• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.417-422
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• 2005

This study was aimed to design and formulate the moisture-activated patches containing ofloxacin and lidocaine for antibacterial and local anesthetic action. The solubility of lidocaine at $32^{\circ}C$ in various vehicles decreased in the rank order of PG $759.5{\pm}44.5\;mg/mL$ > PGL > IPM > PEG 300 > PEG 400 > Ethanol > PGMC > DGME > PGML > OA > $Captex^{\circledR}\;300$ > $Captex^{\circledR}\;200$ > water $(4.0{\pm}0.1\;mg/mL)$. Ofloxacin revealed very low solubility, which the highest solubility was obtained from PEG 400 $(18.7{\pm}6.3\;mg/mL)$ among the vehicles used. The addition of lactic acid increased the solubility of ofloxacin dramatically; the solubility at 5% lactic acid was $133.7{\pm}9.7\;mg/mL$. As $2-hydroxypropyl-{\beta}-cyclodextrin$ was added at the concentrations of 40, 80, 120, 160 and 200 mM, the solubilities of lidocaine and ofloxacin were enhanced up to three and two times, respectively, with concentration-dependent pattern. Gel intermediates for filmtype patches were prepared with mucoadhesive polymer, viscosity builders, lidocaine or ofloxacin at pH values from 5 to 7. Gels were cast onto a release liner and dried at room temperature. Dried patch was attached onto an adhesive backing layer, thus forming a patch system. Patches containing a single drug component were characterized by in vitro measurement of drug release rates through a cellulose barrier membrane. The release study was carried out at $37^{\circ}C$ using a Franz-type cell. Receptor solutions were isotonic phosphate buffers (pH 7.4). Samples $(100\;{\mu}L)$ were taken over 24 hours and quantitated by a verified HPLC method. The releases from all tested were proportional to the square root of time. The release rates were 0.9, 157.3 and $281.7\;{\mu}g/cm^{2}/min^{1/2}$ for the lidocaine patches and 19.8,37.2 and $50.7\;{\mu}g/cm^{2}/min^{1/2}$ for the ofloxacin patches at the concentrations of 0.3, 0.5 and 1 %, respectively. The release rates were dose dependent in both drug patches $(R^{2}\;=\;0.9077\;for\;lidocaine;\;R^{2}\;=\;0.9949\;for\;ofloxacin)$ and those were also thickness-dependent $(R^{2}\;=\;0.9246\;for\;lidocaine;\;R^{2}\;=\;0.9512\;for\;ofloxacin)$.

• Bulletin of the Korean Chemical Society
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• v.30 no.9
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• pp.1985-1988
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• 2009

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loading paclitaxel have been deposited on coronary stents by self-assembling properties of colloidal particles. The layers of the nanoparticles were enhanced to a sufficient mechanical strength by a thermal process under the proper temperature and humidity conditions. In vitro release studies proved the controlled paclitaxel release of the nanoparticle layers. This technique gives rise to a new range of applications for nanoparticles and drug-eluting stents.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.1939-1943
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• 2014

Solid dispersion (SD) system of everolimus (EVR) with Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) was prepared using melt granulation technique with the aim of improving the physicochemical properties and dissolution rate. The solid state characterization using scanning electron microscopy and X-ray powder diffraction, indicated that the drug was homogeneously distributed in the surfactant carrier in a stable amorphous form. The dissolution rate of EVR from the optimized SD composed of the drug, Gelucire 50/13 and microcrystalline cellulose in a weight ratio of 1:5:10, was markedly rapid and higher than that from the drug powder and the market product (Afinitor$^{(R)}$, Novartis Pharmaceuticals) in all dissolution mediums tested from pH 3.0 to pH 6.8. The results of this study suggest that formulation of SD with Gelucire 50/13 using melt granulation procedure may be a simple and promising approach for improving the dissolution rate and oral absorption of the anti-cancer agent without the need for using an organic solvent.

• Advances in nano research
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• v.13 no.1
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• pp.87-96
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• 2022

Drug self-delivery systems can easily realize combination drug therapy and avoid carrier-induced toxicity and immunogenicity because they do not need non-therapeutic carrier materials. So, designing appropriate drug self-delivery systems for specific diseases can settle most of the problems existing in traditional drug delivery systems. Retinal pigment epithelium is very important for the homeostasis of retina. However, it is vulnerable to oxidative damage and difficult to repair. Worse still, the antioxidants can hardly reach the retina by non-invasive administration routes due to the ocular barriers. Herein, the targeted group (folic acid) and antioxidant (melatonin) have been grafted on the surface of ZnO quantum dots to fabricate a new kind of drug self-delivery systems as a protectant via eyedrops. In this study, the negative nanoparticles with size ranging in 4~6 nm were successfully synthesized. They could easily and precisely deliver drugs to retinal pigment epithelium via eyedrops. And they realized acid degradation to controlled release of melatonin and zinc in retinal pigment epithelium cells. Consequently, the structure of retinal pigment epithelium cells were stabilized according to the expression of ZO-1 and β-catenin. Moreover, the antioxidant capacity of retinal pigment epithelium were enhanced both in health mice and photic injury mice. Therefore, such new drug self-delivery systems have great potential both in prevention and treatment of oxidative damage induced retinal diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1149-1154
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• 2006

Repeated administration of all addictive drugs, including nicotine, can produce sensitization of extracellular dopamine levels in the nucleus accumbens and behavioral sensitization in rat, as evidenced by an enhanced locomotor response and increased dopamine release in brain to a subsequent injection of the drug. In order to investigate the effect of Zizyphus jujuba extract on repeated nicotin-induced sensitization, rats were given repeated injection of saline or nicotine (0.4 mg/kg s.c., twice a day for 7 d), followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine (0.4 mg/kg s.c.) and a direct local challenge of 3 mM a larger increase in locomotor activity and extracellular dopamine release in the nucleus accumbens in nicotine-pretreated rats than in saline-pretreated rats, respectively. Zizyphus jujuba extract significantly decreases locomotor activitiy and dopamine release in the nucleus accumbens induced by a nicotine challenge. These results suggest that Zizyphus jujuba extract may attenuate nicotine-induced neurochemical and behavioral sensitization and may be effective in suppressing compulsive nicotine-seeking behavior.

• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1096-1101
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• 2003

To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: $V_d$=0.04336L/kg, $T_{1/2} \beta$=1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.

• YAKHAK HOEJI
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• v.39 no.5
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• pp.487-494
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• 1995

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 60 mol, 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 40.mu.m. 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.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.43-51
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• 1995

The in vitro skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0,95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin, P-800) (40/60) lipophilic binary vehicle and an ethanol/water (60/40) hydrophilic binary vehicle with lauric acid, The skin permeability of the drugs was enhanced by the use of the ethanol/P-800 (40/60) binary vehicle or the ethanol/water (60/40) binary vehicle with lauric acid; permeation rate was increased and lag time' was decreased. The relationship between lipophilicity and skin permeation rate of the drugs showed parabolic shapes with their peaks at much greater hydrophilic range compared with other past references. In the in vivo skin absorption of theophylline using abdominal rat skin, the ethanol/P-800 (40/60)-7% (w/w) ethycellulose gel produced a good feature as a sustained-release preparation, and the ethanol/water (60/40)-3 % (w/w) HPMC gel with lauric acid showed the highest BA value. The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/P-800 (40/60) binary vehicle and ethanol/water (60/40) binary vehicle with lauric acid would be good candidates for clinical transdermal application of hydrophilic drugs.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.224-230
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• 1995

Recently, many attempts have been made to use hydrogels of various polymers as delivery systems of various drugs and bioactive materials to prolong and control their phamacological activities. In this study, we have evaluated the physico-chemical properties of methacrylic acid-methyacrylic acid methyl ester copolymer 9Eudispert mv)m a acrylic resin hydorgel, and its application to transdermal delivery system. In the dissolution tests, the release rate of salicylic acid (SA) and sodium salicylate (SOd. SA) were faster than lidocain (LD) and lidocain-HCl(LD-HCl). As the concentration of Eudispert mv polymer increased, the extensibility of Eudispert mu hydrogel decreased, whereas the swelling ratio increased. The more NaOH and polymer concentration increased, the more osmotic pressure linearly increased. The skin permeation of Sod. SA, an acidic model drug, was remarkably enhanced by Eudispert mv hydrogel. All fatty acids, except for Sod. glycolate, dramatically increased the skin permeation flux in Eudispert mu hydrogel containing LD-Hcl, a basic model drug. Consequently, it is suggested that Eudispert mv hydrogel may be used as potential transdermal delivery vehicle.