• Journal of the Korean Society of Visualization
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• v.10 no.2
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• pp.32-38
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• 2012

In recent years a unique drug delivery system named as the transdermal drug delivery system has been developed which can deliver drug particles to the human skin without using any external needle. The solid drug particles are accelerated by means of high speed gas flow through a shock tube imparting enough momentum so that particles can penetrate through the outer layer of the skin. Different systems have been tried and tested in order to make it more convenient for clinical use. One of them is the contoured shock tube system (CST). The contoured shock tube consists of a classical shock tube connected with a correctly expanded supersonic nozzle. A set of bursting membrane are placed upstream of the nozzle section which retains the drug particle as well as initiates the gas flow (act as a diaphragm in a shock tube). The key feature of the CST system is it can deliver particles with a controllable velocity and spatial distribution. The flow dynamics of the contoured shock tube is analyzed numerically using computational fluid dynamics (CFD). To validate the numerical approach pressure histories in different sections on the CST are compared with the experimental results. The key features of the flow field have been studied and analyzed in details. To investigate the performance of the CST system flow behavior through the shock tube under different operating conditions are also observed.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.321-329
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• 2006

Albuterol, a selective ${\beta}_2$-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.

• 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.

• Proceedings of the KSME Conference
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• 2001.11b
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• pp.622-627
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• 2001

Microjet flows are often encountered in many industrial applications of micro-electro-mechanical systems as well as in medical engineering fields such as a transdermal drug delivery system for needle-free injection of drugs into the skin. The Reynolds numbers of such microjets are usually several orders of magnitude below those of larger-scale jets. The supersonic microjet physics with these low Reynolds numbers are not yet understood to date. Computational modeling and simulation can provide an effective predictive capability for the major features of the supersonic microjets. In the present study, computations using the axisymmetic, compressible, Navier-Stokes equations are applied to understand the supersonic microjet flow physics. The pressure ratio of the microjets is changed to obtain both the under- and over-expanded flows at the exit of the micronozzle. Sonic and supersonic microjets are simulated and compared with some experimental results available. Based on computational results, two microjets are discussed in terms of total pressure, jet decay and supersonic core length.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.158-163
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• 2012

Lidocaine has been studied for many chronic pain conditions, including postherpetic neuralgia (PHN) and recently it has also been increasingly used in transdermal drug delivery systems. In this study, pharmacokinetics of a lidocaine patch was studied in four hairless male rats. The plasma concentration was determined by a validated LC/MS/MS method after applying a $3{\times}2cm^2$ (30mg) patch for 12 hours. From the plasma lidocaine concentration vs time curves, $AUC_{0-20h}$, Cmax, and Tmax of lidocaine patch were $2,926.32{\pm}335.28ng{\cdot}h/ml$, $256.86{\pm}29.63ng/ml$, and $6.00{\pm}2.31h$, respectively.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.298-306
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of vehicle composition and drug loading dose on the skin permeation property were investigated. And in vivo skin absorption property studied by analysing the $C_{max}$ and AUC was investigated after applying the developed plaster systems on rabbit back skin. Addition of isopropyl myristate (IPM) and IPM-diethylene glycol monoethyl ether (DGME) cosolvent in the plaster showed higher permeation rates than those from propylene glycol laurate-DGME cosolvent systems. As the concentration of LP in the plaster increased from 0.56 mg/$\textrm{cm}^2$ to 1.19 mg/$\textrm{cm}^2$, the drug release and skin permeation rates increased linearly. At loading dose of 1.19 mg/$\textrm{cm}^2$, the flux reached 35.6 $\mu$g/$\textrm{cm}^2$/hr. New LP plasters showed a good adhesive property onto skin, and showed no crystal formation. The AU $C_{0-24hr}$ and $C_{max}$ after dermal application of LP plaster (60 mg/70 $\textrm{cm}^2$) were found to be 6951$\pm$230 ng.hr/ml and 400$\pm$44 ng/ml, respectively. And the plasma concentration maintained above 300 ng/ml up to 24 hr period. In the carrageenan-induced rat paw edema test, LP plaster showed similar inhibition rate with marketed ketoprofen (Ketoto $p^{R}$) plaster.aster.r.

• Proceedings of the Korean Vacuum Society Conference
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• 2014.02a
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• pp.411.1-411.1
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• 2014

This study evaluates the utility of an antibacterial microneedle composed of green tea extract (GT) and hyaluronic acid (HA), for the efficient delivery of GT. These microneedles have the potential to be a patient-friendly method for the conventional sustained release of drugs. In this study, a fabrication method using a mold-based technique to produce GT/HA microneedles with a maximum area of ${\sim}60mm^2$ with antibacterial properties was used to manufacture transdermal drug delivery systems. Fourier transform infrared (FTIR) spectrometry was carried out to observe the potential modifications in the microneedles, when incorporated with GT. The degradation rate of GT in GT/HA microneedles was controlled simply by adjusting the HA composition. The effects of different ratios of GT in the HA microneedles were determined by measuring the release properties. In HA microneedles loaded with 70% GT (GT70), a continuous higher release rate were sustained for 72 h. The in vitro cytotoxicity assays demonstrated that GT/HA microneedles are not generally cytotoxic to chinese hamster ovary cells (CHO-K1), human embryonic kidney cells (293T), and mouse muscle cells (C2C12), which were treated for 12 and 24 h. Antimicrobial activity of the GT/HA microneedles was demonstrated by ~95% growth reduction of gram negative [Escherichia coli (E. coli), Pseudomonas putida (P. putida) and Salmonella typhimurium (S. typhimurium)] and gram positive bacteria [Staphylococcus aureus (S. Aureus) and Bacillus subtilis (B. subtilis)], with GT70. Furthermore, GT/HA microneedles reduced bacterial growth in the infected skin wound sites and improved skin wound healing process in rat model.

• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.29-36
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• 2003

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of clenbuterol was investigated in hairless mouse skin after application of 50/50 buffer(pH 10)/propylene glycol solvent mixture. The enhancing effects of various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, fatty acids and some other enhancers on the permeation of clenbuterol were evaluated using Franz diffusion cell. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of clenbuterol approximately 39.33-fold compared with the control without penetration enhancer, followed by menthone with enhancement ratio of 23.57. Nonionic surfactants did not have significant enhancing effects. N-Lauryl-2-pyrrolidone increased the permeability of clenbuterol approximately 4.51-fold compared with the control. Lauric acid increased the permeability of clenbuterol approximately 35.57-fold with decreasing the lag time from 2.64 to 0.52 hr. Oleic acid, linoleic acid, linolenic acid and capric acid showed enhancement ratio of 22.62, 19.60, 17.45 and 16.51, respectively. $Labrafil^{\circledR}$ enhanced the permeability of clenbuterol 9.24-fold compared with that without enhancer.