• Journal of Pharmaceutical Investigation
• /
• 제32권4호
• /
• pp.267-275
• /
• 2002

A self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and ultimately bioavailability of a poorly water soluble drug, lovastatin. SMEDDS was thε mixtures of oils, surfactants, and cosurfactants, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal (GI) tract. Various types of self-emulsifying formulations were prepared using four types of oil (Capryol 90, Lauroglycol 90, Labrafil M 1944 CS and Labrafil M 2125), two surfactants (Cremophor EL and Tween 80), and three cosurfactants (Carbitol, PEG 400 and propylene glycol). Thε efficiency of emulsification was studied using a laser diffraction size analyzer to determine particle size distributions of the resultant emulsions. Optimized formulations selected for bioavailability assessment were Carpryol 90 (40%), Cremophor EL (30%) and Carbitol (30%). SMEDDS containing lovastatin (20 mg and 5 mg) were compared to a conventional lovastatin tablet $(Mevacor^{\circledR},\;20\;mg/tab)$ by the oral administration as prefilled hard gelatin capsules to fasted beagle dogs for in vivo study. The arεa under the serum concentration-time curve from time zero to the last measured time in serum, $AUC_{0{\rightarrow}24h}$, was significantly greater in SMEDDS, suggesting that bioavailability increase 130% and 192% by the SMEDDS, respectively. The self-emulsifying formulations of lovastatin afforded the improvement in absolute oral bioavailability relative to previous data of lovastatin tablet formulation. These data indicate the utility of dispersed self-emulsifying formulations for the oral delivery of lovastatin and potentially other poorly absorbed drugs.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.230.1-230.1
• /
• 2003

In case of oral application of quinupramine, antidepressants, it may cause adverse effects such as diarrhea, nausea due to transient high blood concentration. Ethylene vinyl acetate (EVA) which is heat-processible, flexible, inexpensive material was used for transdermal drug delivery. The purpose of this study was to develop the new transdermal delivery system of quinupramine using EVA polymer matrix that can provide sustained release and avoid the side effects. The EVA matrix containing quinupramine was prepared by solvent-evaporation method. (omitted)

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제11권6호
• /
• pp.526-529
• /
• 2006

The aim of this study was to prepare cyclosporin A-loaded liposome (CyA-Lip) as an oral delivery carrier, with their encapsulation into microspheres based on alginate or extracellular polysaccharide (EPS) p-m10356. The main advantage of liposomes in the microspheres (LIMs) is to improve the restricted drug release property from liposomes and their stability in the stomach environment. Alginate microspheres containing CyA-Lip were prepared with a spray nozzle; CyA-Liploaded EPS microspheres were also prepared using a w/o emulsion method. The shape of the LIMs was spherical and uniform, and the particle size of the alginate-LIMs ranged from 5 to $10\;{\mu}m$, and that of the EPS-LIMs was about $100\;{\mu}m$. In a release test, release rate of CyA in simulated intestinal fluid (SIF) from the LIMs was significantly enhanced compared to that in simulated gastric fluid (SGF). In addition, the CyA release rates were slower from formulations containing the liposomes compared to the microspheres without the liposome. Therefore, alginate-and EPS-LIMs have the potential for the controlled release of CyA and as an oral delivery system.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제35권6호
• /
• pp.396-401
• /
• 2013

Chronic osteomyelitis is an infection and inflammation of the bone or bone marrow, causing ischemia in bone marrow due to lack of blood, nutrients, and oxygen supply to the bone marrow, eventually leading to necrosis of bone marrow. A current method for treatment of chronic osteomyelitis is administration of systemic antibiotics followed by removal of the infected bone and tissues. Because infected tissue of chronic osteomyelitis is surrounded by avascular necrotic bone, supply of blood and antibiotics to the infected area is diminished. For effective treatment, high plasma concentrations of antibiotics should be provided for a prolonged period. However, long term high serum level of antibiotics may result in undesirable adverse effects. For delivery of a sufficient concentration of antibiotic to the infected area while avoiding the adverse effect, implantation of a local antibiotic delivery system is suggested. One of the implantation systems that has been utilized is antibiotic impregnated polymethyl methacrylate.

• Journal of Pharmaceutical Investigation
• /
• 제37권6호
• /
• pp.339-347
• /
• 2007

SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal(GI) tract. The main purpose of this work is to prepare self-microemulsifying drug delivery system(SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, atorvastatin calcium. Solubility of atorvastatin calcium was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identity the efficient self-emulsification region and particle size distributions of the resultant micro emulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were $Capryol^{(R)}$ 90(50%), Tetraglycol(16%), and $Cremophor^{(R)}$ EL(32%). The release rate of atorvastatin from SMEDDS was significantly higher than the conventional tablet ($Lipitor^{(R)}$), 2-fold. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin calcium by the oral route.

• Journal of Preventive Medicine and Public Health
• /
• 제14권1호
• /
• pp.3-12
• /
• 1981

To identify the changes in professional care patterns after the introduction of medical insurance in Korea, professional care in hospitals and clinics of two succeeding years were compared. The hospitals and clinics selected for this study were those which located in Seoul city. Hospitals were classified into 3 categories: university hospital, general hospital and hospital. The diseases selected for this study were acute appendicitis and normal delivery. They were selected because their disease courses are considered to be fairly stable. The variables used for this study were length of stay, total hospital costs, costs of each components of cares. The information used for this study was obtained from the official forms requested by the medical facilities to the Korea Medical Insurance Corporation. The two periods studied were 3 months of each year from March 1st to May 31st in 1979 and 1980, The total number of normal delivery studied was 289 in 1979, 301 in 1980 respectively and the acute appendicitis was 92 and 111 respectively. In order to compare the quantity of medical care between 2 study periods the insurance price scores of 1979 were converted to prices of 1980. For statistical test of difference between 2 periods T-test and Welch's test were used. The result of the study were briefly summarized in below. 1. No significant difference was observed in the average length of stay of both disease between two study periods in all types of hospitals. 2. No significant difference was observed in the average total hospital costs of both diseases in all types of hospital, but in the private clinic the average clinic costs was rather decreased significantly in 1980. 3. More cost decrease were seen than cost increase in 1980 in all types of facilities, More cost changes by items were seen in acute appendicitis than in normal delivery between two study periods. The total hospital costs can be devided into 2 portions: charges for drug and material and for physician. In normal delivery, costs for physician's charges was significantly decreased in almost all the hospitals and costs for drug and material were not changed significantly in all the hospitals in 1980. In the university hospitals, however, the costs for drug and material were increased significantly in 1980. The cost decrease for physician's charge were mainly due to the decrease in the costs of laboratory test, treatment and physical therapy. The increase in the costs for the drug and material in the university hospitals was mainly due to the increase in the cost for drugs for oral administration and injection. 4. The proportion of components of medical care in the hospital has not been changed significantly, however, the cost for injection in normal delivery was characteristically increased in 1980 in all hospitals studied. In general the proportion of the costs for drug and material was tended to increase and the costs for physician was tended to decrease in 1980. The increase in the costs for drug and material were considered to be due to increase in the cost for drugs for oral administration and injection. The decrease in the costs for physician were due to decrease in the costs of laboratory test, treatment and physical therapy. Above mentioned changes in hospital and clinic care patterns are considered to be mostly influenced by the review criteria set by the K.I.C. for the assessment of the fee request made by clinics and hospitals.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제30권1호
• /
• pp.17-24
• /
• 2004

The purpose of this study was to evaluate the stability and efficacy of biologic membrane made of freeze-dried cartilage as a barrier to facilitate guided bone regeneration in experimental non-healing bone defects in the rat mandible. Nine adult Sprague-Dawley rats (400-500g) were used in experiment. 5.0mm in diameter were created on the mandibular angle area by means of slow-speed trephine drill. In microscopic examination, dynamic immature bone forming at 2 weeks and its calcification at 4 weeks were observed. The membrane made of lyophilized cartilage taken from human costal cartilage seems to be very effective for guided bone regeneration as a biologic membrane and the scaffold for attachment of cells or local drug delivery system of growth factor, which may meet the ideal requirement of a barrier membrane and graft materials.

• Journal of Pharmaceutical Investigation
• /
• 제35권6호
• /
• pp.445-451
• /
• 2005

As a selective ${\alpha}_{1A}-adrenoreceptor$ antagonist, tamsulosin has been used clinically for urinary obstructed patients with benign prostatic hyperplasia. The single and multi-layered pellets containing tamsulosin hydrochloride were prepared in an effort to control the drug release, avoiding dose-dependent side effects of tamsulosin hydrochloride upon oral administration. The drug release from multi-layered pellets was substantially controlled, compared with single layered pellets. The drug release from coated pellets with single or multi layer was affected by the nature of coating agent, the percentage of coating level and the presence of hydrophilic material in coating layer. In conclusion, the controlled release oral delivery system using multi-layered pellet is very useful for tamsulosin hydrochloride, resulting in improvement of patient compliance and therapeutic drug levels for a longer period of time.

• Journal of Pharmaceutical Investigation
• /
• 제37권4호
• /
• pp.237-242
• /
• 2007

The chemical formula of indapamide is 3-(aminosulfonyl)-4-chloro-N-(2,3-dihydro-2-methyl-1H-indol-l-yl)-benzamide, Indapamide is an oral antipertensive diuretic agent indicated for the treatment of hypertensive and edema. Indapamide inhibits carbonic anhydrase enzyme. Transdermal drug delivery systems, as compared to their corresponding classical oral or injectable dosage form counterparts, offer many advantages. The most important advantages are improved systemic bioavailability of the pharmaceutical active ingredients (PAI), because the first-pass metabolism by the liver and digestive system are avoided; and the controlled, constant drug delivery profile (that is, controlled zero-order absorption). Also of importance is the reduced dose frequency compared to the conventional oral dosage forms (that is, once-a-day, twice-a-week or once-a-week). Other benefits include longer duration of therapeutic action from a single application, and reversible action. For example, patches can be removed to reverse any adverse effects that may be caused by overdosing. In order to evaluate the effects of vehicles and penetration enhancers on skin permeation of Indapamide, the skin permeation rates of Indapamide from vehicles of different composition were determined using Franz cells fitted with excised hairless skins. Solubility of Indapamide in various solvents was investigated to select a vehicle suitable for the percutaneous absorption of Indapamide, The solvents used were Tween80, Tween20, Labrasol, Lauroglycol90 (LG90) and Peceol. Lauroglycol90 increase the permeability of indapamide approximately 3.75-fold compared with the control. Tween80, Tween20, Labrasol, Lauroglycol90 (LG90) and Peceol showed flux of $0.06ug/cm^2/hr,\;0.4ug/cm^2/hr,\;0.21ug/cm^2/hr,\;0.72ug/cm^2/hr,\;0.29ug/cm^2/hr$, respectively.

• Journal of Pharmaceutical Investigation
• /
• 제34권6호
• /
• pp.471-475
• /
• 2004

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.