978, the increased utilization of hospitals and the growing importance of pharmaceutical services to hospital patients have made the administration of these services a very complex and specialized responsibility. The pharmaceutical services has always been an essential component of comtemporary hospital care. In the hospital, the pharmaceutical services is the professional department which concerns itself with the evaluation, selection, control and utilization of drugs. The director of this service must be a versatile professional person who can work effectively in a heterogenous society of educated persons. However, graduate education in hospital pharmacy has not been introduced yet in Korea. The necessity of graduate education hospital pharmacy has been discussed in this research. Graduate education in hospital pharmacy emphasizes preparation for assumption of responsibility as the senior hospital pharmacist or the director of pharmaceutical services. Graduates should also be prepared as administrators of a department that must operate with great efficiency. They should be prepared serve as a consultant on drugs for the medical and allied health professional staff, organizing and disseminating a large and dynamic body of information in their interest and to establish professional roles that emphasize procurement, storage, manufacturing, packaging, distribution, control and evaluation of drugs. Senior hospital pharmacist is a teacher charged with responsibility fer formal and informal instruction of other hospital personnel in pharmaceutical sciences. In addition, the graduates have the opportunity to be a researcher dealing with aspect of hospital care and are intensively educated in the professional aspects of hospital pharmacy practices. The curriculum of graduate education in hospital pharmacy should be established detailly and carefully to fit the educational objective.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.359-366
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• 2009

In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol$^{(R)}$ performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol$^{(R)}$, but the reduced release profile for PxLN-C. PxLN or Taxol$^{(R)}$ was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUC$_t$ of PxLN-H was 3.4-fold greater than that of Taxol$^{(R)}$. PxLN-H gave higher biodistribution in all tissues than did Taxol$^{(R)}$. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.

• Journal of Pharmaceutical Investigation
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• v.9 no.3
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• pp.9-21
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• 1979

This study was undertaken to establish the different pharmaceutical properties between promethazine HCl and promethazine pamoate. First, promethazine pamoate was prepared by using the modified method of Saias. Second, in order to study the different pharmacokinetics between promethazine pamoate and promethazine HCl, absorption rate, plasma concentration, and distribution, as well as urinary excretion of the both compounds were examined in rabbits as an experimental animal: The results were as follows. 1. In the in vitro isolated intestine of rabbit, the rate constant for absorption of promethazine pamoate was $0.347hr^{-1}$ and that of promethazine HCl was $0.532hr^{-1}$. 2. After oral administration of promethazine pamoate, the increase of plasma concentration of promethazine was much slower than that of promethazine HCl. 3. The urinary excretion rate of promethazine pamoate was significantly low in comparison to that of promethazine-HCl; i. e. about 50% of promethazine HCl was excreted within 3 hours, and 5 to 15 hours for that of promethazine pamoate. 4. The tissue concentration of promethazine after oral administration of promethazine pamoate in rabbit was steadily increased for 5 hours. However, promethazine HCl concentration reached to maximum 1 hour after administration, then decreased slowly. 5. A significant amount of promethazine was mainly distributed in spleen, kidney, lung, liver and heart in this order, rather than other organs, such as brain, and muscle. 6. In the toxicity test by using mouse, $LD_{50}$ for promethazine pamoate was 3,250 mg/kg, while $LD_{50}$ for promethazien HCl was 298mg/kg.

• Journal of Environmental Health Sciences
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• v.46 no.1
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• pp.45-64
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• 2020

Objectives: Limited information is available on the presence and associated ecological risks of pharmaceutical residues in aquatic environments near pharmaceutical manufacturing areas in Korea. In this study, we investigated the current state of pharmaceutical contamination and its associated ecological risks in streams near a pharmaceutical manufacturing complex. Methods: Seven pharmaceuticals (acetaminophen, clarithromycin, diclofenac, diphenhydramine, ibuprofen, mefenamic acid and roxithromycin) were measured in water samples collected from the streams near a pharmaceutical manufacturing complex. A predicted no-effect concentration (PNEC) was derived using either the assessment factor method or species sensitivity distribution method. In addition, a hazard quotient for each pharmaceutical was calculated by dividing its measured environmental concentration by its PNEC. Results: Samples collected downstream from the wastewater treatment plant (WWTP) had higher concentrations of pharmaceuticals than those collected from the reference site (upstream). Moreover, pharmaceutical concentrations were greater in ambient water than in the final effluent from the WWTP, which suggested that non-point sources were contributing to the contamination of the ambient water environment. Some of the target pharmaceuticals exhibited a hazard quotient >1, indicating that their potential ecological effects on the aquatic environment near the pharmaceutical industrial area should not be ignored. Conclusion: This study demonstrated that the pharmaceutical manufacturing area was contaminated with residual drugs, and that there was a possible non-point source near the WWTP effluent discharge area. The results of this study will aid in the development of management plans for pharmaceuticals, particularly in hotspots such as pharmaceutical industrial sites and their vicinities.

• Journal of Microbiology and Biotechnology
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• v.28 no.7
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• pp.1199-1208
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• 2018

Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized Clostridium butyricum) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of $10^8$ or $10^{10}CFU/day$ for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}l$ of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (i.e., COX-2, IL-6, $LTB_4$, and COMP), and significantly increased the concentration of $IFN-{\gamma}$ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (i.e., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ${\geq}20%$. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.