• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.157-163
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• 2005

The pellets with multiple drug release system (MDRS) of Diltiazem. HCl which consist of immediate drug release layer, drug reservoir layer and controlled release rate membrane, were prepared by using CF-Coater. As main factors for more effective MDRS of Diltiazem. HCl, ethylcellulose was used for the controlling drug release rate, and diethylphthalate was used for plasticizer, respectively. In vitro evaluation study was performed by comparative dissolution test between our test MDRS and reference Diltiazem. HCl preparation. The physical tests were performed using FT-IR and SEM. In vivo evaluation was also performed by observing the behavior of a plasma drug concentration after oral administration. The bioavailability was determined by analyzing the blood sample after oral administration to healthy, male volunteers once a day. As a result, there were no significant differences in bioequivalence parameters $(AUC_{\infty},\;C_{max},\;t_{1/2})$ between two systems. It might be concluded that our MDRS of Diltiazem. HCl could be an alternative delivery system to reference drug preparation.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.177-183
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• 1998

Low toxicity, reverse thermal gelation and high drug loading capabilities suggest that poloxamer 407 gels have great potential as a topical drug delivery system. Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of skin irritancy due to its acidic pH. Poloxamer gels of different polymer contents were formulated to overcome the problem and compared to the cream type formulations of either w/o/w multiple emulsion cream or o/w type emulsion cream. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solutions. Drug release from w/o/w multiple emulsion cream was controlled by oil membrane, showing the apparent zero order release kinetics. The KA release from the poloxamer gels was also controlled by the gel matrix, showing that drug release increased linearly as KA contents increase, but decreased exponentially as the polymer contents increase. In the skin irritancy test, the primary irritancy index(PII) of poloxamer gel base was lower than those of multiple emulsion cream base and o/w cream. Depending on KA contents or polymer contents in the gel. PH values in poloxamer gels were ranged from 1.3 to 2.0, which are interpreted as low or negligible irritation on skin. There was a good correlation between the log value of flux in drug release and PII value in skin irritation. It was possible to conclude that the poloxamer gels containing KA might be a good candidate for an antimelanogenic topical delivery system by virtue of the controlled release of the drug and the reduced skin irritancy.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.87-92
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• 1998

Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of the skin irritancy and the instability against the pH, temperature, and light. In order to overcome these problems, various topical gels and multiple emulsion creams which can control the release of active ingredient, KA, were formulated employing cream bases of mineral oil with caprylic capric triglyceride and hydrophilic polymers such as chitosan, carbopol. and pluronics. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solution. Drug release from chitosan-based gels (ChitoGel) obeyed to the first order kinetics with a rapid release especially in the initial period. However, pluronic-based gels (PluGel) and carbopol-based gels (CarboGel) revealed controlled release of drug to some extent, followed by the square root-time kinetics. Moreover, the release of KA was further controlled with the W/O/W multiple emulsion creams (MultiCream), showing the apparent zero order release kinetics by virtue of dynamic ratecontrolling membrane of the oil layer. The flux $(J,\;{\mu}g/cm^2/hr)$ of ChitoGel. CarboGel. PluGel. and MultiCream in the initial period of 6hr were 73.30, 28.67. 24.04 and 7.72, respectively. On the other hand, the skin irritancy score of ChitoGel and MultiCream were observed as 2.5 and 2.3 respectively, in the rabbit skin irritation test. Although there were insignificant differences at p<0.05 between those formulations, it was possible to conclude that the W/O/W multiple emulsion creams containing KA might be a good candidate for an antimelanogenic drug delivery system due to the controlled release of acidic drug molecules.

• YAKHAK HOEJI
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• v.18 no.1
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• pp.49-58
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• 1974

Tablet product design problem was structured as constrained optimization problem and subsequently solved by multiple regression analysis and Lagrangian method of optimization. Aluminum flufenamate was the drug chosen and microcrystalline cellulose nad starch were the binder and disintegrant, respectivley. The effect of the binder and disintegrant concentration on tablet hardness, friability, volume, in vitro release rate, and urinary excretion rate of drug in human subjects was recorded. Since a reasonably rapid release rate of drug is generally an important objective in the design of solid dosage form, optimization of this parameter was employed in studying the applicability of constrained optimization to a pharmaceutical product design problem. In addition to finding optimal sitivity analysis studies to such problems was also illustratd. It would appear that prediction of the in vivo t$_{50%}$ response from a knowledge of the incitro t$_{50%}$ response can be made fairly accurately for the tablet system used in this study.

• Macromolecular Research
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• v.11 no.4
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• pp.207-223
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• 2003

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

• Elastomers and Composites
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• v.54 no.2
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• pp.149-155
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• 2019

Controlled mass transport in response to stimuli is essential for drug carriers. The complexity of the signaling system under physiological conditions has led researchers to develop precise nanocontainers that respond to stimuli in the physiological environment. Owing to several reasons, soft nanocontainers such as liposomes and micelles have been investigated for use as drug delivery systems. However, such carriers often suffer from the undesired leakage of drug molecules. In contrast, inorganic nanocontainers are robust, and their surfaces can be easily functionalized. For example, mesoporous silica nanoparticles equipped with gatekeeper molecules are increasingly being used for the controlled release of drug molecules in response to the desired stimuli. Since the development of the first hybrid nanocontainer comprising molecular machines, multiple versions of such gatekeeper systems featuring significantly improved stability and precise response to stimuli have been reported. In this study, various methods for incorporating photoresponsive nanocontainers with porous channels are developed.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.14 no.1
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• pp.3-11
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• 2003

Attention-deficit/Hyperactivity disorder(ADHD) is the most common psychiatric disorder of childhood and among the most prevalent chronic health conditions affecting school-aged children. Children with ADHD experience significant functional problems, such as school difficulties, academic underachievement, troublesome interpersonal relationships with family members and peers, and low self-esteem. The most widely used pharmacological treatments for ADHD are psychostimulants, such as methylphenidate and amphetamine salts. These medications provide clinical efficacy by increasing the availability of catecholamines, primarily dopamine, in the frontal lobe of the brain. immediate-release(IR) formulations of sychostimulants were among the most effective psychotrophic medications in the psychopharmacological treatment. However, there are some limitations of IR formulations：the short half-life and duration of efficacy, which result in the need for multiple daily dosing and the poor compliance. These limitations have led to the development of once-daily, extended-release(ER) formulations of methylphenidate and amphetamine salts. However, these ER formulations may not be as immediately helpful to ADHD children due to delayed onset of action and the acute tolerance which is the failure to sustain the efficacy with the same concentration of drug as the initial stage of medication. OROS-methylphenidate(Concerta$^{\circledR}$) given once a day produces an ascending-pattern plasma drug level generated by the osmotically released, timed drug-delivery system. These new formulations of the psychostimulants have been shown to be a useful alternative to old stimulant medications through the evidence by the clinical trials.

• Implantology
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• v.18 no.2
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• pp.120-138
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• 2014

Purpose: The purpose of this study was to review the outcomes of a series of studies on tissue regeneration conducted in multiple institutions including the Department of Periodontology, College of Dentistry, Yonsei University. Materials and Methods: Studies were performed divided into the following three subjects; 1) Development of three-dimensional nano-hydroxyapatite (n-HA) scaffold for facilitating drug release and cell adhesion. 2) Synergistic effects of bone marrow-derived mesenchymal stem cells (BMMSC) application simultaneously with platelet-rich plasma (PRP) on HA scaffolds. 3) The efficacy of silk scaffolds coated with n-HA. Also, all results were analyzed by subjects. Results: Hollow hydroxyapatite spherical granules were found to be a useful tool for the drug release and avidin-biotin binding system for cell attachment. Also, BMMSC simultaneously with PRP applied in an animal bone defect model was seen to be more synergistic than in the control group. But, the efficacy of periodontal ligament cells and dental pulp cells with silk scaffolds could not be confirmed in the initial phase of bone healing. Conclusion: The ideal combination of three elements of tissue engineering-scaffolds, cells and signaling molecules could be substantiated due to further investigations with the potentials and limitations of the suggested list of studies.