• 제목/요약/키워드: Dissolution Rate

검색결과 615건 처리시간 0.028초

고분자를 이용한 파모티딘 매트릭스 정의 용출에 관한 연구 (Studies on the Dissolution of the Famotidine Matrix Tablets using Polymer)

  • 최건혁;한상수;손동환;김재백
    • Journal of Pharmaceutical Investigation
    • /
    • 제24권3호
    • /
    • pp.139-144
    • /
    • 1994
  • The effect of some formulation variables on the release rate of famotidine, a $H_2$ receptor antagonist, from cellulose matrices containing hydroxypropylcellulose (HPC) in different ratios and types was investigated. The effects of tablet shape and compression pressure on dissolution rate of famotidine were studied. And the effect of the pH of dissolution media was also studied. Increase in the ratio of polymer to drug decreased the release rate of famotidine. Increase of the polymer viscosity also decreased the release rate. The release rate of famotidine was dependent on the pH of dissolution media. The release rate of drug was not much dependent on the compression pressure but dependent on the tablet shape and/or surface area. Consequently, the release rate of famotidine can be modified by changing the HPC contents, types of polymers with different viscosity grades or using appropriate fillers.

  • PDF

Preparation and Evaluation of Novel Fenofibrate-loaded Self-Microemulsifying Drug Delivery System (SMEDDS)

  • Cho, Young-Dae;Park, Young-Joon
    • Journal of Pharmaceutical Investigation
    • /
    • 제40권6호
    • /
    • pp.339-345
    • /
    • 2010
  • Fenofibrate has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood. However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery systems (SMEDDS). We used pseudo-ternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution assessment consisted of Lauroglycol FCC (60%), Solutol HS 15 (27%), and Transcutol-P (13%). The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was about 130 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

아세트아미노펜 좌제의 용출과 직장흡수 (Dissoultion and Rectal Absorption of Acetaminophen from Suppositories)

  • 한정선;심창구;김신근
    • 약학회지
    • /
    • 제31권5호
    • /
    • pp.286-295
    • /
    • 1987
  • The relationship between in vitro release and in vivo bioavailability of acetaminophen from suppositories was investigated. Effect of glycyrrhizin on the drug release and rectal absorption in rats was also examined. Suppositories containing 25mg of acetaminophen were prepared with Wecobee FS (fatty base) or PEG (water-soluble base) bases. The release from the suppositories were determined with USP rotating basket dissolution apparatus and with the suppository release tester. The temperature of the dissolution medium was very critical for the dissolution of acetaminophen from Wecobee FS suppositories. The bioavailability of acetaminophen was calculated from the plasma concentration-time curve after rectal administration of the suppositories to the rats. There were no significant differences in AUC following rectal administration of Wecobee FS and PEG suppositories, but the release and absorption from the Wecobee FS suppositories were faster than those from PEG suppositories. The dissolution rate obtained by the suppository release tester was better correlated with in vivo absorption rate constant than that by the USP dissolution apparatus. It suggests that the partitioning between rectal fluid and suppository base is the rate-limiting step in the rectal absorption of acetaminophen from suppositories. Glycyrrhizin was found not to affect in vitro dissolution and rectal absorption of acetaminophen.

  • PDF

Dissolution Characteristics of Hydrophobic Drug-Soluble Carrier Coprecipitates(III) -Dissolution Behaviour of Indomethacin from Several Fast Release Solid Dispersions of Indomethacin-

  • 전인구;이민화;김신근
    • Journal of Pharmaceutical Investigation
    • /
    • 제6권3호
    • /
    • pp.58-69
    • /
    • 1976
  • It is well established that dissolution is freruently the rate limiting step in the gastrointestinal absorpton of a drug from a solid dosage from. The relationship between the dissolution rate and absorption is particularly distinct when considering drugs of low solubility. Consequently, numerous attempts have been made to modify the dissolution characteristics of poorly water soluble drugs. Since dissolution rate is directly proportional to surface area, one may increase the rate by decreasing the particle size of the drug. Levy has considered a number of methods by which a drug may be presented to the GI fludids in finely divided from. The direct method is the utilization of microcrystalline or micronized particles. A second method involves the administration of solutions from which, upon dilution with gastric fluids, the dissolved drug will precipitate in the form of very fine particles. A more unique way of obtaining microcrystalline dispersions of a drug has been ercently suggested by Sekiguchi et al. They have first proposed the formation of a eutectic mixture of a poorly water soruble drug with a physiologically inert, easily soluble carrier. When such systems are exposed to water or GI fluids, the soluble carrier will dissolve rapidly and the finely dispersed drug particles will then be released. It has been suggested by Shefter and Higuchi that the formation of crystalline solvate could be a powerful tool in affecting rapid disslution of highly insoluble substances. Goldberg et al. have noted that the formation of solid solution could reduce the particle size to a minimum and increase the dissolution rate as well as the solubility of the durgs. It has also been shown that the rates of solution of drugs were appreciably increased by coprectipitating the drug with soluble polymers. The increase was found to be sensitive to the method of preparation, the molecular weight of polymer and the particular ratio of drugs to polymer. Although several investigations have demontrated that the solubility and/or dissolution rates of drugs can be increased in this manner, little information is available in the literature related to the in vivo absorption pattern of drugs orally administered as PVP coprecipitates. Recently, however, it was demonstrated that both the rate and extent of absorption of the insoluble drug could be markedly enhanced when orally administered to rats in the form of a coprecipitate with PVP. The purpose of the present investigation was to ascertain the general appility of soluble polymer coprectation technique as a method for enhancing the in vitro dissolution rate of hydrophobic indomethacin. To accomplish this aim, the dissolution characteristics of pure indomethacin, indomethcin-polymer physical mixtures and indomethacin-polymer coprecipitates were quantitatively studied by comparing their relative dissolution rates. The solubility and dissolution behavior of these systems were also examined.

  • PDF

Piperacillin Monohydrate Polymorphs의 용출속도(溶出速度)에 관(關)한 연구(硏究) (The Study on Dissolution Rate of Polymorphs of Piperacillin Monohydrate)

  • 김종갑;어경남
    • Journal of Pharmaceutical Investigation
    • /
    • 제15권4호
    • /
    • pp.186-197
    • /
    • 1985
  • Polymorphs of piperacillin monohydrate were prepared by various sedimentation methods from piperacillin base for the purpose of developing piperacillin preparations for oral use. Solubility and dissolution rate of each form of the polymorphs were compared with each other. It was found that Form IV showed the highest solubility and the fastest dissolution rate among four forms of polymorphs. In general, the solubility and dissolution rate of two amorphous forms, Form IV and II were higher than those of two crystal forms, Form I and III. The apparent dissolution rates in the artificial gastric juice within 60 minutes were $0.65{\times}10^{-6}mole{\cdot}min^{-1}\;cm^{-2}$ for From IV, $0.36{\times}10^{-6}mole{\cdot}min^{-1}{\cdot}cm^{-2}$ for From II, $0.30{\times}10^{-6}mole{\cdot}min^{-1}{\cdot}cm^{-2}$ for From III and $0.18{\times}10^{-6}mole{\cdot}min^{-1}{\cdot}cm^{-2}$ for From I, respectively.

  • PDF

Studies on Hydrophobic Drug-Soluble Carrier Coprecipitates(1)

  • Shin, Sang-Chul
    • Archives of Pharmacal Research
    • /
    • 제2권1호
    • /
    • pp.35-47
    • /
    • 1979
  • In order to increase the dissolution rate of furosemide(4-choro-N-furfury1-5-sulfamoy1 anthranilic acid_, various ratio coprecipitates with water-soluble polymers, such as polyvinylpyrrolidone and polythylene glycol, of different molecular weight, were prepared and quantitatively studied by comparing their dissolution characteristics of furosemide at powder state and at nondisintegrating disk state containing constant surface area at various temperatures and rotating velocities. The dissolution characteristics of furosemide from pure furosemide disks and 1:2(w/w) furosemide-PVP coprecipitate disks were in accordance with Noyes-Nernst equation and the rate constant of dissolution was proportional to the square root of rotating velocity of the disks. The intrinsic rate of dissoluton at 150 rpm, 37.deg.C was $2.21{\times}10^{-7}$ for the PVP 10, 000 COPRECIPITATE, $1.64{\times}10^{-7}$ for the PVP 40, 000 coprecipitate, and$ 1.44 {\times} 10^{-7}$for the PVP 360, 000 corprecipitate, while the rate was $1.27{\times}10^{-8}M/cm^{2} min$ for pure furosemide, repectively. The activation energy of dissolution was about 17, 000 for furosemide and about 7, 300 cal/mole for the 1:2 furosemide PVP 40, 000 coprecipitate, respectively.

  • PDF

지중저장 이산화탄소의 누출이 천부환경에서 방연석의 용해 과정에 미치는 영향 (The Effects of CO2 Released from Deep Geological Formations on the Dissolution Process of Galena in Shallow Subsurface Environments)

  • 남지은;왕수균
    • 한국지하수토양환경학회지:지하수토양환경
    • /
    • 제20권1호
    • /
    • pp.19-27
    • /
    • 2015
  • If $CO_2$ stored for geological sequestration escapes from deep formations and is introduced to shallow aquifers, it dissolves into groundwater, creates acidic environments, and enhance mineral dissolution from rocks and soils. Among these minerals, dissolution and spread of hazardous trace metals can cause environmental problems with detrimental impacts on groundwater quality. This study aims to investigate geochemical effects of $CO_2$ in groundwater on dissolution of galena, the main mineral controlling the mobility of lead. A series of batch experiments are performed with granulated galena in $CO_2$ solutions under various experimental conditions for $CO_2$ concentration and reaction temperature. Results show that dissolution of galena is significantly enhanced under acidic environments so that both of equilibrium concentrations and dissolution rates of lead increase. For thermodynamic analysis on galena dissolution, the apparent rate constants and the activation energy for galena dissolution are calculated by applying rate law to experimental results. The apparent rate constants are $6.71{\times}10^{-8}mol/l{\cdot}sec$ at $15^{\circ}C$, $1.77{\times}10^{-7}mol/l{\cdot}sec$ at $25^{\circ}C$, $3.97{\times}10^{-7}mol/l{\cdot}sec$ at $35^{\circ}C$ and the activation energy is 63.68 kJ/mol. The galena dissolution is suggested to be a chemically controlled surface reaction, and the rate determining step is the dissociation of Pb-S bond of surface complex.

Effects of Temperature and Pressure on Quartz Dissolution

  • Choi, Jung-Hae;Chae, Byung-Gon;Kim, Hye-Jin
    • 지질공학
    • /
    • 제25권1호
    • /
    • pp.1-8
    • /
    • 2015
  • Deep geological disposal is the preferred storage method for high-level radioactive waste, because it ensures stable long-term storage with minimal potential for human disruption. Because of the risk of groundwater contamination, a buffer of steel and bentonite layers has been proposed to prevent the leaching of radionuclides into groundwater. Quartz is one of the most common minerals in earth's crust. To understand how deformation and dissolution phenomena affect waste disposal, here we study quartz samples at pressure, temperature, and pH conditions typical of deep geological disposal sites. We perform a dissolution experiment for single quartz crystals under different pressure and temperature conditions. Solution samples are collected and the dissolution rate is calculated by analyzing Si concentrations in a solution excited by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). After completing the dissolution experiment, deformation of the quartz sample surfaces is investigated with a confocal laser scanning microscope (CLSM). An empirical formula is introduced that describes the relationship between dissolution rate, pressure, and temperature. These results suggest that bentonite layers in engineering barrier systems may be vulnerable to thermal deformation, even when exposed to higher temperatures on relatively short timescales.

Glass Dissolution Rates From MCC-1 and Flow-Through Tests

  • Jeong, Seung-Young
    • 한국방사성폐기물학회:학술대회논문집
    • /
    • 한국방사성폐기물학회 2004년도 학술논문집
    • /
    • pp.257-258
    • /
    • 2004
  • The dose from radionuclides released from high-level radioactive waste (HLW) glasses as they corrode must be taken into account when assessing the performance of a disposal system. In the performance assessment (PA) calculations conducted for the proposed Yucca Mountain, Nevada, disposal system, the release of radionuclides is conservatively assumed to occur at the same rate the glass matrix dissolves. A simple model was developed to calculate the glass dissolution rate of HLW glasses in these PA calculations [1]. For the PA calculations that were conducted for Site Recommendation, it was necessary to identify ranges of parameter values that bounded the dissolution rates of the wide range of HLW glass compositions that will be disposed. The values and ranges of the model parameters for the pH and temperature dependencies were extracted from the results of SPFT, static leach tests, and Soxhlet tests available in the literature. Static leach tests were conducted with a range of glass compositions to measure values for the glass composition parameter. The glass dissolution rate depends on temperature, pH, and the compositions of the glass and solution, The dissolution rate is calculated using Eq. 1: $rate{\;}={\;}k_{o}10^{(ph){\eta})}{\cdot}e^{(-Ea/RT)}{\cdot}(1-Q/K){\;}+{\;}k_{long}$ where $k_{0},\;{\eta}$ and Eaare the parameters for glass composition, pH, $\eta$ and temperature dependence, respectively, and R is the gas constant. The term (1-Q/K) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_{0},\;{\eta}\;and\;E_{a}$ are the parameters for glass composition, pH, and temperature dependence, respectively, and R is the gas constant. The term (1-Q/C) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_0$, and Ea are determined under test conditions where the value of Q is maintained near zero, so that the value of the affinity term remains near 1. The dissolution rate under conditions in which the value of the affinity term is near 1 is referred to as the forward rate. This is the highest dissolution rate that can occur at a particular pH and temperature. The value of the parameter K is determined from experiments in which the value of the ion activity product approaches the value of K. This results in a decrease in the value of the affinity term and the dissolution rate. The highly dilute solutions required to measure the forward rate and extract values for $k_0$, $\eta$, and Ea can be maintained by conducting dynamic tests in which the test solution is removed from the reaction cell and replaced with fresh solution. In the single-pass flow-through (PFT) test method, this is done by continuously pumping the test solution through the reaction cell. Alternatively, static tests can be conducted with sufficient solution volume that the solution concentrations of dissolved glass components do not increase significantly during the test. Both the SPFT and static tests can ve conducted for a wide range of pH values and temperatures. Both static and SPFt tests have short-comings. the SPFT test requires analysis of several solutions (typically 6-10) at each of several flow rates to determine the glass dissolution rate at each pH and temperature. As will be shown, the rate measured in an SPFt test depends on the solution flow rate. The solutions in static tests will eventually become concentrated enough to affect the dissolution rate. In both the SPFt and static test methods. a compromise is required between the need to minimize the effects of dissolved components on the dissolution rate and the need to attain solution concentrations that are high enough to analyze. In the paper, we compare the results of static leach tests and SPFT tests conducted with simple 5-component glass to confirm the equivalence of SPFT tests and static tests conducted with pH buffer solutions. Tests were conducted over the range pH values that are most relevant for waste glass disssolution in a disposal system. The glass and temperature used in the tests were selected to allow direct comparison with SPFT tests conducted previously. The ability to measure parameter values with more than one test method and an understanding of how the rate measured in each test is affected by various test parameters provides added confidence to the measured values. The dissolution rate of a simple 5-component glass was measured at pH values of 6.2, 8.3, and 9.6 and $70^{\circ}C$ using static tests and single-pass flow-through (SPFT) tests. Similar rates were measured with the two methods. However, the measured rates are about 10X higher than the rates measured previously for a glass having the same composition using an SPFT test method. Differences are attributed to effects of the solution flow rate on the glass dissolution reate and how the specific surface area of crushed glass is estimated. This comparison indicates the need to standardize the SPFT test procedure.

  • PDF

용융법에 의한 수용성 유리의 제조 및 특성 (I) : 용해 특성, 살균 효과 및 세포 독성 (Preparation and Characterization of Water-Soluble Glass through Melting Process (I) : Dissolution Characteristics, Bactericidal Effects and Cytotoxicity)

  • 조종호;이용근;최세영;신철수;김경남
    • 한국세라믹학회지
    • /
    • 제32권10호
    • /
    • pp.1093-1102
    • /
    • 1995
  • Water-soluble phosphate glasses containing Ag or Cu ion were prepared through melting process. Then the powdered glass samples were dissolved in D.I. water at room temperature with changing the dissolution time. In terms with the glass composition, dissolution characteristics, bactericidal effects and cytotoxicities were investigated. Dissolved amounts increased uniformly with dissolution time, and the dissolution rate was higher for ternary glass than for binary glass and with less metal oxide amount. And the dissolution rate of the glass with Ag ion was higher than that with Cu ion, and the bactericidal effect of the glass with Ag ion was also greater. Solution with more than 25 ppm of Ag was observed to have strong cytotoxicity to L929, and solutions of lower Ag concentration or with Cu seemed to have little cytotoxicity.

  • PDF