• Title/Summary/Keyword: Pharmaceutical solids

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Polymorphic Characterization of Pharmaceutical Solids, Donepezil Hydrochloride, by 13C CP/MAS Solid-State Nuclear Magnetic Resonance Spectroscopy

  • Park, Tae-Joon;Ko, Dong-Hyun;Kim, Young-Ju;Kim, Yon-Gae
    • Bulletin of the Korean Chemical Society
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    • v.30 no.9
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    • pp.2007-2010
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    • 2009
  • Donepezil hydrochloride is a reversible acetylcholinesterase inhibitor that is used in the treatment of Alzheimer’s disease to improve the cognitive performance. It shows different crystalline forms including hydrates. Therefore, it is very important to confirm the polymorphic forms in the formulations of pharmaceutical materials because polymorphs of the same drug often exhibit significant differences in solubility, bioavailability, processability and physical/chemical stability. In this paper, four different forms of donepezil hydrochloride were prepared and characterized using X-ray powder diffraction, Fourier transform infrared, and solid-state nuclear magnetic resonance (NMR) spectroscopy. This study showed that solid-state NMR spectroscopy is a powerful technique for obtaining structural information and the polymorphology of pharmaceutical solids.

Effect of Crystal Form on Bioavailability (결정형이 생체이용률에 미치는 영향)

  • Sohn, Young-Taek
    • Journal of Pharmaceutical Investigation
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    • v.34 no.6
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    • pp.443-452
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    • 2004
  • Habit is the description of the outer appearance of a crystal. If the environment of a growing crystal affects its external shape without changing its internal structure, a different habit results. Crystal habit and the internal structure of a drug can affect bulk and physicochemical properties, which range from flowability to chemical stability. A polymorph is a solid crystalline phase of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid state. Chemical stability and solubility changes due to polymorphism can have an impact on a drug's bioavailability and its development program. During crystallization from a solution, crystals separating may consist of a pure component or be a molecular compound. Solvates are molecular complexes that have incorporated the crystallizing solvent molecule in their lattice. When the solvent incorporated in the solvate is water, it is called a hydrate. To distinguish solvates from polymorphs, which are not molecular compounds, the term pseudopolymorph is used. Identification of possible hydrate compounds is important since their aqueous solubilities can be significantly less than their anhydrous forms. Conversion of an anhydrous compound to a hydrate within the dosage form may reduce the dissolution rate and extent of drug absorption. An amorphous solid may be treated as a supercooled liquid in which the arrangement of molecules is random. Amorphous solids lack the three-dimensional long-range order found in crystalline solids. Since amorphous forms are usually of higher thermodynamic energy than corresponding crystalline forms, solubilities as well as dissolution rates are generally greater. A study on crystal form includes characterization of (l)crystal habit, (2)polymorphism, (3)pseudopolymorphism, (4)amorphous solid.

Characterization of flow properties of pharmaceutical pellets in draft tube conical spout-fluid beds

  • Foroughi-Dahr, Mohammad;Sotudeh-Gharebagh, Rahmat;Mostoufi, Navid
    • Journal of Industrial and Engineering Chemistry
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    • v.68
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    • pp.274-281
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    • 2018
  • Experimental studies of the hydrodynamic performance of the draft tube conical spout-fluid bed (DCSF) were conducted using pharmaceutical pellets. The experiments were carried out in a DCSF consisted of two sections: (a) a conical section with the cross section of $120mm{\times}250mm$ and the height of 270 mm, (b) a cylindrical section with the diameter of 250 mm and the height of 600 mm. The flow characteristics of solids were investigated with a high speed camera and a pezoresistive absolute pressure transducer simultaneously. These characteristics revealed different flow regimes in the DCSF: packed bed at low gas velocities, fluidized bed in draft tube at higher gas velocities until minimum spouting, and spouted bed. The stable spouting was identified by the presence of two dominant frequencies of the power spectrum density of pressure fluctuation signature: (i) the frequency band 6-9 Hz and (ii) the frequency band 12-15 Hz. The pressure drops across the draft tube as well as the annulus measured in order to better recognize the flow structure in the DCSF. It was observed that the pressure drop across the draft tube, the pressure drop across the annulus, and the minimum spouting velocity increase with the increase in the height of draft tube and distance of the entrainment zone, but with the decrease in the distributor hole pitch. Finally, this study provided novel insight into the hydrodynamic of DCSF, particularly minimum spouting and stable spouting in the DCSF which contains valuable information for process design and scale-up of spouted bed equipment.

Physiochemical Properties and Antibacterial Activities of Metal Complexes of Norfloxacin (노르후록사신-금속이온 착물의 물리화학적 성질 및 항균력)

  • Park, Won-Bong;Kim, Kyung-Ah;Lee, Myung-Hwan;Lee, Dong-Sun;Rho, Dong-Yoon
    • YAKHAK HOEJI
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    • v.36 no.6
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    • pp.577-581
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    • 1992
  • Norfloxacin complexes of $Fe^{2+}$, $Cu^{2+}$ and $Al^{3+}$ have been prepared as solids. The stoichiometry of the complexes has been established. IR investigation indicates the metal-ligating sites in norfloxacin. The bioactivities of complexes all lower than that of norfloxacin. The solubilities and partition coefficients have been measured as a function of temperature. The data are used to evaluate the thermodynamic parameters ${\Delta}G$, ${\Delta}H$, ${\Delta}S$ for the solute transfer process and compared with the parent quinolone, norfloxacin. The existence of such complexes is discussed in the light of quinolone mode-of-action theories.

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Ecotoxicity Assessment of Industrial Effluent in Gyeonggi-do (경기지역 산업시설 방류수 생태독성 영향 평가)

  • Cho, Won-Sil;Kim, Sang-Hoon;Yang, Hyoung-Jae
    • Journal of Environmental Health Sciences
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    • v.37 no.2
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    • pp.113-123
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    • 2011
  • Objectives: Industrial development in Korea results in a rapid increase in the number of chemicals, some of which may be responsible for toxicity to aquatic ecosystems. In addition, the types of hazardous chemicals included in industrial effluents have gradually increased. Therefore, chemical analysis alone is not enough to assess ecological effects of toxic chemicals in wastewater. Methods: In response to new regulations as whole effluent toxicity (WET) tests for effluent discharge of 15 publicly owned treatment works (POTWs) and 25 industrial effluent treatment plants in Gyeonggi-do, which will be effective from 2011, a necessity of studies emerges that investigates toxicity levels. Results: In case of the public treatment plants, none of them had exceeded the criteria for ecotoxicity. As for individual wastewater discharge facilities, on the other hand, two types were found to exceed the criteria: pulp and paper manufacturing facilities and pharmaceutical manufacturing facilities. For the pulp and paper manufacturing facilities, monitoring results could not help determine the exact toxicant identification. However, Daphnia magna inhibition effect or death was found to leave white plums, suggesting that suspended solids treated and the polymer used in coagulant dose. In case of pharmaceutical manufacturing facilities, the general water quality parameters cannot affect Daphia magna. However, conductivity and salinity can have an effect to be 14,000 ${\mu}s/cm$, 8.1‰ by salts, respectively. Toxicity Identification Evaluation (TIE) and Toxicity Reduction Evaluation (TRE) procedures results appeared to be effective for identifying toxic compounds in $Cl^{-}$ and $SO_4^{2-}$. Conclusions: It is necessary to develop control measures for water treatment chemicals and salts used for processes such as coagulation in individual wastewater discharge facilities in order to achieve the goal to protect aquatic ecosystems in public waters.

Optimization and Pretreatment for Hot Water Extraction of Korean Deer (Cervus canadensis Erxleben) Velvet Antlers

  • Jang, Dong Wook;Ameer, Kashif;Oh, Jun-Hyun;Park, Mi-Kyung
    • Journal of Microbiology and Biotechnology
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    • v.30 no.8
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    • pp.1116-1123
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    • 2020
  • Velvet antler (VA) is a historically traditional medicinal supplement and is well known in Asian countries for its pharmaceutical and health benefits. The objectives for this study were to optimize the hot water extraction (HWE) of VA for the Korean VA industry, and to determine the most effective pretreatment method among microwave (MW), ultrasonication (US), and enzymatic (EZ) techniques. Using response surface methodology, optimum extraction temperatures and times were determined by central composite design configuration based on extraction yield and sialic acid content. Various quality parameters of VA extract including yield, soluble solid, protein, and sialic acid contents were also compared with the conjunction of HWE and pretreatment. The yield and sialic acid content of VA extract were determined to be 40% and 0.73 mg/g, respectively, under an optimum temperature of 100℃ at 24 h of extraction time. The yields from VA extracts pretreated with MW, US, and EZ were 17.42%, 19.73%, and 29.15%, respectively. Among the tested commercial enzymes, pepsin was the most effective proteolytic enzyme and led to the highest yield (47.65%), soluble solids (4.03 °brix), protein (1.12 mg/ml), and sialic acid (3.04 mg/ml) contents from VA extract.

Toxicity characteristics of sewage treatment effluents and potential contribution of micropollutant residuals

  • Kim, Younghee;Farnazo, Danvir Mark
    • Journal of Ecology and Environment
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    • v.41 no.11
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    • pp.318-327
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    • 2017
  • Background: A typical sewage treatment plant is designed for organic and nutrient removal from municipal sewage water and not targeted to eliminate micropollutants such as pesticides, pharmaceuticals, and nano-sized metals which become a big concern for sustainable human and ecological system and are mainly discharged from sewage treatment plant. Therefore, despite contaminant removal by wastewater treatment processes, there are still remaining environmental risks by untreated pollutants in STP (sewage treatment plant) effluents. This study performed aquatic toxicity tests of raw wastewater and treated effluents in two sewage treatment plants to evaluate toxicity reduction by wastewater treatment process and analyze concentration of contaminants to reveal potential toxic factors in STP effluents. Methods: Water samples were collected from each treatment steps of two STPs, and acute and chronic toxicity tests were conducted following USEPA (United States Environmental Protection Agency) and OECD (Organization for Economic Cooperation and Development) guidelines. Endpoints were immobility for mortality and reproduction effect for estrogenicity. Results: Acute $EC_{50}s$ (median effective concentration) of influents for Seungki (SK) and Jungnang (JN) STPs are $54.13{\pm}32.64%$ and $30.38{\pm}24.96%$, respectively, and reduced to $96.49{\pm}7.84%$ and 100%. Acute toxicity reduction was clearly correlated with SS (suspended solids) concentration because of filter feeding characteristics of test organisms. Chronic toxicity tests revealed that lethal effect was reduced and low concentration of influents showed higher number of neonates. However, toxicity reduction was not related to nutrient removal. Fecundity effect positively increased in treated wastewater compared to that in raw wastewater, and no significant differences were observed compared to the control group in JN final effluent implying potential effects of estrogenic compounds in the STP effluents. Conclusions: Conventional wastewater treatment process reduced some organics and nutritional compounds from wastewater, and it results in toxicity reduction in lethal effect and positive reproductive effect but not showing correlation. Unknown estrogenic compounds could be a reason causing the increase of brood size. This study suggests that pharmaceutical residues and nanoparticles in STP effluents are one of the major micropollutants and underline as one of estrogenic effect factors.

Selection of Optimum System in Constructed Wetlands for Treating the Hydroponic Waste Solution Containing Nitrogen and Phosphorus (질소 및 인 함유 폐양액 처리를 위한 최적 인공습지 시스템 선정)

  • Park, Jong-Hwan;Seo, Dong-Cheol;Kim, Seong-Heon;Lee, Choong-Heon;Choi, Jeong-Ho;Kim, Hong-Chul;Lee, Sang-Won;Ha, Yeong Rae;Cho, Ju-Sik;Heo, Jong-Soo
    • Korean Journal of Soil Science and Fertilizer
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    • v.45 no.5
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    • pp.764-771
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    • 2012
  • In order to develop constructed wetlands for treating hydroponic wastewater in greenhouse, actual constructed wetlands were used the obtained optimum condition in previous study, and the removal rate of pollutant in the water according to 4 kinds connection method of piping such as system A (UP-UP stream), system B (UP-DOWN system), system C (DOWN-UP stream) and system D (DOWN-DOWN stream) were investigated. Removal rate of biochemical oxygen demand (BOD), chemical oxygen demand (COD), suspended solids (SS), total nitrogen (T-N) and total phosphorus (T-P) by system A (UP-UP stream) connection method in actual constructed wetlands were slightly higher than other systems. At the system A, the removal rate of BOD, COD, SS, T-N and T-P were 88, 77, 94, 54 and 94%, respectively. Under different hydroponic wastewater loading, the removal rates of pollutants were higher in the order of $75L\;m^{-2}day^{-1}{\fallingdotseq}150L\;m^{-2}day^{-1}$ $$\geq_-$$ $300L\;m^{-2}day^{-1}$. Therefore, optimum connection method was system A for treating hydroponic wastewater in greenhouse.

Quality Properties Depending on Aging of Deabong Persimmon-fermented Liquor (매실 첨가 대봉감 발효 숙성주의 이화학적 특성)

  • Kwang Keun, Cho;Sang Won, Gal;Sang-Won, Lee
    • Journal of Life Science
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    • v.32 no.11
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    • pp.847-854
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    • 2022
  • The purpose of this study was to prepare Daebong persimmon-fermented liquor supplemented with Prunus mume fruit to promote the consumption of Daebong persimmon and to develop local specialties. As fermentation progressed, the alcohol content rapidly increased, whereas the sugar content decreased. With the production of CO2 from the second day of fermentation, the epidermis and flesh solids of the Daebong persimmons began mixing together and rose to the surface of the fermentation container. This phenomenon continued until the fourth and fifth days of fermentation; on the fifth day, the ethanol and sugar contents were 11.4% and 9.8°Brix, respectively. A concentration of 6 to 9% (w/w) P. mume fruit was found to be the optimal amount during Daebong persimmon fermentation. When the fermented liquor was stored for 60 days at 5℃, the pH and ethanol content showed no significant change during the aging period. As aging progressed, the content of sugar slowly decreased in both the control sample and in the one to which P. mume was added, showing 9.8 and 10.4 mg/ml at the eighth week post-aging, respectively. The total acid content was 0.79~0.81% at the beginning of aging but slightly increased to 0.84~0.86% in the second week of aging. As a result of the sensory test, the sour taste, sweetness, and flavor were slightly stronger in the P. mume fruit group than in the control group.