Synthesis of a PVA drug delivery system for controlled release of a Tramadol-Dexketoprofen combination.

The local administration of analgesic combinations by means of degradable polymeric drug delivery systems is an alternative for the management of postoperative pain. We formulated a Tramadol-Dexketoprofen combination (TDC) loaded in poly(vinyl alcohol) (PVA) film. Films were prepared by the solvent casting method using three different molecular weights of PVA and crosslinking those films with citric acid, with the objective of controlling the drug release rate, which was evaluated by UV-vis spectrometry. Non-crosslinked PVA films were also evaluated in the experiments. Differential scanning calorimetry (DSC) analysis of samples corroborated the crosslinking of PVA by the citric acid. Blank and loaded PVA films were tested in vitro for its impact on blood coagulation prothrombin time (PT) and partial thromboplastin time (PTT). The swelling capacity was also evaluated. Crosslinked PVA films of higher-molecular weight showed a prolonged release rate compared with that of the lower-molecular-weight films tested. Non-crosslinked PVA films released 11-14% of TDC. Crosslinked PVA films released 80% of the TDC loaded (p < 0.05). This suggests that crosslinking films can modify the drug release rate. The blank and loaded PVA films induced PT and PTT in the normal range. The results showed that the polymeric films evaluated here have the appropriate properties to allow films to be placed directly on surgical wounds and have the capacity for controlled drug release to promote local analgesia for the control of postoperative pain.

Acetaminophen and tramadol hydrochloride-loaded soft gelatin capsule: preparation, dissolution and pharmacokinetics in beagle dogs.

The objective of this study was to develop a novel acetaminophen and tramadol hydrochloride-loaded soft capsule (ATSC) with enhanced bioavailability of tramadol. The ATSC was manufactured in a pilot-scale batch size with the capsule contents composed of tramadol, acetaminophen, PEG 400 and Capmul MCM at a weight ratio of 37.5:325:177.5:30. Moreover, its dissolution, stability and pharmacokinetics in beagle dogs were carried out compared to commercial tablet. The dissolved amounts of acetaminophen from the ATSC and commercial tablet were not significantly different. However, compared to the latter, the former had significantly higher dissolution rate of tramadol at the initial times. In beagle dogs, the ATSC provided no significant difference in plasma concentrations and AUC of acetaminophen than did the commercial tablet; however, it significantly improved those of tramadol compared to the other, indicating the enhanced oral bioavailability of tramadol. Compared to the commercial tablet, the ATSC had a larger AUC value for tramadol (55.27 ± 11.06 vs. 92.62 ± 21.52 h·ng/ml). In the accelerated long-term stability, the ATSC offered higher than 96% drug content of acetaminophen and tramadol, suggesting that it was stable for at least six months. Therefore, this ATSC would be a recommendable candidate with enhanced oral bioavailability and excellent stability.

Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.

AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. METHODS: We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours. RESULTS: The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points. CONCLUSION: Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.

Effect of Submucosal Injection of Tramadol on Postoperative Pain After Third Molar Surgery.

PURPOSE: This study aimed to evaluate the effectiveness of submucosal injection of tramadol in treating postoperative pain after surgical extraction of impacted mandibular third molars. MATERIALS AND METHODS: We implemented a randomized controlled trial. The sample was divided into 30 cases (receiving tramadol injection) and 30 controls (receiving saline solution injection). Patients were asked to complete a visual analog pain scale (VAPS) at 0.5, 1, 2, 4, 6, 12, 24, and 48 hours. Patients also were asked to note the time at which rescue analgesics were taken, as well as the total number of analgesics taken. The VAPS data were analyzed using the unpaired Student t test. Other variables were analyzed using analysis of variance with the Bonferroni t test and Pearson χ2 test. P < .05 was considered significant. RESULTS: A total of 60 patients, 32 men and 28 women (mean age, 27.78 years; age range, 19 to 45 years), took part in this study. Postoperative pain scores, as recorded on the VAPS, were significantly lower in the tramadol group, with the differences being statistically significant at 0.5, 1, 2, 4, and 6 hours (P < 0.001, P = .006, P < 0.001, P < 0.001, and P < 0.001, respectively). The mean time at which the first tablet was taken and the total number of tablets taken by the tramadol group also were statistically significant (P = .001 for both). CONCLUSIONS: The results suggest that submucosal injection of tramadol has a significant effect on postoperative pain control after surgical extraction of impacted third molars.

Analgesic efficacy of ketorolac associated with a tramadol/acetaminophen combination after third molar surgery - a randomized, triple-blind clinical trial.

BACKGROUND: This study compared the efficacy of ketorolac alone versus its combination with tramadol/acetaminophen for pain control after mandibular third molar surgery. MATERIAL AND METHODS: A randomized, triple-blind clinical trial was carried out with 52 patients divided into 2 groups: Group K+T+A (1 tablet of Ketorolac 10 mg plus and 1 capsule of Tramadol 37.5 mg/acetaminophen 325 mg) and Group K (1 tablet of Ketorolac 10 mg plus and 1 placebo capsule). The treatments were given 1 h before the surgery and was repeated 4 times per day, for 48 h. The difference in postoperative pain was assessed by 4 primary end-points: pain intensity (VAS 100mm, for 48 h), rescue medication, overall assessment and adverse effects. RESULTS: Significant differences in pain intensity were observed in the different times (p < 0.05). The comparison of groups in each time showed significant differences only of 9 h, with lower level of pain intensity for group K+T+A (p = 0.005). The need of analgesics was higher in Group K (p < 0.001), the need of antiemetic were greater in Group K+T+A (p < 0.0001). No significant difference between groups were observed in overall assessment. The adverse effects was higher in Group K+T+A. CONCLUSIONS: The current study showed that both ketorolac and the combination of ketorolac plus tramadol/acetaminophen showed good control of pain after the extraction of the lower third molars. Although the combination group showed lower pain at 9 h, the difference is small and not clinically relevant.

Comparison of Local Anesthetic Efficiency of Tramadol Hydrochloride and Lidocaine Hydrochloride.

PURPOSE: This study investigated the local anesthetic efficiency of tramadol versus lidocaine hydrochloride in maxillary infiltration anesthesia. MATERIALS AND METHODS: This study was a randomized double-blinded study involving 50 healthy volunteers. In the experimental part of this study, each volunteer received a buccal 0.5-mL injection of tramadol hydrochloride 25 mg on one side and a buccal 0.5-mL injection of vasoconstrictor-free lidocaine hydrochloride 20 mg on the other side. No other treatment was performed. After the injections, total duration of anesthesia, start and finish times of anesthesia, soft tissue (sensory) innervation, depth of anesthetic, possible side effects, and satisfaction levels were recorded from all volunteers. RESULTS: There was no relevant difference between solutions for total anesthesia duration and peak values. However, statistically, the effect of lidocaine started and ended early. The efficacy of tramadol was markedly more effective in the gingiva and skin, especially at 15 and 20 minutes, compared with lidocaine. Both anesthetic agents were well tolerated by the volunteers. CONCLUSION: Tramadol hydrochloride can be a good alternative to local anesthetic agents and beneficial to support anesthesia during long operations.

Comparative Analgesic Effects of Ibuprofen, Celecoxib and Tramadol after third Molar Surgery: A Randomized Double Blind Controlled Trial.

BACKGROUND: This study compared the effects of ibuprofen, celecoxib and tramadol on pain after surgical extraction of impacted mandibular third molars. PATIENTS AND METHODS: This double blind randomized controlled trial recruited 135 healthy subjects who required surgical extraction of impacted mandibular third molars, with a mean age of 26.51 ± SD 6.29 years. The subjects were randomized into three equal groups and given appropriate doses of each drug immediately after extraction. They continued the drugs up to 48 hours after extraction. Postoperative pain intensity was self-recorded by subjects at 4, 8, 16, 24 and 48 hours after extraction, using visual analogue scale (VAS). Data analysis involved descriptive statistics, 2-sample Wilcoxon Mann-Whitney U test and Kruskal Wallis rank test. Statistical analysis was done using intention-to-treat analysis. The mean VAS at each point of postoperative pain assessment was compared using one way analysis of variance (ANOVA) among the three groups. Statistical significance was inferred at p < 0.05. RESULTS: The mean VAS score of the celecoxib group (32.35± SD 23.96) at 4 hours was the lowest among the three groups. This was followed by the ibuprofen group with mean VAS score of 38.96 ± SD 22.30. Whereas, the subjects in tramadol group experienced the highest VAS score (53.31 ± SD 23.30) at 4 hours. There was statistically significant difference in the mean VAS scores at 4 hours after extraction when the three groups were compared (p = 0.0039). Celecoxib group also had the lowest mean VAS scores at 8 hours, 24 hours and 48 hours after the extraction. None of the subjects in the ibuprofen and celecoxib groups reported any adverse effect of the analgesics, whereas 47.61% of the tramadol group did. CONCLUSION: Celecoxib was the most effective analgesic of the three studied drugs in controlling postoperative pain after mandibular third molar extraction in our subjects. It was closely followed by ibuprofen while tramadol was found to be the least effective. CLINICAL SIGNIFICANCE: The outcomes of this study suggest that celecoxib can be prescribed for effective control of postoperative pain after third molar surgery especially in patients with peptic ulcer disease who will not tolerate the adverse effect of traditional nonsteroidal anti-inflammatory drugs. It also shows that ibuprofen can be an analgesic of choice for patients who are not at risk of gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Tramadol could be considered for patients with milder postoperative pain after third molar surgery.

Evaluation of Effect of Glucosamine-Chondroitin Sulfate, Tramadol, and Sodium Hyaluronic Acid on Expression of Cytokine Levels in Internal Derangement of Temporomandibular Joint.

AIM: Evaluation of the effect of glucosamine-chondroitin combination, tramadol, and sodium hyaluronic acid in temporomandibular joint (TMJ) disorders and its impact on the expression of various cytokines such as IL-6, IL-1ß, TNF-α, and PGE2. MATERIALS AND METHODS: The present study was conducted on 60 patients (males-30, females-30) suffering from internal derangement such as disc displacement with reduction of TMJ. The patients were divided into three groups of 20 each. Group I received a combination of 1.5g of glucosamine and 1.2 g of chondroitin sulfate per day and group II received 50 mg tramadol HCL peroral. Group III received sodium hyaluronate 10 mg/mL, 2 mL injection syringe on each joint. Pain (VAS) scale and maximum mouth opening (MMO) was measured. The level of IL-6, IL-1ß, TNF-α, and PGE2 levels were measured using Enzyme-linked immuno sorbent assay (ELISA). RESULTS: There was an improvement in maximum mouth opening in all three groups (p < 0.05). There was a reduction in pain in all groups. IL- 1ß, TNF-α, and PGE2 leve ls showed reduction while IL-6 showed an increase in value in group II and III. CONCLUSION: The efficacy of glucosamine chondroitin sulfate , tramadol and hyaluronic acid in TMJ disorders has been found to be effective. CLINICAL SIGNIFICANCE: IL-6, IL-1ß, TNF-α, and PGE2 levels indicate the risk of TMJ disorders. Thus earlier assessment of their levels helps in diagnosis, and better management may be done.

Development of solid-phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer.

In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid-phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid-phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL-1 ) and 10 ppm (10 µg mL-1 ) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12-107.54% in aqueous solution and 76.16-91.20% in rabbit brain tissue. The inter- and intra-day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost-effective sample analysis.

The effect of preoperative submucosal administration of tramadol on the success rate of inferior alveolar nerve block on mandibular molars with symptomatic irreversible pulpitis: a randomized, double-blind placebo-controlled clinical trial.

AIM: This randomized, double-blind, placebo-controlled, clinical trial was designed to improve the success of inferior alveolar nerve blocks (IANB) in mandibular molars with symptomatic irreversible pulpitis (SIP) by means of preoperative submucosal administration of 50 mg tramadol. METHODOLOGY: Forty-two patients with a mandibular molar diagnosed with SIP took part in the trial. Patients were assigned randomly to one of two groups: tramadol group (n = 21), who received 50 mg tramadol in 1 mL by mandibular infiltration, and a placebo group (n = 21), who received 1 mL of normal saline administered to the affected tooth by the same means. Ten minutes later, all patients received an IANB with 4% articaine with epinephrine 1 : 100 000. A 10-min waiting time was established after local anaesthetic (LA) administration before carrying out three consecutive tests to assess anaesthesia of the pulp, that is two consecutive negative responses to an electric pulp test, positive or negative response to a cold test and no pain during access cavity preparation. IANB was considered successful only if the patient did not experience pain arising from these tests. Data were analysed by the Chi-squared frequency test and the Fisher's exact test, for qualitative variables, Mann-Whitney U-test for independent samples and two-way anova for more than two independent samples. RESULTS: In the tramadol group IANB was achieved successfully in 57% of the sample, whilst the placebo group obtained 29%. The difference between groups was not significant (P = 0.06). When performing endodontic access, the anaesthetic success rate was significantly in favour of tramadol (P = 0.03). CONCLUSIONS: Preoperative submucosal administration of 50 mg tramadol in mandibular molars with SIP significantly improved the success of IANB using 4% articaine with 1 : 100 000 epinephrine during access cavity preparation in comparison with a placebo.

Neutrophil lymphocyte ratio predicts postoperative pain after orthognathic surgery.

BACKGROUND AND AIM: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil-lymphocyte ratio (NLR) - as an inflammation marker - and postoperative analgesic demand in patients underwent orthognathic surgery. MATERIALS AND METHODS: We retrospectively investigated medical and anesthesia records of 177 patients underwent orthognathic surgery. Demographical data, preoperative NLR, type of surgery, modified Mallampati score, difficulty degree of intubation, duration of surgery, and postoperative analgesic (tenoxicam - as the first drug of choice, paracetamol, tramadol, or pethidine) usage were recorded. A cutoff value of NLR ≥2 was determined for inflammation threshold. Two groups (Group 1 NLR ≥2, Group 2 NLR <2) were compared for analgesic doses, numbers of patients needed analgesic treatment, and other parameters. RESULTS: Mean administered tenoxicam dose was significantly higher in Group 1 than in Group 2 (P < 0.0001). Further, ratio of patients treated with tenoxicam in Group 1 was significantly higher than that in Group 2 (χ2 = 4.779, P = 0.029). CONCLUSIONS: Preoperatively measured NLR may help to predict postoperative analgesic demand in patients undergoing orthognathic surgery, and thus sufficient postoperative pain control can be achieved with various preventive treatments taken at the perioperative period such as preemptive analgesia, local anesthetic administration at the end of surgery, or early administration of analgesics.

Analgesic efficacy of an oral transmucosal spray formulation of meloxicam alone or in combination with tramadol in cats with naturally occurring osteoarthritis.

OBJECTIVE: To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). STUDY DESIGN: Randomized, blinded study. ANIMALS: Fifteen geriatric cats weighing 4.5 ± 1.0 kg. METHODS: Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg-1 every 24 hours) (group M, n = 7), or tramadol (3 mg kg-1 every 12 hours orally) and meloxicam OTMS (group TM, n = 8) for 25 days. Evaluations performed before treatment (D0) and at week 3 (W3) consisted of peak vertical force, motor activity and response to mechanical temporal summation of pain (RMTS). Data were analyzed with mixed models and Fisher's exact test. RESULTS: Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.

Designing and characterizing of tramadol hydrochloride transdermal patches prepared with Ficus carica fruit mucilage and povidone.

The purpose of this investigation was to prepare matrix type transdermal patches of Tramadol HCl using various ratios of Ficus carica fruit mucilage and Povidone. The matrix type transdermal patches were prepared using Tramadol HCl with Ficus carica fruit mucilage and Povidone. The interactions between Tramadol HCl with F. carica fruit mucilage and Povidone were performed by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The prepared patches were examined for physicochemical characterization and in vitro drug permeation studies (using a Keshary-Chien diffusion cell across hairless Albino rat skin), skin irritation studies and accelerated stability studies. The drug was found to be free from negligible interactions with the polymers used. The formulated patches possessed satisfactory physicochemical properties, in vitro drug permeation and devoid of serious skin irritation. The selected formulation (F-5) was retains the characteristics even after the accelerated environmental conditions. The study concludes that F. carica fruit mucilage with Povidone is a good combination for preparing transdermal patches.

Tramadol for premature ejaculation: a systematic review and meta-analysis.

BACKGROUND: Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in breathing and the beneficial effect of tramadol in PE is yet not supported by a high level of evidence. The purpose of this study was to systematically review the evidence from randomised controlled trials (RCT) for tramadol in the management of PE. METHODS: We searched bibliographic databases including MEDLINE to August 2014 for RCTs. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. Between-group differences in IELT and other outcomes were pooled across RCTs in a meta-analysis. Statistical and clinical between-trial heterogeneity was assessed. RESULTS: A total of eight RCTs that evaluated tramadol against a comparator were included. The majority of RCTs were of unclear methodological quality due to limited reporting. Pooled evidence (four RCTs, 721 participants), suggests that tramadol is significantly more effective than placebo at increasing IELT over eight to 12 weeks (p = 0.0007). However, a high level of statistical heterogeneity is evident (I-squared = 74%). Single RCT evidence indicates that tramadol is significantly more effective than paroxetine taken on-demand, sildenafil, lidocaine gel, or behavioural therapy on IELT in men with PE. Tramadol is associated with significantly more adverse events including: erectile dysfunction, constipation, nausea, headache, somnolence, dry mouth, dizziness, pruritus, and vomiting, than placebo or behavioural therapy over eight to 12 weeks of treatment. However, addiction problems or breathing difficulties reported by patients for PE is not assessed in the current evidence base. CONCLUSIONS: Tramadol appears effective in the treatment of PE. However, these findings should be interpreted with caution given the observed levels of between-trial heterogeneity and the reporting quality of the available evidence. The variability across placebo-controlled trials in terms of the tramadol dose evaluated and the treatment duration does not permit any assessment of a safe and effective minimum daily dose. The long-term effects and side effects, including addiction potential, for men with PE have not been evaluated in the current evidence base. TRIAL REGISTRATION: The review is registered on PROSPERO 2013: CRD42013005289 .

Comparison of the Effects of Topical Ketamine and Tramadol on Postoperative Pain After Mandibular Molar Extraction.

PURPOSE: This study compared the analgesic efficacy of postoperative tramadol versus ketamine for preventing pain after mandibular molar extraction. PATIENTS AND METHODS: Ninety patients who had undergone molar extraction were randomly divided into 3 groups: group T (tramadol 1 mg/kg), group K (ketamine 0.5 mg/kg), and group P (saline 2 mL). The treatment was applied to the extraction sockets using resorbable gelatin sponges. Pain after extraction was evaluated using a visual analog scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 hours postoperatively. RESULTS: The VAS scores after extraction were statistically higher in group P than in either treatment group. Group K had the lowest pain intensity. CONCLUSION: This study shows that topical tramadol and ketamine are effective alternatives for decreasing pain after molar extractions.

Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets.

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083-6 h) with a Tmax at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies.

Design, development and in vitro-in vivo study of tramadol-paracetamol inlay tablets.

The objective of this work is to formulate, optimize and evaluate in-lay tablets of tramadol-paracetamol. This study investigated the effect of hydrophobic, plastic and hydrophilic types of polymers and their content level on release profile of a highly water-soluble drug tramadol hydrochloride. A 3(2) full factorial design was employed for the optimization of the sustained release (SR) formula of tramadol hydrochloride using ethyl cellulose, eudragit and carbopol. CP9 (66% carbopol and compression load of 6 ton) with a percentage drug release of 89.03 after 12 hours were found to be most comparable to the marketed product in terms of similarity factor and most appropriately fits to zero-order kinetics. Hence, it was selected for in vivo study. Statistical analysis of in vivo studies showed that the plasma drug level after oral administration from the prepared formulation is almost comparable to the marketed product (p < 0.05). Pharmacokinetic analysis of the optimized tablet formulation CP9 were done to find out relevant pharmacokinetic parameters. The results showed that Cmax, tmax, AUC, AUMC, MRT were comparable to the marketed preparation. The formulation exhibited a good in vitro-in vivo correlation (r(2) = 0.971).

Effects of three oral analgesics on postoperative pain following root canal preparation: a controlled clinical trial.

AIM: To compare the effects of single doses of three oral medications on postoperative pain following instrumentation of root canals in teeth with irreversible pulpitis. METHODOLOGY: In this double-blind clinical trial, 100 patients who had anterior or premolar teeth with irreversible pulpitis without any signs and symptoms of acute or chronic apical periodontitis and moderate to severe pain were divided by balanced block random allocation into four groups of 25 each, a control group receiving a placebo medication, and three experimental groups receiving a single dose of either Tramadol (100 mg), Novafen (325 mg of paracetamol, 200 mg ibuprofen and 40 mg caffeine anhydrous) or Naproxen (500 mg) immediately after the first appointment where the pulp was removed, and the canals were fully prepared. The intensity of pain was scored based on 10-point VAS before and after treatment for up to 24 h postoperatively. Data were submitted to repeated analysis of variance. RESULTS: At the 6, 12 and 24 h postoperative intervals after drug administration, the intensity of pain was significantly lower in the experimental groups than in the placebo group (P < 0.01). Tramadol was significantly less effective (P < 0.05) than Naproxen, and Novafen that were similar to each other (P > 0.05). CONCLUSION: A single oral dose of Naproxen, Novafen and Tramadol taken immediately after treatment reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis.

Double-phase hydrogel for buccal delivery of tramadol.

CONTEXT: Treatment of chronic pain is complicated by the evidence that abuse of prescription opioids is rising; therefore, in many cases, chronic pain remains undertreated. Tramadol is an atypical central analgesic with a mixed mechanism of action offering many advantages over conventional opioids. OBJECTIVE: We exploited the nonopioid action of tramadol, by bypassing the first-pass effect, as well as multiparticulate drug delivery. Our aim was to identify optimal formulation parameters for designing polyvinyl alcohol (PVA), single and mixed dual cross-linked tramadol microspheres-loaded hydrogel with adequate bioadhesion and providing controlled drug release for buccal delivery. METHODS: Microspheres characterization was done by scanning electron microscopy and infrared spectroscopy. Other investigations comprised the evaluation of yield, drug content, particle size, rheology, swelling, mucoadhesion, release, and permeation studies through biological membranes all together with testing the antinociceptive activity and its attenuation by the antagonist naloxone HCl. RESULTS AND CONCLUSION: PVA-alginate microspheres (F3)-loaded carbopol hydrogel attained: the highest mucoadhesion time (1436.67 min ± 5.77) and mucin adsorption capacity, shear thinning thixotropic properties with adequate yield value and hysteresis area, best drug release (RE = 84.20 ± 2.07%) and permeation efficiency (PE = 65.30 ± 7.02%). Dissolution and permeation profiles were compared using similarity factor; F3-loaded carbogel had the lowest value. During in vivo study, the nonsignificant difference between the AUC of the groups receiving F3-loaded carbogel buccally with (group 5) and without (group 4) administration of naloxone, and between group 4 and the oral group, showed that the buccal route may arguably provide an alternative safer route of tramadol administration.

Analgesic efficacy of tramadol and butorphanol in mandibular third molar surgery: a comparative study.

BACKGROUND: Butorphanol tartrate, a mixed synthetic agonistantagonist opioid analgesic has been used for management of postoperative pain in minor and major surgical procedures.(14,20) Tramadol hydrochloride is a centrally acting opioid which is effectively used in postoperative pain in various minor and major surgeries. MATERIALS AND METHODS: Twenty subjects selected randomly received butorphanol tartrate 1 mg intramuscular and 20 subjects received tramadol hydrochloride 50 mg intramuscular after the removal of mandibular third molars. Time of injection, amount of anesthetic injected, duration of surgery, adverse effects were recorded.(21) RESULTS: The mean amount of LA administered in butorphanol group was 2.6450 ml and in tramadol group was 2.640 ml respectively, the mean duration for surgery was 56.75 and 53.5 minutes for butorphanol and tramadol groups respectively which was statistically not significant. Pain assessment was done with VAS which showed mean of 19.2 and 15.5 mm (p = 0.001) which was significant for butorphanol and tramadol respectively after 12 hours. The mean time for rescue medication requirement was 5.9 hours (for tramadol) and 8.4 hours (for butorphanol). Effective analgesic activity was seen by butorphanol 1 mg intramuscular then tramadol 50 mg. CONCLUSION: Butorphanol 1 mg was more effective than tramadol 50 mg in respect to postoperative analgesia.