• Proceedings of the KOSOMBE Conference
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• v.1996 no.11
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• pp.281-285
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• 1996

Pulsatile swelling behaviors and their application to drug delivery system were studied by using interpenetrating polymer networks(IPN) hydrogels constructed with poly(vinyl alcohol) and poly(acrylic acid). The PVA/PAAc IPNs hydrogels were symthesized by UV irradiation tallowed by repetitive freezing and thawing method. These hydrogels showed pH and temperature sensitive swelling behaviors. From the release experiment, the release amount of model drug incorporated into these hydrogels showed pulsatile patterns. Permeability coefficients obtained by various solutes differed in response to changes of permeation conditions.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.1-12
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• 2004

Initial burst is one of the major challenges in protein-encapsulated microparticle systems. Since protein release during the initial stage depends mostly on the diffusional escape of the protein, major approaches to prevent the initial burst have focused on efficient encapsulation of the protein within the microparticles. For this reason, control of encapsulation efficiency and the extent of initial burst are based on common formulation parameters. The present article provides a literature review of the formulation parameters that are known to influence the two properties in the emulsion-solvent evaporation/extraction method. Physical and chemical properties of encapsulating polymers, solvent systems, polymer-drug interactions, and properties of the continuous phase are some of the influential variables. Most parameters affect encapsulation efficiency and initial burst by modifying solidification rate of the dispersed phase. In order to prevent many unfavorable events such as pore formation, drug loss, and drug migration that occur while the dispersed phase is in the semi-solid state, it is important to understand and optimize these variables.

• Archives of Pharmacal Research
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• v.12 no.3
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• pp.191-195
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• 1989

The release of progesterone from monolithic devices composed of different ratios of polyethylene oxide (PEO; mw 20, 000) and hydrophobic polydimethylsiloxane was investigated. Water soluble PEO soaked into the polymer provided controlled release of progesterone. The release rate of progesterone could be controlled by varying the contents of PEO and progesterone in soaking solution. The progesterone release rate from silicone devices increased as the content of PEO in devices increased, while it decreased as the content of PEO in soaking solution increased. The release rate may be made by simple alterations of geometry of devices controlled swelling and the change in the physical structure of polymer network. Hydrophobic polydimethylsiloxane containing PEO and progesterone can provide a contraceptive material for prolonged release of progesterone.

• Journal of Korean Neurosurgical Society
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• v.63 no.1
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• pp.45-55
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• 2020

Objective : Fibrin sealants have been used for hemostasis, sealant for cerebrospinal fluid leakage, and adhesive barrier in neurosurgery. Further, as its clinical use and role of an effective drug delivery vehicle have been proposed. This study was performed to measure antibacterial activity and continuous local antibiotic release from different concentrations of vancomycin-impregnated fibrin sealant in vitro. Methods : Antibacterial activity was investigated by disk diffusion test by measuring the diameter of the growth inhibition zone of bacteria (methicillin-resistant Staphylococcus aureus, ATCC29213) from vancomycin-embedded fibrin sealant disc diluted at five different concentrations (C1-C5; 8.33, 4.167, 0.83, 0.083, and 0.0083 mg/disc, respectively). Continuous and conditioned release of vancomycin concentration (for 2 weeks and for 5 days, respectively) were also measured using high-performance liquid chromatography (HPLC) method. To mimic the physiologic wound conditions with in vitro, conditioned vancomycin release in phosphate buffer solution (PBS) was measured and replaced PBS for five consecutive days, half a day or completely daily. Results : In the disk diffusion test, the mean diameters of bacterial inhibition zone were 2.54±0.07 cm, 2.61±0.12 cm, and 2.13±0.15 cm (C1, C2, and C3 respectively) but 1.67±0.06 cm and 1.23±0.15 cm in C4 and C5, respectively. Continuous elution test elicited the peak release of vancomycin from the fibrin sealant at 48 hours, with continued release until 2 weeks. However, conditioned vancomycin release decreased to half or more on day 2, however, the sustainable release was measured over the therapeutic dose (10-20 ㎍/mL) for 5 days and 4 days in assays of half and total exchange of PBS. Conclusion : This study suggests that fibrin sealant can provide an efficient vehicle for antibiotic drug release in a wide range of neurosurgical procedures and the safe and effective therapeutic dose will be at the concentration embedded of 4.167 mg/disc or more of vancomycin.

• Polymer(Korea)
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• v.26 no.5
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• pp.691-700
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• 2002

Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

• Polymer(Korea)
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• v.34 no.3
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• pp.269-273
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• 2010

The primary objective of this work is to find the optimal condition for the granule tablet formulation of alfuzosin-HCl that aims to achieve a sustained drug release. (Hydroxypropyl)methyl cellulose (HPMC) is one of the most widely used polymer as a drug formulation and therefore has been utilized in this study as an excipient. Alfuzosin-HCl granule tablet was developed using the various viscosities of HPMC and the effects of viscosity on drug release was investigated. Fourier transform-infrared (FTIR) and X-ray diffraction (XRD) were employed to investigate the chemical structure and crystallization of alfuzosin-HCl in the formulation. We prepared the granule tablet by a direct compression method and studied the release profile in the stimulated intestinal fluid (pH 6.8). As the viscosity of HPMC increased the release of alfuzosin-HCl decreased, demonstrating that controlled release of alfuzosin-HCl can be achieved by varying the viscosity of HPMC.

• Polymer(Korea)
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• v.31 no.3
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• pp.201-205
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• 2007

Biodegradable polymers such as polylactide, polyglycolide and poly (lactide- co-glycolide) (PLGA) have been extensively investigated because of easily controlled drug release rate, completely degradable materials without the toxic by-product, and good biocompatibility. But, according to the bulk erosion property of PLGA in vitro test, it had the disadvantage that first-order release reduced releasing amount slowly after excessive initial burst. In this study we used PLGA powder obtained through recrystallization to revise bulk erosion property of PLGA. The PLGA used in this study was prepared by vacuum drying method and to estimate release profiles of BCNU loaded PLGA wafer. We also evaluated the release profile of drug with the water soluble additive. It was found that the drug loaded PLGA recrystallized by vacuum drying method exhibited the initial burst and the constant rate of drug release compared to that prepared by a conventional method.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.664-670
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• 1998

The role of intracellular $Ca^{2+}$, in the regulation of tumor cell proliferation by products of arachidonic acid (AA) metabolism was investigated using U-373 MG human as trocytoma cells. Treatment with nordihydroguaiaretic acid (NDGA), a lipoxygenase (LOX) inhibitor, or caffeic acid (CA), a specific 5-LOX inhibitor, suppressed proliferation of the tumor cells in a dose-dependent manner. However, indomethacin (indo), a cyclooxygenase (COX) inhibitor, did not significantly alter proliferation of the tumor cells. At anti-proliferative concentrations, NDGA and CA significantly inhibited intracellular $Ca^{2+}$ release induced by carbachol, a known intracelluar $Ca^{2+}$ agonist in the tumor cells. Exogenous administration of leukotriene $B_4(LTB_4)$, an AA metabolite of LOX pathway, enhanced proliferation of the tumor cells in a concentration-dependent fashion. In addition, $LTB_4$, induced intracelluar $Ca^{2+}$ release. Intracellular $Ca^{2+}$-inhibitors, such as an intracellular $Ca^{2+}$ chelator (BAPTA) and intracellular $Ca^{2+}$-release inhibitors (dantrolene and TMB-8), significantly blocked the LTB4-induced enhancement of cell proliferation and intracellular $Ca^{2+}$ release. These results suggest that LOX activity may be critical for cell proliferation of the human astrocytoma cells and that intracelluar $Ca^{2+}$ may play a major role in the mechanism of action of LOX.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.393-399
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• 2006

This study was aimed to design, formulate and characterize the moisture-activated patches containing acyclovir for antiviral action. Gel intermediates for film-type patches were prepared with mucoadhesive polymer, viscosity builders, enhancers and acyclovir. Patches containing acyclovir were characterized by in vitro measurement of drug release rates through a cellulose barrier membrane, and of drug flux through the hairless mouse skin. Film-type patches obtained were uniform in the thickness and showed a mucoadhesive property when contacted with moisture. The formulation was optimized, which consisted of $Cantrez^{\circledR}$ AN-169(2%), $Kollidon^{\circledR}$ VA 64(1%), $Natrosol^{\circledR}$(1%), hydroxypropyl-$\beta$-cyclodextrin(1%) and dimethylsulfoxide(0.5%). Release rates of acyclovir patches increased dose-dependently. The addition of terpenes such as d-limonene or cineole increased release rates of acyclovir, but decreased permeation rates. The permeation rates were enhanced by 2 and 2.5 times by the addition of glycyrrhizic acid ammonium salt and sodium glycocholate, respectively, compared with that of no enhancer. These results suggest that it may be feasible to deliver acyclovir through the skin or gingival mucosa from the moisture-activated patches.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.279-288
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• 2011

The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.