• Title/Summary/Keyword: Oral delivery system

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Relative Bioavailability and Pharmacokinetics of Newly Designed Cyclosporin A Self-microemulsifying Formulation after Single and Multiple Doses to Dogs

  • Yang, Su-Geun;Shin, Hee-Jong
    • Journal of Pharmaceutical Investigation
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    • v.39 no.2
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    • pp.111-115
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    • 2009
  • The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.

Dissolution of Chlorpheniramine Mallate (CMP) from Sustained-Release Tablets Containing CPM in the Coated Film Layer (핵정(核鐘)에 코팅된 필름층 중에 함유되어 있는 말레인산클로르페니라민의 방출특성)

  • Yu, Jei-Man;Shim, Chang-Koo;Lee, Min-Hwa;Kim, Shin-Keun
    • Journal of Pharmaceutical Investigation
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    • v.20 no.2
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    • pp.89-95
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    • 1990
  • Ethylcellulose-PEG 4000 film coated on core tablets was investigated as a potential drug delivery system for the controlled release of chlorpheniramine maleate (CPM). The kinetic analysis of the release data indicated that CPM release followed a diffusion-controlled model, where the quantity released per unit area is proportional to the square root of time. The effect of the film composition, CPM concentration, plasticizer concentration and CPM solubility on the release characteristics were examined. The release rate constant increased as CPM concentration increased. It also increased as the PEG 4000 content in the film increased above 10%(w/w), however, it decreased as the PEG 4000 content increased in the concentration range below 10%(w/w). The release rate constant was not affected by the coated weight on the core tablet. The film-coated tablets which contain CPM only in the coated film layer seemed to be a potential oral drug delivery system for the controlled release of CPM.

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A Study for Direct Application of Drug on Oral Mucosa (구강점막에서 약물의 직접적용을 위한 연구)

  • Jeong, Sung-Hee;Ok, Soo-Min;Huh, Joon-Young;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.35 no.4
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    • pp.229-235
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    • 2010
  • A common method for treating oral mucosal diseases is taking medication by oral administration. The oral administration is the method of least resistance. Because large part of drugs is degraded by liver, it is necessary to take more drugs getting to appropriate level in blood stream. And there are so many side effects when patients take drugs by oral administration. In so many cases, the patients who suffer from oral mucosal problems have the other general diseases simultaneously. Willingly or not, some patients can't take the medicine by oral administration. Number of topical drugs for oral mucosal disease is less than that for skin diseases because the environment of oral mucosa prevents activity of medicine. In this paper, research on effects of topical type medication for treating oral mucosal diseases is conducted through investigating currently used medications and their effects. In addition, effects of dissolved oral medications with appropriate solvent are demonstrated if this medication is useful for patients clinically.

Preparation of Alginate/Chitosan Microcapsules and Enteric Coated Granules of Mistletoe Lectin

  • Lyu, Su-Yun;Kwon, Young-Ju;Joo, Hye-Jin;Park, Won-Bong
    • Archives of Pharmacal Research
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    • v.27 no.1
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    • pp.118-126
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    • 2004
  • The aqueous extract of European mistletoe (Viscum album, L.) has been used in cancer therapy. The purified mistletoe lectins, main components of mistletoe, have demonstrated cytotoxic and immune-system-stimulating activities. Korean mistletoe (Viscum album L. coloratum), a subspecies of European mistletoe, has also been reported to possess anticancer and immunological activities. A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. coloratum agglutinin, VCA) with Mr 60 kDa was isolated from Korean mistletoe. Mistletoe preparations have been given subcutaneously due to the low stability of lectin in the gastrointestinal (GI) tract. In the present study, we investigated the possibility of alginate/chitosan microcapsules as a tool for oral delivery of mistletoe lectin. In addition, our strategy has been to develop a system composed of stabilizing cores (granules), which contain mistletoe lectin, extract or powder, coated by a biodegradable polymer wall. Our results indicated that successful incorporation of VCA into alginate/chitosan microcapsules has been achieved and that the alginate/chitosan microcapsule protected the VCA from degradation at acidic pH values. And coating the VCA with polyacrylic polymers, Eudragit, produced outstanding results with ideal release profiles and only minimal losses of cytotoxicity after manufacturing step. The granules prepared with extract or whole plant produced the best results due to the stability in the extract or whole plant during manufacturing process.

The Effect of Enhancer on the Penetration of Indapamide through Hairless Mouse Skin (경피흡수촉진제의 영향에 따른 인다파마이드의 피부투과)

  • Seo, Hui;Jeung, Sang-Young;Park, Ji-Seon;Shin, Byung-Cheol;Hwang, Sung-Joo;Cho, Sun-Hang
    • Journal of Pharmaceutical Investigation
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    • v.37 no.4
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    • pp.237-242
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    • 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.

Enhanced Iontophoretic Delivery of Risedronate Sodium Across Hairless Mice Skin (무모생쥐 피부에 리제드로네이트 소디움의 이온토포레시스 경피전달)

  • Hwang, In-Young;Lee, Mi-Jung;Jung, Suk-Hyun;Jeong, Seo-Young;Cho, Sun-Hang;Gil, Young-Sig;Jeong, Sang-Young;Shin, Byung-Cheol
    • Journal of Pharmaceutical Investigation
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    • v.40 no.2
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    • pp.79-84
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    • 2010
  • Osteoporosis was traditionally defined by the occurrence of nontraumatic fractures, especially of the spine, in the setting of low bone mass. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. Risedronate sodium is a bisphosphonate class used by oral formulation. In this study, risedronate was transdermally delivered by iontophoresis. Effects of polarity, pH, current density, and drug concentration were studied using a side-by-side diffusion cell including the hairless mice skin. In addition we studied effect of enhancers. The flux was evaluated by HPLC/UV system. The amount of transported drug under iontophoretic delivery was approximately 186 fold higher than that under passive delivery. Flux was proportional to the increase of drug concentration and current density. The flux was observed about 0.68mg/$cm^2$ when the amout of Propyleneglycol monolaurate (PGML) used 1% as enhancer. Results indicated that iontophoresis is an effective method for transdermal administration of risedronate sodium

Colorectal Cancer Therapy Using a Pediococcus pentosaceus SL4 Drug Delivery System Secreting Lactic Acid Bacteria-Derived Protein p8

  • An, Byung Chull;Ryu, Yongku;Yoon, Yeo-Sang;Choi, Oksik;Park, Ho Jin;Kim, Tai Yeub;Kim, Song-In;Kim, Bong-Kyu;Chung, Myung Jun
    • Molecules and Cells
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    • v.42 no.11
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    • pp.755-762
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    • 2019
  • Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.

A STUDY ON CLINICAL USE OF HYPERBARIC OXYGEN THERAY OF THE ORAL AND MAXILLOFACIAL REGION (고압산소치료의 구강악안면영역에서의 임상적 이용에 관한 연구)

  • Lyoo, Jung-Ho;Um, Ki-Hun;Bae, Jun-Su;You, Jun-Young;Jang, Myung-Jin;Kim, Yong Kwan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.5
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    • pp.447-452
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    • 2001
  • Hyperbaric oxygen therapy(HBO) is defined as breathing 100% oxygen while in an enclosed system pressurized to greater than on atmosphere(sea level). This increased oxygen delivery furthers your body's ability to kill germs and to increase healing. HBO is a supplemental therapy to be used in addition to the current medical and surgical therapy you are receiving. HBO typically is used to complement treatments of medical problems such as bone infections, complication of radiotherapy, and certain chronic, non-healing wounds. On an emergency basis, the chamber also is used to treat problems such as carbon monoxide poisoning and the decompression sickness. We analysed stastically cases which are treated by hyperbaric oxygen therapy in point of oral and maxillofacial region on the Kangnam General Hospital for aid in comprehension and application of this therapy. Total 760 patients were treated at Gangnam General Hospital from July 1996 to September 1999. They were classified by region to Decompression sickness(DCS), Carbon monoxide poisoning(CO), General surgery(GS), Orthopedics(OS), Oral and Maxillofacial surgery(OMFS), others. Patients of Oral and Maxillofacial surgery were divided by diseses to Osteomyelitis, Osteoradionecrosis, Reconstruction, Bone graft, Difficult wounds, others. The results were as follows. 1. This institute conducts HBO therapy for DCS which takes up 62% and 10.5% for OMF region. 2. In OMF region, Osteomyelitis is 40%, Osteoradionecrosis is next, Bone graft, and Reconstruction is a row. 3. According to our precious study, HBO has been frequently conducted in OMF region compared to past, however, it is less actively conducted in this area for research than other conturies. Therefore, We need further application to the clinical use.

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The Evolution and Value of Diphtheria Vaccine (디프테리아 백신의 진화와 물리화학적, 분자생물학적, 면역학적 지식의 진보에 따른 새로운 백신의 개발에 관한 고찰연구)

  • Bae, Kyung-Dong
    • KSBB Journal
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    • v.26 no.6
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    • pp.491-504
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    • 2011
  • This review article provides an overview of the evolution of diphtheria vaccine, its value and its future. Diphtheria is an infectious illness caused by diphtheria toxin produced by pathogenic strains of Corynebacterium diphtheriae. It is characterized by a sore throat with membrane formation due to local tissue necrosis, which can lead to fatal airway obstruction; neural and cardiac damage are other common complications. Diphtheria vaccine was first brought to market in the 1920s, following the discovery that diphtheria toxin can be detoxified using formalin. However, conventional formalin-inactivated toxoid vaccines have some fundamental limitations. Innovative technologies and approaches with the potential to overcome these limitations are discussed in this paper. These include genetic inactivation of diphtheria toxoid, innovative vaccine delivery systems, new adjuvants (both TLR-independent and TLR-dependent adjuvants), and heat- and freeze-stable agents, as well as novel platforms for producing improved conventional vaccine, DNA vaccine, transcutaneous (microneedle-mediated) vaccine, oral vaccine and edible vaccine expressed in transgenic plants. These innovations target improvements in vaccine quality (efficacy, safety, stability and consistency), ease of use and/or thermal stability. Their successful development and use should help to increase global diphtheria vaccine coverage.

SURFACE CHANCE OF EXTERNAL HEXAGON OF IMPLANT FIXTURE AND INTERNAL HEXAGON OF ABUTMENT AFTER REPEATED DELIVERY AND REMOVAL OF ABUTMENT (지대주의 반복적인 착탈에 따른 임플랜트 고정체의 external hexagon과 지대주 internal hexagon의 변화에 관한 연구)

  • Jung Seok-Won;Kim Hee-Jung;Chung Chae-Heon
    • The Journal of Korean Academy of Prosthodontics
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    • v.43 no.4
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    • pp.528-543
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    • 2005
  • Statement of problem: Repeated delivery and removal of abutment cause some changes such as wear, scratch or defect of hexagonal structure. It may increase the value of rotational freedom(RF) between hexagonal structures. Purpose: The purpose of this study was to evaluate surface changes and rotational freedom between the external hexagon of the implant fixture and internal hexagon of abutment after repeated delivery and removal under SEM and toolmaker's microscope. Materials and methods: Implant systems used for this study were 3i and Avana. Seven pail's of implant fixture, abutment and abutment screws for each system were selected and all fixtures were perpendicularly mounted in liquid unsaturated polyesther with dental surveyor. Each one was embedded beneath the platform of fixture. Surfaces of hexagonal structure before repeated closing and opening of abutment were observed using SEM and rotational freedom was measured by using toolmaker's microscope. Each abutment was secured to the implant future by each abutment screw with recommended torque value using a digital torque controller and was repeatedly delivered and removed by 20 times respectively. After experiment, evaluation for the change of hexagonal structures and measurement of rotational freedom were performed. Result : The results were as follows; 1. Wear of contact area between implant fixture and abutment was considerable in both 3i and Avana system. Scratches and defects were frequently observed at the line-angle of hexagonal structures of implant fixture and abutment. 2. In the SEM view of the external hexagon of implant fixture, the point-angle areas at the corner edge of hexagon were severely worn out in both systems. It was more notable in the case of 3i systems than in that of Avana systems. 3. In the SEM view of the internal hexagon of abutment, Gingi-Hue abutment of 3i systems showed severe wear in micro-stop contacts that were machined into the corners to prevent rotation and cemented abutment of Avana systems showed wear in both surface area adjacent to the corner mating with external hexagon of implant fixture. 4 The mean values of rotational freedom between the external hexagon of the implant fixture and internal hexagon of abutment were 0.48$\pm$0.04$^{\circ}$ in pre-tested 3i systems and 1.18$\pm$0.25$^{\circ}$ after test, and 1.80$\pm$0.04$^{\circ}$ in pre-tested Avana systems and 2.61$\pm$0.16$^{\circ}$ after test. 5. Changes of rotational freedom after test shouted statistical)y a significant increase in both 3i and Avana systems(P<0.05, paired t-test). 6. Statistically, there was no significant difference between amount of increase in the rotational freedom of 3i systems and amount of increase in that of Avana ones(P>0.05, unpaired t-test). Conclusion: Conclusively, it was considered that repeated delivery and remove of abutment by 20 times would not have influence on screw joint stability. However, it caused statistically the significant change of rotational freedom in tested systems. Therefore, it is suggested that repeated delivery and remove of abutment should be minimal as possible as it could be and be done carefully Additionally, it is suggested that the means or treatment to prevent the wear of mating components should be devised.