Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes

Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.

Comparison of the effect of stretching exercises and mefenamic acid on the reduction of pain and menstruation characteristics in primary dysmenorrhea: a randomized clinical trial

Objectives: Dysmenorrhea is a common gynecologic disorder. Although non-steroidal anti-inflammatory drugs are commonly used, due to their side effects and lack of response in some individuals, other approaches such as exercise have been considered. This study compared the effect of stretching exercises and mefenamic acid on the reduction of pain and menstruation characteristics in primary dysmenorrhea

Methods: In this randomized clinical trial, 122 female students with moderate to severe dysmenorrheal were assessed and were placed in either the exercise or mefenamic acid group. The exercise program was performed for 15 minutes, three times a week and included a five-minute warm up and six belly and pelvic stretching exercises for 10 minutes. The mefenamic acid group received 250 mg capsules every eight hours from the onset of menstruation until pain relief. Both interventions were performed during two consecutive menstrual cycles. Pain intensity was measured using a 10 cm visual analog scale

Results: The mean pain intensity was significantly higher in the exercise group only in the first cycle [p = 0.058]. In the second cycle, the mean difference in pain reduction in the exercise group was higher than the mefenamic group compared to the start of the study [p = 0.056] and the first cycle [p = 0.007]. There was no significant difference in the severity and duration of pain between the groups [p > 0.050]

Conclusions: Stretching exercises were as effective as mefenamic acid in the treatment of primary dysmenorrhea. Our results suggest that the effect of exercise on relieving menstruation pain increases over time

[Comparison of analgesic effect of valeriana officinalis and mefenamic acid on primary dysmenorrhea]

Background: Primary dysmenorrhea is a common and frequently disabling condition among women in adolescence and reproductive age. Based on results of large epidemiological studies, it is estimated that over a half of the population of young women suffers from dysmenorrhea. Some people are now seeking alternatives to conventional medicine such as herbal drugs. Objective: This study was designed to compare the analgesic effect of Valeriana officinalis with Mefenamic acid in treatment of primary dysmenorrheal

Methods: A randomized, controlled trial was undertaken among 39 female aged 16 to 42 who suffered from primary dysmenorrhea referred to gynecology clinic in Hajar hospital, Shahrekord, Iran. The participants were randomly divided into two groups: Valeriana officinalis [n=18] and Mefenamicacid [n=21]. In intervention group, the patients took350mg Valerian three times a day, and in mefenamic group, the patients took 250 mg Mefenamic three times a day for three days[for three cycles], starting from the onset of bleeding or pain. Participants were followed for three cycles. Main outcome measures was the mean of pain severity at 3 months which recorded by Visual Analogue Scale

Results: There were no significant differences in age, menstural duration, menstural interval, and pain severity score at the beginning of the study in two groups [P>0.05]. After the intervention, findings of the study revealed statistically significant reductions in mean of pain score in Valeriana officinalis [P<0.001] and Mefenamic acid [P<0.001] groups, but this reduction had not significant differences between two groups [P>0.05]

Conclusion: Results shows that valerian has positive effect on treatment of primery dysmenorrheal. More clinical trials are needed to establish the efficacy of Valeriana officinalis in primary dysmenorrheal

Treatment of osteonecrosis of the femoral head by botulinum toxin type A injection to the psoas muscle: A case report

Osteonecrosis of the femoral head (ONFH) can cause femoral head depression and cortical discontinuity. Treatment for ONFH remains challenging. We performed botulinum toxin type A injection to psoas major muscle in five patients with radiological femoral head collapse (Association Research Circulation Osseus classification stage III) who were non-responsive after two years of conservative treatment (tramadol 200 mg/day, mefenamic acid 1,000 mg/day). At two weeks after the procedure, their mean hip pain was decreased from 88 ± 0.4/100 mm to 22 ± 0.4/100 mm based on visual analogue scale (VAS). The pain was maintained at a minimum of 20/100 mm and a maximum of 30/100 mm in VAS for at least six weeks after the procedure. These values were mean ± SD. These patients were followed-up for 6 months. There was no exacerbation of pain from repeated (three times) botulinum toxin type A injection to the psoas major muscle.

Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes

PURPOSE: Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. MATERIALS AND METHODS: Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or 100 microM) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. RESULTS: A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at 100 microM of MEF (38% decrease), providing maximal protection against ionizing radiation. CONCLUSION: The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.

Epidural hematoma after thoracic epidural analgesia in a patient treated with ketorolac, mefenamic acid, and naftazone: a case report / 대한마취과학회지

A 26-year-old male undergoing thoracotomy and bleeding control received a preoperative thoracic epidural for postoperative analgesia. On the fifth postoperative day, paralysis of both lower limbs occurred and urgent magnetic resonance imaging showed massive anterior epidural hematoma. During laminectomy and decompression, platelet dysfunction was diagnosed and preoperative non-steroidal anti-inflammatory drugs medications were supposed to the cause of platelet dysfunction. After infusion of ten units of platelet concentrate, coagulopathy was improved. We should be more careful to drugs with antiplatelet effect when using regional analgesia.

The Effect of Mefenamic Acid and Naproxen on Heavy Menstrual Bleeding: A Placebo-Controlled Study

Background. Heavy menstrual bleeding is a common complaint. Various therapeutic approaches have been suggested.Aim. To compare the efficacy of mefenamic acid and naproxen in reducing heavy menstrual bleeding.Methods. Women referred to an outpatient centre for treatment of heavy menstrual bleeding were recruited. Participants who met the inclusion criteria were evaluated for 6 menstrual cycles. During 3 control cycles they recorded the amount of their bleeding on the Pictorial Blood Assessment Chart to confirm that their menstrual bleeding was heavy. One hundred and twenty participants were then randomly assigned to receive mefenamic acid; naproxen or placebo; and asked to fill in the same questionnaires during 3 intervention cycles. The data were analysed using SPSS version 15 for Windows.Results. Participants receiving mefenamic acid experienced a marked decrease in bleeding during the 3 months of intervention; an initial sharp decrease being followed by a further lesser decrease (p0.05 within group). Bleeding lessened dramatically in the first month of the intervention in participants receiving naproxen; and dropped still further in the second and third months (p0.05 within group). In the placebo group there were slight changes in bleeding during the intervention (p0.05 within group). However; the total decrease in bleeding was greatest in the naproxen arm; and the differences between the groups were statistically significant (p0.05 between groups).Conclusion. All three interventions had positive effects on the mean amount of bleeding; although naproxen was more effective than mefenamic acid and much more effective than placebo

Mefenamic acid-induced bilateral transient myopia, secondary angle closure glaucoma and choroidal detachment.

Drug-induced secondary angle closure is quite common and in the majority of cases simply stopping the medication leads to rapid reversal of the condition and resolution of glaucoma. We describe here a patient who presented with secondary angle closure glaucoma and myopia following mefenamic acid ingestion which was managed successfully by stopping the medication, symptomatic treatment and reassurance.

Comparison of efficacy of oral drotaverine plus mefenamic acid with paracervical block and with intravenous sedation for pain relief during hysteroscopy and endometrial biopsy.

Background : Office hysteroscopy with endometrial biopsy is usually the first investigation for abnormal uterine bleeding and other uterine diseases. Aims: To evaluate the effect of oral drotaverine with mefenamic acid on pain perception during hysteroscopy and endometrial biopsy and to compare it with that of paracervical block using 1% lignocaine and with that of intravenous sedation using diazepam with pentazocine. Settings and Design : Outpatient gynecological department and open randomized trial. Materials and Methods : One hundred twenty women undergoing hysteroscopy and endometrial biopsy were randomized into 3 groups. Group I received tablet containing drotaverine hydrochloride (80 mg) + mefenamic acid (250 mg), group II received lignocaine paracervically and group III received intravenous diazepam. The intensity of pain during the procedure, 30 and 60 minutes later on visual analog scale (VAS) was assessed. Statistical Analysis : Statistical analysis was performed using Kruskal-Wallis test, with the Bonferroni correction, the t test, and the χ2 test. Results: Groups were similar in age, parity, vaginal birth or relevant medical history. A statistically significant difference in pain scores was noted among the 3 groups during the procedure (group I, 4.13± 1.28; group II, 5.93± 1.26; group III, 5.58± 1.51), (P< 0.001); as well as 30 minutes later (group I, 1.78± 0.89; group II, 2.53± 0.81; group III, 2.23± 0.94), (P< 0.001) and 60 minutes later (group I, 1.2± 0.46; group II, 1.98± 0.83; group III, 1.68± 0.75), (P< 0.001). VAS at different time intervals among the groups was also statistically significant. No adverse effects were observed. Conclusions : Oral drotaverine with mefenamic acid is effective in women undergoing hysteroscopy and endometrial biopsy.

[ study on efficacy of NSAIDS in controlling pain caused by orthodontic treatment]

Considering the pain as one of the most significant reasons for patients avoiding orthodontic treatments, the topic of pain control appears to be of prime importance for both clinicians and patients. This study was aimed at determining the efficacy of commonly used non-steroidal anti- inflammatory drugs [NSAIDs] in controlling pain following orthodontic procedures. This was a double-blind clinical trial performed on a total of 75 patients, randomly divided into 5 groups following the placement of their initial arch wires. The members of each group received one of the 5 different treatments [Ibuprofen 400 mg, Naproxen 250 mg, Mefenamic acid 250 mg, Aspirin 325mg, and starch as placebo]. After receiving 2 doses of drugs [one hour before and six hours after bonding] the patients indicated the severity of their pain on a 100mm horizontal line [VAS] during mastication, biting, fitting on anterior and posterior teeth in different specified times. Statistical analyses were carried out based on ANOVA and t-test. The pain increased soon after the placement of the arch wire and reached its peak in 24 hours. In all cases, the least pain was reported following the administration of Ibuprofen and the most after taking placebo. Although all NSAIDs were more or less effective in controlling pain, ibuprofen was found to be relatively of higher efficacy in decreasing the pain

Growth inhibition of oral squamous cell carcinorma cell line induced by cox inhibitor

COX-2 inhibitor induced apoptosis in oral squamous cell carcinoma cell line through AKT pathway

Comparison of therapeutic effects of fennelin and mefenamic acid on primary dysmenorrhea

Dysmenorrhea is one the most common disorders in Gynecology, which occurs in 50% of women with regular menstrual cycls. There have been various treatment methods regarding this, among which the drugs with less side effects are preferred. The purpose of the present study, is to compare the effect of Fennelin and Mefenamic Acid on primary dysmenorrhea. This research is the result of an experimental study at the level of a double-blind clinical trial in 2006. In this study, 104 students with moderate to severe primary dysmenorrhea were randomly selected and assigned into 3 drug-taking groups, including Fennelin [36], Mefenamic Acid [36] and Placebo [32]. They were assigned to receive the relevant drugs in two successive menstrual cycles at the beginning of the pain. The selected subjects were asked to fill out the questionnaires regarding the severity of pain, hemorrhage and clinical problems in the first visit, during the first five hours, 48 hours and the first three days in two successive cycles. There were no significant differences between the 3 selected groups regarding the age and the characteristics of menstruation. The average age of the subjects was 20.7 +/- 0.16 and the average age of the beginning of primary dysmenorrhea was 15.11 +/- 0.26. 71.2% of subjects had moderate while 28.8% with severe dysmenorrhea. The pain severity highly decreased in Fennelin takers compared with the Placebo takers, and as the time of treatment continued, this difference increased. However, there was no significant difference between the Fennelin and Mefenamic Acid takers. The effect of Fennelin was also more than Mefenamic Acid in reducing the severity of hemorrhage. There was no significant difference between the 3 groups regarding the clinical symptoms, but there was considerable reduction in the severity of clinical problems in Fennelin takers compared with the two other groups. According to the drug-takers, Fennelin was more effective in reducing the complaints compared with Placebo; however, it had no significant difference from Mefenamic Acid. The effect of Fennelin in relieving primary dysmenorrhea is not less than Mefenamic Acid, and it can be useful in reducing the severity of pain, hemorrhage and clinical symptoms. Therefore, due to the safety of herbal drugs, it can replace the chemical drugs

[Comparing ginger with mefenamic acid and ibubrofen for the treatment of primary dusmenorrhea]

Primary dysmenorrhea is a frequent entity with known side effects on life quality. Ginger has been shown to inhibit prostaglandins, thus, the present study was designed to compare ginger with mefenamic acid and ibubrofen for the treatment of primary dysmenorrhea in a group of students in dormitories affiliated to Isfahan and Shahid Beheshti University of Medical Sciences. For this double-blinded clinical trial, 150 students with primary dysmenorrhea were enrolled. Subjects were matched according to dysmenorrheal severity, then, assigned in 3 equal groups of ginger [250mg], mefenamic acid [250mg], and ibubrofen [400mg] that were all prescribed 4 times a day for 3 days. Groups were matched according to the following criteria: age, age of menarche onset, weight, height, BMI, father's position, maternal occupation and level of education, regular exercise, and duration, interval and amount of menses' bleeding. Finally, verbal multidimensional scoring system was used to assess the efficacy of drugs on dysmenorrhea. ANOVA and chi square were used for data analysis. Dysmenorrheal improvement did not differ significantly among ginger [64%], mefenamic acid [58%] and ibubrofen [66%] groups. Thus, ginger is as effective as mefenamic acid and ibubrofen in alleviating dysmenorrheal symptoms. Ginger is an effective drug for alleviating primary dysmenorrheal symptoms

Comparison of the effectiveness of fennel and mefenamic acid on pain intensity in dysmenorrhoea

A study in Kerman, Islamic Republic of Iran in 2002 compared the effectiveness of fennel and mefenamic acid on pain relief in primary dysmenorrhoea. Two groups of high-school girls [mean age 13 years] suffering dysmenorrhoea were randomized to receive fennel extract [n = 55] or mefenamic acid [n = 55] for 2 months. In the fennel group, 80% of girls and in the mefenamic acid group, 73% of girls showed complete pain relief or pain decrease, while 80% in the fennel group and 62% in the mefenamic acid group no longer needed to rest. There was no significant difference between the 2 groups in the level of pain relief

[Comparison between the pain-relief effect of fennel and mefenamic acid on primary dysmenorrhea]

Dysmenorrhea is a painful menstruation, usually cramping in nature and centered in the lower abdomen. About 60% of menstruating adolescence were reported to have some degrees of dysmenorrhea and 14% regualry missed school. This semi-experimental single-blinded study was conducted to compare the effects of fennel and mefenamic acid on the severity of pain in primary dismenorrhea. The assessment was performed on 110 volunteers at high school age [Kerman province 1381]. Samples were categorized into two groups which received either fennel or mefenamic acid. Regarding the age of menarch and beginning of dysmenorrhea, there was no significant statistical difference between these two groups. The number of cases who were compeletely or partially cured, were 44 [80%] and 40 [73%] in fennel and mefenamic acid groups, respectively. At the end of the treatment, 44 subjects [80%] in fennel group and 34[62%] subjects in mefenamic acid group needed no rest. Totally, there was no significant statistical difference between these two groups. However, due to safety of herbal drugs, chemical agents can be replaced with herbal drugs

Comparison of the effects of vitamin E and mefenamic acid on the severity of primary dysmenorrhea

Primary dysmenorrhea has relatively high incidence which can influence the well being and activities of the sufferers. An experimental cross-over study was designed to compare the effectiveness of vitamin E and mefenamic acid on reducing the severity of dysmenorrheal symptoms. Eighty six female medical students, aged between 18-26 who were suffering from primary dysmenorrhea were recruited. After having written consent they were divided into two groups of 43 individuals who received 500 units of vitamin E [2 tablets of 400 and 100 units] and 750mg mefenamic acid [250mg IDS] per day respectively. Treatment with vitamin E was started 2 days before the beginning of menstruation and continued until the first day of bleeding [3 days in total] and mefenamic acid was administered only during the first 48 hours of menstruation [only two days] Severity of pain, duration of bleeding, duration of menstruation and other symptoms such as diarrhea, secondary nausea, vomiting, vertigo, headache, legache, epigastric pain, pelvic pain before and after the treatment were recorded. Severity of pain was monitored by visual analogue scale [VAS] method on a visual scale. Monitoring was carried out for 2 consecutive cycles in both groups. Crossover was carried out and observation was continued for another 2 cycles. The result of this study indictate that both vitamin E and mefenamic acid could reduce the severity of pain similarly nevertheless but vitamin E consumption, complications such as digestive disorders such aspyrosis, stomach-ache, nausea and fatigue were significantly less compared to mefenamic acid. It appears that mefenamic acid could be replaced by vitamin E in reducing complications of dysmenorrhea

Renal humoral modulation of skeletal muscle tone in mice: implications for 'the pulmonary-renal cascade'.

The pulmonary-renal cascade may regulate the respiration and skeletal muscle contractility. To evaluate this working hypothetical model, we conducted experiments to ascertain the skeletal muscle tone of the Swiss mice (20-35 g). The animals were evaluated for their skeletal muscle tone via several techniques i.e. inclined plane test, grip strength test and swim test. Groups of mice (n=6) were pre-treated with mefenamic acid (60 mg/kg, i.p), carbenoxolone (100 mg/kg i.p) or vehicle only 15 minutes before the treatment with heparin (500 U/kg, i.v), urokinase (5500 U/kg, i.v) and erythropoietin (150 U/kg, i.v). Heparin potentiated the loss of skeletal muscle tone induced by mefenamic acid and carbenoxolone while urokinase & erythropoietin significantly enhanced the skeletal muscle tone as evaluated by all or one of the tests. Other groups of mice (n=6) were pretreated with mefenamic acid (1 mg i.c.v), carbenoxolone (160 microg i.c.v) or minoxidil (30 microg i.c.v) and the effects of heparin & urokinase and erythropoietin on skeletal muscle tone were evaluated. To study the effects of heparin and urokinase on nerve regeneration, two groups of mice underwent a sham and sciatic nerve crush procedure. The mice treated with urokinase recovered much faster as compared to those treated with heparin or saline. These experimental results suggest that gap junction blockers and potassium channel openers interact with heparin, urokinase and erythropoietin to control the skeletal muscle tone.