Administration Of Diclofenac Sodium Research Articles

Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondroitin sulphate.

The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of CS. Formulations prepared were evaluated for the release of DS and CS over a period of 9 hours in pH 6.8 phosphate buffer using United States Pharmacopeia (USP) type II dissolution apparatus. Along with usual physical properties, the dynamics of water uptake and erosion degree of tablet were also investigated. The in vitro drug release study revealed that HPMC K100CR at a concentration of 40% of the dosage form weight was able to control the simultaneous release of both DS and CS for 9 hours. The release of DS matched with the marketed CR tablet of DS with similarity factor (f(2)) above 50. Water uptake and erosion study of tablets indicated that swelling followed by erosion could be the mechanism of drug release. The in vitro release data of CS and DS followed Korsmeyer-Peppas and zero-order kinetics, respectively. In conclusion, the in vitro release profile and the mathematical models indicate that release of CS and DS can be effectively controlled from a single tablet using HPMC matrix system.

Effect of prenatal exposure to diclofenac sodium on Purkinje cell numbers in rat cerebellum: A stereological study

Diclofenac sodium (DS) is commonly used as a non-steroidal anti-inflammatory drug. Although several adverse effects are clearly established, it is still unknown whether prenatal exposure to DS has an effect on the development of the cerebellum. In this study, we investigated the total number of Purkinje cells of the cerebellum in a control group and in a DS-treated group of male rats using a stereological method. The DS in a dose of 1 mg/kg daily was intraperitoneally injected to the drug-treated group of pregnant rats beginning from the 5th day after mating for a period of 15 days during pregnancy. Physiological serum at 1 ml dose was intraperitoneally injected to the control group of pregnant rats at the same period. After delivery, male offspring were obtained and each main group was divided into two subgroups that were 4-week-old (4W-old) and 20-week-old (20W-old). Our results showed that the total number of Purkinje cells in offspring of drug-treated rats was significantly lower than in the offspring of control animals. These results suggest that the Purkinje cells of a developing cerebellum may be affected by administration of DS during the prenatal period.

Reduction of Gastric Ulcerogenicity During Multiple Administration of Diclofenac Sodium by a Novel Solid-in-Oil Suspension

This article reports a significant reduction of gastric ulcerogenicity by complex formation of a nonsteroidal anti-inflammatory drug with surfactants. Diclofenac sodium (DFNa) was suspended in medium chain triglyceride (MCT) by forming a complex with an edible lipophilic surfactant. Two types of suspensions, prepared through a membrane emulsification with different pore sizes, were evaluated according to the degree of gastric damage following multiple oral administration in rats. It was shown that gastric ulcerogenicity of DFNa was reduced by the surfactant–drug complexes, at doses up to 12 mg/kg, whereas severe gastric damage was observed upon oral administration of the aqueous solution at doses of 6 mg/kg. Comparable blood levels of DFNa were observed after administration of solution and suspension formulations.

Real-time visualization and quantitation of canine gastric mucosal blood flow by contrast-enhanced ultrasonography

Objective. Contrast-enhanced ultrasonography has become a method of choice for evaluating gastric blood flow, but intermittent scanning techniques can sometimes distort the results. Low-mechanical index imaging using Definity as the injected contrast material has been advocated for real-time evaluation of microperfusion in other organs. We investigated the reliability of low-mechanical index imaging using Definity in the evaluation of gastric mucosal blood flow. Material and methods. Under general anesthesia, 10 beagle dogs weighing 9–10 kg underwent real-time harmonic imaging under low acoustic power (mechanical index = 0.2) after intravenous contrast injection using Definity (60 mg/kg). Laser Doppler flow measurement was also performed to evaluate gastric mucosal blood flow. After administration of a diclofenac sodium suppository, low-mechanical index imaging and laser Doppler flowmetry were repeated. Results. Real-time visualization of gastric mucosal blood flow was successful in all dogs undergoing low-mechanical index imaging with Definity. Quantitative assessment of gastric mucosal blood flow was successful in eight dogs. After diclofenac sodium administration, gastric mucosal blood flow measured by both laser Doppler flowmetry and contrast ultrasonography decreased in seven of eight dogs; in the other dog, gastric mucosal blood flow increased slightly. A strong positive correlation was evident between blood flow measured by laser Doppler flowmetry and low-mechanical index imaging (r=0.777, p<0.005). Conclusions. Low-mechanical index imaging with Definity is a non-invasive way to evaluate gastric mucosal blood flow in real-time, high-resolutional images, which may have additional important gastrointestinal tract applications.

Decreased Tc-99m MDP Uptake in Myelonecrosis

A 29-year-old man was admitted to the hospital with bone pain and pancytopenia. Multiple bone marrow biopsies and aspirations were performed. Pathologic and morphologic examination of the bone marrow revealed myelonecrosis. Myelonecrosis was diagnosed resulting from excessive administration of diclofenac sodium for renal colic. Large areas of decreased Tc-99m-methylene diphosphonate (MDP) uptake in multiple ribs and eyeglasses-shaped large hypoactive areas in both sacroiliac joints were seen on Tc-99m MDP bone scintigraphy at the third week. It was seen that large areas of decreased Tc-99m MDP uptake in the anterior region of the right second and third ribs and defective small focal areas in the posterior region of the left fourth and fifth ribs persisted, whereas other findings of the ribs and sacroiliac joints improved. Slightly increased activity was seen in the iliac crest biopsy regions on Tc-99m MDP bone scintigraphy at the fourth month.

Effect of Diclofenac on Experimental Pleurodesis Induced by Tetracycline in Rabbits

Background and ObjectivePleurodesis is a frequently preferred procedure in thoracic surgery, and many factors may affect the process. We aimed to determine whether the administration of systemic diclofenac sodium diminishes...

Famotidine prevents canine gastric blood flow reduction by NSAIDs

To investigate the effect of famotidine on gastric blood flow reduction induced by diclofenac sodium, a common non-steroidal anti-inflammatory drug in Japan, using laser Doppler flowmetry in the canine stomach. The gastric mucosal blood flow was measured by laser Doppler flowmetry in 15 healthy male beagles before and 60 min after the administration of diclofenac suppository (1.0 mg/kg) into the rectum. The examination was done in a crossover, single-blinded fashion. All dogs underwent both famotidine (0.5 mg/kg) and placebo (saline) injection simultaneously with the administration of diclofenac. In addition, the tissue concentration of prostaglandin E2 was measured. The blood flow decreased by 18.3 +/- 9.1% in the gastric body, by 26.3 +/- 8.1% in the antrum in the placebo group after the administration of diclofenac sodium, while the decreases seen were significantly smaller in the famotidine group: 3.2 +/- 12.6% in the gastric body and 7.9 +/- 16.5% in the antrum (P = 0.001 for the gastric body, P = 0.0034 for the antrum). Conversely, the percentage of mucosal prostaglandin E2 concentration decrease in each group did not show a significant difference. Famotidine alleviates the reduction of gastric blood flow induced by diclofenac sodium. Further, not only mucosal prostaglandins but also gastric acid may play an important role in non-steroidal anti-inflammatory drugs-induced gastric microcirculatory disturbance.

Postoperative Hyperthermia of Unknown Origin Treated With Dantrolene Sodium

An 11-year-old girl was scheduled for alveolar cleft bone grafting with an iliac bone under general anesthesia. Anesthesia was performed with 70% nitrous oxide, 30% oxygen, and propofol. On the first and second postoperative day, persistent hyperthermia was observed. Because the administration of diclofenac sodium had not been effective for the hyperthermia, dantrolene sodium was given. Her body temperature gradually dropped and returned to normal level on the fifth postoperative day. The hyperthermia in the present case might have been caused by a rapidly elevated muscle metabolism in response to pain and stress after the propofol anesthesia. The oral administration of dantrolene sodium successfully lowered the patient's high body temperature.

A case of severe allergic reaction that was caused by oral administration of diclofenac sodium

A case of severe allergic reaction that was caused by oral administration of diclofenac sodium

Time- and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid.

To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied. Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release. Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Objective: The present study aimed to investigate the possible postnatal effects on the liver, kidney and testicular tissues of the offspring of rats given diclofenac sodium (DS) during pregnancy. Methods: At the beginning of the experiment, 80 rats (20 males and 60 females) were raised together for mating purposes. At the end, 50 pregnant rats were obtained and used as the experimental subjects. All pregnant rats were divided into 2 groups, each with 25 rats. The rats of the control group received physiological serum, 1 cm³/kg live weight per day, and the rats of the treatment group were injected with DS, 1 mg/kg live weight per day from the 5th to the 20th day of pregnancy. Four weeks after birth, tissue samples were obtained under anesthesia by perfusion fixation from a total of 40 offspring, 20 (10 males, 10 females) from the control group and 20 (10 males 10 females) from the DS group. Paraffin sections were dyed with hematoxylin eosin and examined under light microscopy. Results: The gestation period was significantly prolonged with DS-treated rats (p < 0.001). A moderate significant enlargement in the periportal area (p < 0.05), sinusoidal dilatation (p < 0.001), bile duct proliferation (p < 0.001), pyknosis in the nucleus of hepatocytes, and vacuolar degeneration in parenchymal cells (p < 0.001) were observed in DS-treated rats. Morphological changes in the liver were found to be similar both in female and male rats. Under light microscopy a similar morphological structure was observed in the kidney and testicular tissues of both the DS-treated and control rats. Conclusion: Significant morphological changes were observed in the livers of the offspring whose parents had been treated with DS. No significant differences were observed in liver morphology between the female and male offspring. There were no significant effects of DS on the morphology of the kidney and testis in all offspring.

PRELMINARY EVALUATION OF QUERCETIN EFFECT ON DICLOFENAC SODIUM ASSOCIATED GASTRIC ULCER IN RATS.

The effect of quercetin (QRT) in preventing or reducing the diclofenac sodium-induced gastric ulcers was evaluated in rats following over night fasting by using a scanning electron microscopy. The scanning micrographs of stomach specimens showed a marked reduction in the gastric ulceration only when the quercetin is given before the administration of diclofenac sodium. The physicochemical characteristics of diclofenac sodium and quercetin combination were studied using differential scanning calorimetry, IR spectroscopy and X-ray diffractometery. The results revealed that a chemical incompatibility of diclofenac sodium and quercetin undoubtedly has been occurred when they were mixed in one combination. According to aforementioned results, we advise orally taking quercetin only before administration of diclofenac sodium as a prophylactic treatment to protect against its expected gastric disturbances.

Efficacy and Safety of Repeated Postoperative Administration of Intramuscular Diclofenac Sodium in the Treatment of Post-Cesarean Section Pain: A Double-Blind Study

Background Analgesic drugs, either opioids or non-opioids, are required and useful for controlling postoperative pain after cesarean section. Methods The analgesic and opioid-sparing effects of repeated intramuscular (i.m.) injections of 75 mg of diclofenac sodium given immediately after the experiencing of pain following cesarean section under general anesthesia were studied and compared with placebo in a double-blind trial. One hundred twenty patients 18–40 years of age undergoing elective lower segment cesarean section were treated with either 75 mg diclofenac sodium i.m. (60 patients) or identical placebo (60 patients), once patients awakened from anesthesia and experienced wound pain. Their initial responses to either treatment during the first hour after administration of medications were studied. The analgesic, sedative, and opioid-sparing effects of the medications were also studied during the next 48 h. Side effects including uterine relaxation and bleeding were compared between patients administered placebo and diclofenac. Results Results showed that 55/60 patients showed significant pain relief within the first 1 h after administration of diclofenac sodium and their mean pain score decreased from 7.09 ± 1.06 to 0.85 ± 0.8 ( p <0.05). Within the same period, 10/60 patients responded to placebo injections and mean pain score decreased from 6.6 ± 0.96 to 0.8 ± 0.78 ( p <0.05). During the first postoperative 48 h, 45 patients showed complete pain relief with use of diclofenac alone while 15 patients required 2,800 mg of pethidine in addition to diclofenac treatment. All patients using placebo required pethidine injection; the total amount of pethidine used was 22,700 mg per 48 h. Verbal scores for sedation were lower in patients treated with diclofenac than in patients treated with placebo at 6 and 12 h postoperatively ( p <0.05). There were no significant differences in the proportions of patients who required oxytocin infusion due to uterine relaxation in the diclofenac-treated and the placebo-treated groups (7/60 vs. 12/60, p >0.05). Conclusions It might be concluded that repeated i.m. injections of 75 mg diclofenac sodium (maximum two injections per day) could relieve postoperative pain after cesarean section and significantly reduce opioid analgesic requirements without significant effects on uterine relaxation or bleeding during the first postoperative 48 h.

Pharmacokinetic profile of rectally administered diclofenac sodium in children undergoing adenotonsillectomy

Pediatric AnesthesiaVolume 10, Issue 6 p. 694-695 Pharmacokinetic profile of rectally administered diclofenac sodium in children undergoing adenotonsillectomy† D.B. Murphy MD, D.B. Murphy MD Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorP. Kavanagh PhD, P. Kavanagh PhD Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorP. O'Connor FFARCSI, P. O'Connor FFARCSI Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorP. Sherrin FFARCSI, P. Sherrin FFARCSI Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorS. McNamara BSc, S. McNamara BSc Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorB. O'hare FFARCSI, B. O'hare FFARCSI Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this author D.B. Murphy MD, D.B. Murphy MD Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorP. Kavanagh PhD, P. Kavanagh PhD Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorP. O'Connor FFARCSI, P. O'Connor FFARCSI Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorP. Sherrin FFARCSI, P. Sherrin FFARCSI Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorS. McNamara BSc, S. McNamara BSc Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this authorB. O'hare FFARCSI, B. O'hare FFARCSI Our Lady's Hospital for Sick Children, Dublin, Ireland and Department of Pharmacology and Therapuetics, Trinity College Dublin, IrelandSearch for more papers by this author First published: 09 October 2008 https://doi.org/10.1111/j.1460-9592.2000.ab01m.xCitations: 6 † EDITED BY N.S. MORTON Royal Hospital for Sick Children Glasgow, UK Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume10, Issue6November 2000Pages 694-695 RelatedInformation

Pharmacokinetic profile of rectally administered diclofenac sodium in children undergoing adenotonsillectomy

Pharmacokinetic profile of rectally administered diclofenac sodium in children undergoing adenotonsillectomy

Clinical trial on the efficacy and safety of different diclofenac formulations: Multiple-unit formulations compared to enteric coated tablets in patients with activated osteoarthritis

This double-blind, randomised, multicentre study investigated the efficacy and safety of two different dosages of a diclofenac sodium dual release capsule (150 mg or 75 mg once daily) in comparison to a standard treatment with enteric coated tablets (50 mg t.i.d.) and placebo in patients with activated osteoarthritis. Pain relief as the main efficacy variable was measured through 24 hours by means of a Visual Analogue Scale at baseline and on five assessment days during the 12 weeks of treatment. Efficacy was observed in all treatment groups with a statistically significant difference between the verum groups and placebo. The overall safety and tolerability of the active treatments was good. For the 75 mg group, a lower incidence of liver and biliary system-related side effects was reported. Considering efficacy, safety, and compliance aspects, the once daily administration of diclofenac sodium 75 mg dual release capsule is the appropriate dosage regimen for mid- and long-term treatment of osteoarthritis.

Duodenal Ulceration Into the Cystic Artery With Massive Hemorrhage

This is a case presentation of a unique cause of intestinal bleeding. A duodenal ulcer eroded into the superficial branch of the cystic artery, causing massive intestinal hemorrhage. The patient, a 76-year-old woman, presented with left upper abdominal and left back pain secondary to cystic lesions in the pancreas body and tail. Stress after operation and complication of leakage of pancreatic juice after distal pancreatectomy with splenectomy and diclofenac sodium administration may have caused a deep peptic ulcer to erode the cystic artery. We performed a transfixing ligation of the bleeding vessel, serosal suture of ulcer of the gallbladder, and simple closure of the duodenal ulcer with covering greater omentum. There were no serious complications after the operation, and the patient made an uneventful recovery.

A case of Reye's syndrome showing multiple organopathy by Diclofenac sodium administration.

A case of Reye's syndrome showing multiple organopathy by Diclofenac sodium administration.

The absence of any pre-emptive analgesic effect for non-steroidal anti-inflammatory drugs

Pre-emptive analgesic efficacy of the non-steroidal anti-inflammatory drug, diclofenac sodium, was tested in 21 young, fit, patients undergoing third molar extractions in a double-blind, randomised, cross-over, trial. Pain scores and mouth opening were observed for 1 week after the operation and these did not show any differences following pre- and postoperative oral administration of diclofenac sodium 100 mg ( P > 0.05). There were no differences in the patients' preference for the two methods of treatment ( P > 0.05). The study suggests that the non-steroidal anti-inflammatory drug diclofenac sodium does not cause any significant pre-emptive analgesic effects in the dose administered.

Time-Dependent Influence of Diazepam on the Pharmacokinetics of Orally Administered Diclofenac Sodium in Human Subjects

The influence of time of administration on the serum levels of diclofenac when administered alone and in combination with diazepam was studied in 8 healthy human volunteers. The peak serum levels (Cmax) of diclofenac were significantly (p < 0.05) higher (45%) and the mean residence time and apparent steady-state volume of distribution (Vss) were lower (23 and 26%, respectively) after drug administration at 1000h than after administration at 2200h. A significant rise in the mean Cmax of diclofenac when administered concomitantly with diazepam at both 1000h (68%) and 2200h (112%) was observed. In addition, it was interesting to note that diazepam altered pharmacokinetic parameters such as the area under the plasma concentration-time curve (60% increase), clearance (36% decrease) and Vss (24% decrease) of diclofenac to a significant extent (p < 0.05) after the combination treatment at 2200h only. This time-dependent prominence in the effects of diazepam on the pharmacokinetics of diclofenac may be because of the time-dependent effects of diazepam on the physiological functioning of the gastrointestinal tract.