• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.11-14
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• 1997

This laboratory has recently reported the solubility and in vivo absorption enhancement of diclofenac sodium by ${\beta}-cyclodextrin$ complexation. The acute gastroduodenal mucosa injury provoked by administration of 34 mg/kg and 68 mg/kg of a diclofenac sodium (DS) and equivalent dose of new formulation [diclofenac sodium-beta-cyclodextrin complexation$(DS-{\beta}-CD)$] was evaluated and compared. Microscopic examinations, performed after 18-hrs treatment, demonstrated that $DS-{\beta}-CD$ was less gastrolesive than DS. The drop in gastrophy after a single dose of the assigned drug was considerably greater for DS than for $DS-{\beta}-CD$, which registered similar values to control. Since gastrophy is an expression of the anatomy-functional integrity of the gastric barrier, the results indicate that $DS-{\beta}-CD$ exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term, $DS-{\beta}-CD$ appears to be less gastrolesive than the standard DS formulation.

• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.2
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• pp.101-104
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• 2011

Nicolau syndrome is a rare adverse reaction at the site of an intramuscular injection, and is characterized by severe pain immediately after the injection and rapid development of distinct skin lesions. As this syndrome is rare, it may be overlooked at the early clinical phase and subsequently, clinical outcomes may be worse due to delay in treatment. We report on a female who developed Nicolau syndrome following intramuscular diclofenac injection, which required surgical reconstruction. Understanding the characteristics of Nicolau syndrome and careful surveillance for relevant clinical features may help physicians to more quickly diagnose and treat this condition.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.95-100
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• 2001

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room temperature. 1-Octanol/water partition coefficients (Log P) and capacity factors (k') were measured to determine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.91-94
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• 2004

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution ad dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based sold suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Ver small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about $32^{\circ}C$ was a sold for at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue colo of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/ P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in thε rectum for at least 4 h. Our results indicated that the poloxamer-based sold suppository with P 124 and P 188 would be a candidate of rectal dosage form for diclofenac sodium.

• Journal of Veterinary Clinics
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• v.27 no.4
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• pp.315-324
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• 2010

The effect of beta-glucan ($Polycan^{TM}$) derived from Aureobasidium pullulans SM-2001 were observed on, collagen-induced rheumatoid arthritis (RA) in DBA mice. Six week-old male DBA/1J mice were immunized by the intradermal injection of $200\;{\mu}g$ of bovine type II collagen with the equal volume of complete Freund's adjuvant at the tail base on day 1. On day 21, the mice were boosted by the intradermal injection of $200\;{\mu}g$ of bovine type II collagen with incomplete Freund's adjuvant. From the first immunization, mice had been administered $Polycan^{TM}$ (21.25, 42.5 and 85 mg/kg), diclofenac and vehicle once a day for 4 weeks, respectively. Collagen-induced hyperimmunities and arthritis signs were markedly and dose-dependently inhibited by treatment of $Polycan^{TM}$ compared with RA control except for tibial cartilages of $Polycan^{TM}$ 21.25 group. $Polycan^{TM}$ effectively inhibited the histopathological changes of collagen-induced arthritis and hyper-immunities.

• Journal of Korean Society of Environmental Engineers
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• v.31 no.10
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• pp.831-838
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• 2009

In order to evaluate a removal characteristic of diclofenac, ibuprofen and naproxen by oxidizing agents, $Cl_2,\;O_3$ and $O_3/H_2O_2$ are used as oxidants in this study. In case of that $Cl_2$ is used for oxidizing pharmaceuticals, ibuprofen is not removed entirely at $Cl_2$ dose range of 0.5~5.0 mg/L for 60 minutes, however, removal tendency of diclofenac and naproxen are so obviously at $Cl_2$ dose higher than 0.5 mg/L. In addition, as $Cl_2$ dose and contact time are increased, the removal rate of diclofenac and naproxen is enhanced. When $O_3$ is used as oxidizing agent, ibuprofen is not eliminated at $O_3$ dose range of 0.2~5.0 mg/L. On the contrary, 72~100% of diclofenac and 49~100% of naproxen are removed at $O_3$ dose of 0.2~5.0 mg/L. From experiments using $O_3/H_2O_2$ as an oxidant, we can find that $O_3/H_2O_2$ is much more effective than $O_3$ only for removal of diclofenac and naproxen. Moreover, the efficiency is raised according to increase of $H_2O_2$ dose, however, experiments using $O_3/H_2O_2$ show that oxidation of pharmaceuticals is less effective as $H_2O_2$ to $O_3$ ratio increased to above approximately 1.0. On reaction rate constant and half-life of diclofenac, ibuprofen and naproxen depending on $Cl_2$, $O_3$ and $O_3/H_2O_2$ dose, an oxidation of pharmaceuticals by $Cl_2$ and $O_3$ particularly has a comparatively high reaction rate constant and short half-life comparing $O_3/H_2O_2$. From above results, we can fine that diclofenac and naproxen can be easily eliminated in oxidation processes.

• Analytical Science and Technology
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• v.21 no.3
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• pp.191-200
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• 2008

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants in aquatic environmental samples. Therefore, it required rapidly and certainly analytical method for pharmaceuticals which are existed in environment. In this study, Liquid chromatography/tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI) was used to measure the concentrations of 7 pharmaceuticals (quinoxaline-2-carboxylic acid, acetylsalicylic acid, diclofenac-Na, naproxen, ibuprofen, mefenamic acid, talniflumate) from environmental water or aquatic samples simultaneously. Effective sample clean-up by solid-phase extraction (SPE) prior to LC-MS/MS analysis is necessary. For further purification, Mixed Cation eXchange (MCX) and Hydrophilic-Lipophilic Balance (HLB) solid-phase extraction (SPE) cartridges were used to eliminate the remaining interferences. LODs (Limits of Detection) and MDLs (Method Detection Limits) for the spiked sample in fresh water were in the range of 0.05~1.50 pg/mL and 0.17~4.90 pg/mL, respectively. The absolute recovery in the concentration of 1.0 ng/mL were between 81.9 and 116.3%. The acidic pharmaceuticals were detected in concentrations of 0.018~16.925 ng/mL in aquatic environmental samples.