• 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 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.

• Korean Journal of Clinical Pharmacy
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• v.10 no.1
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• pp.1-6
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• 2000

백내장 수술 추 염증치료를 위해 일반적으로 부작용이 많은 국소 점안 스테로이드를 사용해왔다. 최근 NSAID계열의 점안액이 항염증 치료약물로 개발되면서 선택적인 약물치료가 가능하게 되었으나 단일치료약물로 사용하는 경우는 드물다. 본 연구는 NSAID계 diclofenac 점안액의 백내장 수술 후 염증치료 효과를 스테로이드체 dexamethasone 점안액과 비교하여 단일 치료약물로서 사용할 수 있는 지 연구하고자하였다. 백내장 수술을 받은 환자로서 안압이 22 mmHg 이상 당뇨환자, 수술대상 눈에 이미 질환 및 수술 경력이 있는 자를 제외하였다. 백내장 수술 후 항염종 약물로서 diclofenac 또는 dexamethasone을 28일 동안 투여하고 항염증효과의 평가를 위하여 세극등 검사로저 전방내 염증세포와 결막, 각막등의 전안부 관찰을 수술 전, 수술 후 1, 3, 7, 14, 28일에 시행하였고, 시력검사는 수술 추 7, 28일에 시행하였다. 안전성의 평가는 안압검사와 세극등 검사상 관찰된 이상소견으로 평가하였다. 총 73명의 연구대상 중 dexameasone군은 41명, diclofenac군은 32명이며 두 군간에 나이, 백내장의 심한 정도, 안구질환 등에 있어 유의한 차이가 없었다 전방내 항염증세포수의 감소에서 두 군간에 유의할 만한 차이가 없었고, 수술 후 최대 교정 시력에서도 동일한 효과를 보였다. 안전성에서 안압의 상승이 두군간에 통계적인 유의한 차이를 보이지 않았으나 dexamethasone군에서 1명의 환자가 45 mmHg 이상 증가하여 약물치료가 필요하였으나 diclofenac군에서는 안압이 상승한 환자가 없었다. 결론적으로 효능 및 안전성에서 두 약물간에 통제적, 임상적으로 유의한 차이가 없었으며 diclofenac 점안액은 백내장 수술 후 항염증치료제로서 충분한 효과가 있으며 안압상승, 감염 등 부작용이 우려되는 dexamethasone점안액의 대체약물로 사용될 수 있을 것으로 평가된다.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.437-442
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• 2009

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than $3\;{\mu}M$, diclofenac inhibited reversibly the $Na^+$ current and did irreversibly the L-type $Ca^{2+}$ channels-mediated inward current $(IC_{50}=12.89\pm0.43\;{\mu}M)$ in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type $Ca^{2+}$ currents but not the $Na^+$ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type $Ca^{2+}$ channel, leading to the impairment of E-C coupling in cardiac myocytes.

• Archives of Pharmacal Research
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• v.16 no.1
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• pp.71-74
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• 1993

The protective effect of adenosine triphosphate (ATP) on gastic ulcer induced in rats has been studied. Gastic ulceration was induced by hypothemic restraint stress or dicolofenac sodium. Gastic acid secretion and mucosal injury produced by the hypothemic restraint stress was greater as compared with those produced by diclofenac sodifum. ATP significantly reduced area of injury, however, increased cyclic adenosine monophosphate (cATP) content. Administration of dipyridamole along with ATP did not change the total lesion area in both models when compared to ATP alone. Aminophyline antagonized antagonized the protective effect of ATP on the injured area. Famotidine was found to be effective in reducing gastric acid output as well as the total injured area without any change in cAMP content when given along with ATP.

• 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.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.351-356
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• 2004

A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol: ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.

• Advances in Traditional Medicine
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• v.8 no.3
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• pp.243-251
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• 2008

The effect of alcoholic extracts of Costus specious (Family: Zingiberaceae) was evaluated in experimental models of pain and inflammation. Oral administration of 100, 200 and 300 mg/kg of C. specious extracts were used for the above study. Crude extracts of C. specious (300 mg/kg dose) showed maximum time needed for the response against thermal stimuli ($7.242\;{\pm}\;0.532\;s$) which is comparable to diclofenac sodium ($8.471\;{\pm}\;0.25\;s$) in the hot plate test. The MPH (Maximum Possible Analgesia) has been found to be 14.285 for 300 mg/kg dose of the crude extract while the MPH for diclofenac was 15.857 after 60 min of administration in the hot tail-flick method. The crude extract at 300 and 200 mg/kg doses showed significant reduction in acetic acid induced writhings in mice with a maximum effect of 59.661% reduction at 300 mg/kg dose which is comparable to standard diclofenac sodium (73.4%). Alcoholic extract of C. specious showed significant inhibition in serotonin and egg albumin induced hind paw oedema in rats at 100, 200 and 300 mg/kg of the crude extracts respectively (Serotonin induced edema 44.22; 53.75; 58.51%; egg albumin induced edema - 41.317; 53.892; 59.880% inhibition after 4 h respectively). The antiinflammatory effects showed by the extract were comparable to that of standard indomethacin 5 mg/kg (Serotonin induced edema 77.56%; egg albumin induced edema 77.844% inhibition after 4 h). These results suggest that the extract possesses both the anti-inflammatory and analgesic activity on mice and rat model.

• Advances in Traditional Medicine
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• v.9 no.4
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• pp.326-334
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• 2009

The effect of alcoholic extract of Anthocephalus (A.) Cadamba Roxb. was evaluated in experimental models of pain and ulcer. Hot tail flick test, hot plate test and acetic acid induced writhing test were employed for evaluating the peripheral as well as central analgesic mechanism exerted by the extracts. Gastroprotective activity was examined by HCl and ethanol induced gastric damage test. Test group received crude extract 500 mg/kg showed maximum time needed for the response against thermal stimuli (6.26 ${\pm}$ 0.439 s) which is comparable to diclofenac sodium (6.56 ${\pm}$ 0.381 s) in hot tail flick method. These experimental results also followed the experimental results of hot plate test where crude extract 500 mg/kg showed maximum time needed for the response against thermal stimuli (4.74 ${\pm}$ 0.234 s) which is comparable to diclofenac sodium (5.58 ${\pm}$ 0.585 s). The crude extract at 500 and 250 mg/kg showed significant reduction in acetic acid induced writhing in mice with a maximum effect of 68.026% reduction at 500 mg/kg dose which is comparable to standard diclofenac sodium (79.93%). In gastroprotective study the extract of A. Cadamba (250 and 500 mg/kg) significantly inhibited ulceration induced by both HCl and ethanol dose dependently. Results of the study suggest that the extract possesses both analgesic and gastroprotective activity on mice.