• Journal of Pharmaceutical Investigation
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• 제26권3호
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• pp.169-174
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• 1996

Inclusion complexes of diclofenac sodium with ${\beta}-cyclodextrin$ were prepared in aqueous solution, alkaline solution and solid phase. The interaction of diclofenac sodium with ${\beta}-cyclodextrin$ in pH 9.0 alkaline solution was evaluated by the solubility method and the instrumental analysis such as thermal analysis, infrared spectroscopy, X-ray diffractometry. The solubility of diclofenac sodium was increased linearly with the increase in the concentration of ${\beta}-cyclodextrin$up to 0.15 mol and showed that the aqueous solubility rate of diclofenac sodium was significantly increased by complex with ${\beta}-cyclodextrin$. The optimum composition of this complex was one molecule of ${\beta}-cyclodextrin$ included 1.59 molecular weight of diclofenac sodium as a guest molecule. The pharmacokinetic parameters of the diclofenac sodium and the complex with ${\beta}-cyclodextrin$ were studied in rats by oral route. $T_{max}$ between drug alone and inclusion complex showed significant difference to be 120 minute and 20 minute respectively. Both of $C_{max}$ and AUC of inclusion complex was about 40% higher than drug alone. It is estimated from the data in this study that complexation of diclofenac sodium with ${\beta}-cyclodextrin$ increased the absorption rate and improved the bioavalability of the diclofenac sodium by the formation of a water-soluble complexes.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.162-167
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• 2003

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers. since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0％ of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

• Journal of Dental Anesthesia and Pain Medicine
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• 제20권1호
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• pp.19-27
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• 2020

Background: Surgical extraction of third molars is associated with postoperative pain and swelling at the extraction site. Pain is commonly managed using non-steroidal anti-inflammatory drugs (NSAIDs). Postoperative pain is usually moderate to severe in the first 12 h postoperatively and lasts for 3-5 days. However, with NSAIDs, these symptoms usually subside within 24 h. Diclofenac sodium and etodolac are NSAIDs, more selectively cyclooxygenase-2 inhibitors, with good analgesic efficacies. Methods: We compared the safety and analgesic efficacy of diclofenac sodium with etodolac peroral after surgical extraction of third molars in a double-blind, double-dummy, parallel-group study. The subjective pain improvement and pain relief after 2, 6, 24, 48, and 72 h using the visual analogue scale were measured as the study outcome. Results: Etodolac was equivalent to diclofenac sodium in pain alleviation at all postoperative time periods. No significant differences were found between diclofenac sodium and etodolac groups (P > 0.05). Both study medications were well tolerated and safe with mild adverse effects in only a few participants. Conclusion: Diclofenac sodium and etodolac are comparable in terms of analgesic efficacy and safety after surgical removal of third molars.

• Journal of Pharmaceutical Investigation
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• 제34권2호
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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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• 제27권1호
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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.

• Archives of Pharmacal Research
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• 제16권1호
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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.

• 약학회지
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• 제52권4호
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• pp.293-298
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• 2008

Non-steroidal anti-inflammatory drug (NSAID)-induced gut damage and bacterial translocation (BT) have not been studies well, especially from the perspective of time after administration of NSAIDs. We therefore examined these changes in animals. The study was performed on 5 groups of rat; a control group (group A) and diclofenac groups (groups B, C, E, and F). Rats in the diclofenac groups were orally administered diclofenac sodium before intestinal permeability (IP) measurement (group B, 1 h before measurement; group C, 10 h before; group D, 22 h before; and group E, 52 h before). The IP, stool pellet number, serum biochemical profile, enteric bacterial number, and BT in the mesenteric lymph nodes (MLNs), liver, spleen, kidney and heart were measured. The administration of diclofenac resulted in significantly increased IP, caused intestinal protein loss, decreased stool pellet number, caused enteric bacterial overgrowth and increased BT in multiple organs in groups A, B, C, and D. IF, intestinal protein loss, and the BT in the liver and the spleen in group E were decreased than those in group D. There were no differences in the other parameters between group D and E. In the recovery phase of the diclofenac-induced gut damage, enteric bacterial overgrowth and BT in the kidneys and the heart did not change while the BT in the reticuloendothelial systems such as in the MLNs and liver was decreased.

• Advances in Traditional Medicine
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• 제8권3호
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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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• 제9권4호
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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.

• Journal of Pharmaceutical Investigation
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• 제41권4호
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• pp.211-215
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• 2011

The aim of this study was to develop a stable enteric coated diclofenac sodium (DFS) tablets using Aqua-Polish E without using a subcoat. DFS uncoated tablets were manufactured through the non direct compression process. AquaPolish E white aqueous coating dispersion was used as enteric coating material. This film forming polymer is a mixture of selected polymethacrylic/ethylacrylate copolymers. The stability of the obtained enteric coated tablets was evaluated according to ICH guidelines. No signs of disintegration or cracking was observed when they placed in 0.1N HCl solution (pH1.2), but they were completely disintegrated within 10 minutes when they placed in buffered solution at pH6.8. Dissolution test was also conducted by placing tablets in 0.1 N HCl for 2 hours and then 1 hour in phosphate buffer at pH 6.8. Less than 0.9 % of drug was released in the acidic phase and up to 97% in the basic medium. These findings suggest that aqueous enteric coating with AquaPolish E system is an easy and economical approach for preparing stable DFS enteric coat without the use of a subcoating layer.