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양수근(Su Geun Yang),박준상(Jun Sang Park),최영욱(Young Wook Choi) 대한약학회 1995 약학회지 Vol.39 No.5
Solid lipid microspheres (SLMs) were prepared using various lipids and solidifying agents, in order to enhance the gastrointestinal absorption of Cyclosporine A (Cs A) which is a practically water-insoluble drug with low systemic bioavailability. Egg lecithin and HCO-60 (polyoxyethylated 60mol, hydrogenated castor oil) were used as lipids. Stearic acid and stearyl alcohol were used as solidifying agents. Emulsion concentrates containing Cs A were prepared by mixing the melted lipid and solidifying agent with water, employing bile salts as a cosurfactant. SLMs were obtained by dispersing the warm emulsion concentrate in cold distilled water under mechanical stirring, followed by freeze drying. Physical characteristics of each SLM were investigated by particle size analysis, optical microscopy and scanning electron microscopy. Mean particle size of SLMs was in the range of 30 to 40mcm. The SLMs were in good appearance with spherical shape before freeze drying, but were deformed partially after freeze drying. Drug loading efficiencies of SLMs were observed as high as 80 to 90% in average. The systemic bioavailability of Cs A from different SLM formula was investigated in rats following oral administration. Cs A in whole blood was extracted and assayed by HPLC. SLMs revealed the higher bioavailabilities than the standard formula based on the marketed product. SLMs might have several advantages over standard formula for enhanced gastrointestinal absorption, controlled release properties, high loading capacity of the water-insoluble drug, and feasibility of solid dosage forms with better stability in storage.
Pullulan으로 흡착코팅시킨 리포좀의 물리적 특성 및 담즙산염용액에서의 안정성
한양희,김상헌,양수근,최영욱 중앙대학교 약학연구소 1993 약학 논총 Vol.7 No.-
Liposomes have been used as drug carriers for the delivery of peptide, anticancer agent, hormones, and etc. Another possibiltity of liposome as an effective carrier for the oral administration of drugs which are unstable in gastrointestinal tract has been extensively studied in recent years, in the viewpoint of protection of liposome against pH, bile salts and pancreatic lipase in physiological circumstances. Pullulan, a hydrophilic polysaccharide and a coating agent for foods and drugs, was employed in this experiment to coat the DMPC liposomes (MLVs) by adsorption technique. Physical properties of pullulan-coated liposomes were investigated with TEM and particle size analyzer. Turbidity changes were measured and expressed as a relative turbidity (A_t/A_0), in order to compare the stability of uncoated or pullulan-coated liposomes against both pH shock and bile salts attack. The stability of liposomes was independent of pH, since turbidities of liposomes were unchanged for 8 hours in various pH buffer solutions from pH 1.2 to 7.4. On the other hand, from the observations in pH 5.6 or 6.8 buffer solution, pullulan-coated liposomes showed comparative stability against sodium choleate upto 0.15% concentration, although neither uncoated nor pullulan-coated liposomes revealed enough stability against the bile salt at 0.15% or higher concentration. Therefore, it is possible to conclude that pullulan-coated liposmes might be useful as a drug carrier for oral delivery, because of the enhanced stability in gastrointestinal environment. It is still necessary, however, to find out better selections for polymers and coating methods for the purpose of further stabilization of liposomes.
히드록시프로필셀룰로오스/카르보폴 고체분산체의 점막부착성과 팽윤 및 약물방출특성
김상헌,최영욱,양수근,신동선,이민석 한국약제학회 1994 Journal of Pharmaceutical Investigation Vol.24 No.3
Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing 300∼350g. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants, K_s and K_r respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.