Tramadol Hydrochloride Tablets Research Articles

Eco-friendly simultaneous multi-spectrophotometric estimation of the newly approved drug combination of celecoxib and tramadol hydrochloride tablets in its dosage form

Food and Drug Administration (FDA) recently approved co-formulated celecoxib and tramadol for the treatment of acute pain in adults. Three spectrophotometric methods were efficiently applied to estimate the co-formulated Celecoxib and Tramadol in their tablets; second derivative 2D-spectrophotometry technique (method I), induced dual-wavelength technique (method II) and dual-wavelength resolution technique (method III). The proposed methods were successfully validated following the International Council for Harmonisation (ICH) guidelines and statistically assessed based on the correlation coefficients, relative standard deviations as well as detection and quantitation limits. The obtained results revealed non-significant differences compared to the reported results as revealed by the variance ratio F test and Student t test. Moreover, the applied techniques were further assessed concerning their greenness based on the analytical eco-scale method revealing an excellent green scale with a final score of 95. The proposed spectrophotometric techniques could be applied for the routine analysis and quality control of the studied drugs in their dosage form.

SELECTION AND OPTIMIZATION OF MOST EFFICIENT SUPERDISINTEGRANT FOR THE FORMULATION OF DISPERSIBLE TABLETS OF TRAMADOL HYDROCHLORIDE

Objective: The intent and objective of this research work were to find out the most effective superdisintegrants on the basis of disintegration time dissolution rate and other secondary tablet properties among the three mostly used superdisintegrants (Crospovidone, sodium starch glycolate and croscarmellose). This endeavour was initiated to mitigate dysphagia and for better bioavailability of drugs. Methods: Nine formulations of Tramadol HCl (50 mg) dispersible tablets were fabricated by direct compression process using different concentrations (3%, 5% and 8%) of mentioned superdisintegrants. Dispersible tablets were formulated and evaluated for various parameters such as thickness, hardness, friability, weight variation, disintegration time, drug content and dissolution rate. Then the stability study was carried out on the selected formulation batch to get a conclusion. Results: Results were interpreted in mean±SD where the value of n is equal to 3. The formulated dispersible tablets were evaluated for their post-compression parameters after achieving the desired pre-compression attributes. In pre-compression evaluation, the flow property and compressibility of powder were checked and the results found to be acceptable of all the nine formulations having an angle of repose less than 19 °, compressibility index in the range of 14.45 to 15.27 and Hausner’s ratio (≤ 1.29). The thickness of the tablets was found to be 4.19 to 4.28 mm. The tablets have optimum hardness just above 4 kg/sq. cm for better sustainability against mechanical stress and the percentage loss on friability found to be less than 1%. The drug content in the tablets of all nine formulations was found to be in the range of 97.48±0.9% to 99.46±0.4%. The wetting time and disintegration time were found to be within 20 sec and 40 sec, respectively, for all nine batches. The dissolution profile showed that more than 97% of the drug were released within 14 min, which is a great achievement in comparison to marketed dispersible tablets. The formulation batch (B2) with crospovidone as superdisintegrant has shown supremacy in tableting properties with better disintegration and dissolution profile. The bioavailability of the drug would be enhanced due to the increment in these parameters. The results of the stability studies of formulation batch (B2) were satisfactory. This batch with crospovidone as a super disintegrant was selected as the best formulation and recommended for scale-up. Conclusion: The outcome of the research work suggests that the disintegration efficiency of crospovidone is the most among the three super disintegrants and is recommended for the formulation of most effective dispersible tablets of Tramadol Hydrochloride.

Trends in Opioid Prescribing and Dispensing by Veterinarians in Pennsylvania

Veterinarians are a subset of opioid prescribers. To assess the quantity and trends in prescribing and dispensing of several different opioids in the past 11 years in a large veterinary hospital in Philadelphia, Pennsylvania. This cross-sectional study inventoried all opioid tablets and/or patches dispensed or prescribed by veterinarians practicing in a multispecialty academic veterinary teaching hospital in Philadelphia for small animals and species, such as rabbits, birds, and reptiles, from January 1, 2007, through December 31, 2017. Prescribing data were obtained from all veterinarians who wrote a prescription for opioids by reviewing detailed pharmacy records of controlled substances for the study period. Data included all opioids dispensed, or prescribed to animals (patients) undergoing evaluation at the center or being followed up as outpatients by the veterinarians in the hospital. Statewide veterinarian prescribing data were used for comparison. Data were analyzed from December 24, 2017, through May 15, 2018. The trend in administration and prescribing of 4 specific opioid analgesics (codeine sulfate, hydrocodone bitartrate, and tramadol hydrochloride tablets as well as fentanyl citrate patch) during the 11-year study period. The individual opioids were converted to morphine milligram equivalents (MME) for comparison. The study included 134 veterinarians (70.9% women) with 366 468 patient visits. During the study period, the hospital veterinarians prescribed 105 183 689 tablets of tramadol, 97 547 tablets of hydrocodone, 38 939 tablets of codeine, and 3153 fentanyl patches to dogs (73.0%), cats (22.5%), and exotic animals (4.5%). Overall, MME use increased 41.2%, whereas visits increased by 12.8%. The comparison data for Pennsylvania revealed a predominance of hydrocodone use (688 340 tablets prescribed), although data were not available for comparison with tramadol because it is a Schedule IV drug. Results of this study suggest that the large, increasing volume of opioids prescribed at 1 veterinary teaching hospital highlights concerns parallel to those about excessive opioid prescribing in humans. The extent to which these data may represent similar volumes of prescriptions from the general veterinary practices and hospitals across the United States is suggested by the accompanying Pennsylvania state data. These findings highlight an opportunity to assess the risk of veterinarian opioid prescriptions to safeguard public health.

Effect of transcutaneous electrical acupoint stimulation on postoperative analgesia of ureteroscopic holmium laser lithotripsy

To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative analgesia of ureteroscopic holmium laser lithotripsy. One hundred and twenty adult patients, American Association of Anesthesiologists (ASA) Class Ⅰ or Ⅱ, scheduled to ureteroscopic holmium laser lithotripsy, were randomly assigned into an observation group and a control group, 60 cases in each one. The patients in the observation group were treated with TEAS for postoperative analgesia. TEAS was implemented at bilateral Shenshu (BL 23) and Yinlingquan (SP 9) at the time of back ward and postoperative 4 h, 8 h, 12 h. TEAS at 7:00, 11:00 and 15:00 at the above acupoints were used on the second and third days; while placebo (twice a day, 100 mg a time) was used. Tramadol hydrochloride tablets for postoperative analgesia were applied in the contnol group, twice a day, 100 mg a time, and electrode sheets without stimulation were put on Shenshu (BL 23) and Yinlingquan (SP 9). When analgesia was insufficient with the score of visual analogue scale (VAS)≥3, the patients were treated with tramadol tablets for remedy analgesia. The VAS score, the concentrations of serotonin (5-HT) and substance P (SP) in 3 mL venous blood at the time of back ward (T0), postoperative 4 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) were detected respectively. The total amount of medication for remedy analgesia and the incidence of adverse reactions, such as nausea and vomiting within postoperative 48 h were compared between the two groups. The VAS scores at T1 through T4 were lower than those at T0 in the two groups (all P<0.05). Compared with the control group, the VAS scores at T1 through T3 in the observation group were lower (all P<0.05). The total dose of remedy analgesic medicine within 48 h after operation in the observation group was lower than that in the control group (P<0.05). Compared with the control group, the concentrations of 5-HT at T1, T2, T4 and SP at T1 through T4 were lower (all P<0.05). The numbers of constipation, nausea and vomiting in the observation group were less than those in the control group (both P<0.05). TEAS can relieve the pain and reduce the total amount of analgesic medicine, the levels of substance causing pain and the incidence of adverse reactions after ureteroscopic holmium laser lithotripsy.

Effect of transcutaneous electrical acupoint stimulation on postoperative analgesia after ureteroscopic lithotripsy: a randomized controlled trial.

Transcutaneous electrical acupoint stimulation (TEAS) is an effective analgesic measure. We studied the analgesic effect of TEAS by applying it alone after ureteroscopic lithotripsy, rather than applying it as a supplementary analgesic measure. Participants (n = 120) scheduled to undergo ureteroscopic holmium laser lithotripsy, were enrolled and randomly assigned into Group T (TEAS n = 60) and Group C (Control, n = 60). The participants in Group T were treated with TEAS for postoperative analgesia. TEAS were implemented on bilateral Shenyu (BL23) and Yinlingquan (SP9) at the time backward and the time at 4, 8, 12h postoperatively. TEAS was re-implemented three times on the target acupoints for the next 2days. When TEAS failed to meet the analgesic effect, the participants were given tramadol hydrochloride tablets of 100mg. Participants of Group C were given tramadol hydrochloride tablets for postoperative analgesia. The primary outcome of VAS scores at the time backward (T0), 4h (T1), 12h (T2), 24h (T3), 48h (T4) postoperatively and the amount of remedy for analgesic consumption within 48h postoperatively were compared. The secondary outcome of adverse reactions and plasma concentrations of serotonin (5-HT) and substance P (SP) at T0, T1, T2, T3, T4 were detected, respectively. The VAS scores at T1, T2, T3, T4 postoperatively in two groups were lower than T0. Compared to group C, the VAS scores at T1 (3.68 ± 0.68 vs. 4.79 ± 0.82, P = 0.01), T2 (2.64 ± 0.72 vs. 3.92 ± 0.88, P = 0.03), T3 (2.21 ± 0.88 vs. 3.38 ± 0.74, P < 0.01) in Group T were lower, and total remedy of analgesic consumption was significantly lower (127.14 ± 28.46 vs. 415.27 ± 86.37, P < 0.01) within 48h postoperatively. The plasma concentrations of 5-HT in Group T was lower than Group C at T1 (348.54 ± 138.49 vs. 418.69 ± 124.68, P = 0.03), T2 (324.28 ± 112.73 vs. 398.52 ± 114.53, P < 0.01), T4 (309.64 ± 129.09 vs. 388.46 ± 115.36, P = 0.04) postoperatively and concentrations of SP at T1 (59.38 ± 24.68 vs. 78.93 ± 26.32, P < 0.01), T2 (49.36 ± 25.55 vs. 66.49 ± 23.57, P = 0.02), T3 (42.19 ± 24.36 vs. 64.15 ± 28.16, P = 0.04), T4 (39.26 ± 19.88 vs. 54.64 ± 20.62, P = 0.02) postoperatively were also lower than Group C. Meanwhile, the occurrences of vertigo (6.7 vs. 18.3%, P < 0.01), nausea and vomiting (11.7 vs. 21.7%, P < 0.01), constipation (10.0 vs. 20.0%, P = 0.03) in Group T were also lower. Application of TEAS alone was associated with effective alleviation of postoperative pain, reduction of postoperative analgesics consumption, decrease of plasma concentration of algogenic substance and the incidence of adverse reactions after ureteroscopic lithotripsy.

Design and Evaluation of Chronomodulated Drug Delivery of Tramadol Hydrochloride.

Rheumatoid arthritis is an auto immune disease which requires chronotherapy as it occurs during early morning. Tramadol hydrochloride (TH) is an analgesic drug, used to treat rheumatoid arthritis. The aim of the present investigation was to develop chronomodulated drug delivery system of tramadol hydrochloride such that it releases the drug early in the morning, during which the symptoms of rheumatoid arthritis worsen. To develop chronomodulated drug delivery system of TH, initially core tablets of TH were prepared using three different supradisintegrants followed by coating with pH dependent polymer of Eudragit S100. The prepared core tablets are evaluated for physical parameters and an optimal system was identified. Further, coating composition of Eudragit S100 was optimized and coating tablets of TH was prepared. The prepared coated tablets were evaluated for weight variation, hardness, drug content and in vitro release studies in 0.1N HCl, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer. Formulation with 7.5% of coating solution (ES2) had shown a significant drug release after a lag time of 3 h (in pH 6.8 medium), 6 h (in pH 6.8 medium) and 8 h (in pH 7.4 medium), respectively. DSC studies revealed that no interaction between core and coated materials with drug was observed. Thus, chronomodulated drug delivery system of TH was formulated and assuming that if a tablet is administered around 9 pm to 10 pm, the drug release starts after a lag time of 6 h i. e., around 3am to 4 am.

FORMULATION DEVELOPMENT, CHARACTERIZATION AND IN- VITRO EVALUATION OF FLOATING MATRIX DOSAGE FORM OF TRAMADOL HYDROCHLORIDE USING VARIOUS POLYMERS

Objective: The purpose of present study was to formulate the gastro retentive floating tablets of tramadol hydrochloride for enhancement of the gastric residence time.Methods: The floating tablets were prepared by direct compression method and evaluated for hardness, thickness, and friability of the tablets. The in vitro drug release studies were performed for different formulations and to optimize the best formulae based on the dissolution profiles.Results: Fourier transform infrared spectroscopy and differential scanning calorimetry studies revealed that there was no interaction between tramodol hydrocholride and excipients. The formulated tablets were evaluated for properties like weight variation, hardness, thickness, friability, drug content, density and floating properties, matrix integrity and complied with USP requirements. The tablets of optimized formula had floating lag time of 120, 72 and 96 seconds and the tablets remained in the floating condition for more than 12 h. The results of drug excipients compatibility studies suggest that there was no significant change in the physical appearance of these blends, when stored at 40 °C/75% RH for a period of 4 weeks. Among various trial formulations developed with different concentration of polymer F3 (HPMC K4 M with 120mg of polymer), F5 (HPMC K15 M with 100 mg polymer), F11 (PEO WSR 303 with 100mg polymer), were chosen as the optimized formulations based on the release profile.Conclusion: Tramodol HCl floating tablets were successfully made using various polymers for the enhancement of the gastric residence time. From the present study it was concluded that hydroxy propyl methyl cellulose K 4 M can be used as effective polymer for the formulation of floating effervescent tablets of highly soluble drug indicating successful development of sustained release floating drug delivery system.Key words: Tramodol HCl, floating tablets, PEO 303 WSR, PEO N60, HPMC K 4 M, HPMC K15 M and HPMC K 100 M.

Continuous twin screw melt granulation of glyceryl behenate: Development of controlled release tramadol hydrochloride tablets for improved safety

Interest in granulation processes using twin screw extrusion machines is rapidly growing. The primary objectives of this study were to develop a continuous granulation process for direct production of granules using this technique with glyceryl behenate as a binder, evaluate the properties of the resulting granules and develop controlled release tablets containing tramadol HCl. In addition, the granulation mechanism was probed and the polymorphic form of the lipid and drug release rate were evaluated on stability. Granules were prepared using a Leistritz NANO16 twin screw extruder operated without a constricting die. The solid state of the granules were characterized by differential scanning calorimetry and X-ray diffraction. Formulated tablets were studied in 0.1N HCl containing 0–40% ethanol to investigate propensity for alcohol induced dose dumping. The extrusion barrel temperature profile and feed rate were determined to be the primary factors influencing the particle size distribution. Granules were formed by a combination immersion/distribution mechanism, did not require subsequent milling, and were observed to contain desirable polymorphic forms of glyceryl behenate. Drug release from tablets was complete and controlled over 16h and the tablets were determined to be resistant to alcohol induced dose dumping. The drug release rate from the tablets was found to be stable at 40°C and 75% relative humidity for the duration of a 3 month study.

Design and Evaluation of Orally Disintegrating Tramadol Hydrochloride Tablets by Direct Compression Method

Aims: To design and evaluate an orally disintegrating tramadol hydrochloride tablets (ODT). Methods: Tramadol hydrochloride orally disintegrating tablets were designed and manufactured by direct compression method, using Cross povidone, Precirol, EPO, Sorbitol, PEG 6000, Aerosol, HCL, magnesium stearate, xylitol, acesulfame potassium, as key excipients, and peppermint flavor and sweetener, respectively. These formulations were then evaluated using pharmacopoeial and non-pharmacopoeial physical and chemical tests. Dissolution and assay tests were performed using USP apparatus II and ultraviolet (UV) spectrophotometry, respectively. Results: The tablet formulation prepared with crospovidone (F1) showed good flow properties, low disintegration time (13 s) and improved drug release (100% at 30 min) compared with those of the other formulations (84 % at 30 min). All the formulations exhibited satisfactory physicochemical characteristics. The results indicated that suitable ODT of tramadol could be prepared. Conclusion: A suitable preparation of tramadol Hcl ODT which contains Crospovidone (superdisintegrant) and sorbitol (bulking agent) was found to be the best among Tramadol hydrochloride ODT formulations prepared by direct compression method, because it has exhibited good disintegration time and good dissolution profile when compared to other formulations.

Formulation and Evaluation of Mouth Dissolving Tablets of Tramadol Hydrochloride

Purpose: To prepare, and evaluate in vitro and in vivo tramadol hydrochloride mouth dissolving tablets (MDT).Methods: Tramadol HCl MDT were prepared by direct compression using Pharmaburst as coprocessed excipient and compared with a reference product (Rybix ODT, 50 mg). Physicochemical parameters including hardness, friability, weight variation, disintegration time and dissolution studies were determined for all the formulations. In-vivo studies were performed for the optimized formulation (F13), using as reference, a commercial product (Trambax IR, 50 mg), by a two-way crossover design under fasting conditions on eight healthy adult human subjects. Drug-plasma concentrations obtained from the bioequivalence study for test and reference products were analyzed in each subject by high performance liquid chromatography (HPLC), and basic pharmacokinetic parameters, including Cmax, Tmax, AUC0-t, AUC0-∞, t½ and λz, were calculated.Results: The tablet formulation prepared with Pharmaburst (F13) showed good flow properties, low disintegration time (15 s) and improved drug release (99 % at 30 min) compared with those of the reference product (88 % at 30 min) and passed 6 months accelerated stability test. Bioequivalence of the test product with that of the reference product under fasting conditions was established by computing 90 % confidence interval for the In-transformed pharmacokinetic parameters of Cmax, AUC0-t and AUC0-∞ for tramadol. The 90 % confidence intervals for Cmax were 99.70 - 114.31, for AUC0-t 97.31 - 108.87 and for AUC0-∞ 97.17 - 109.75. This confidence interval, in each case, was within bioequivalence criteria limitConclusion: A suitable preparation of tramadol HCl MDT that is bioequivalent with a reference commercial product under fasting condition can be obtained when Pharmaburst is used as a disintegrant.Keywords: Bioequivalence, dissolution, Mouth dissolving tablets, Pharmaburst, Tramadol hydrochloride, Disintegration time

A randomized trial to compare pain control using oral analgesia with epidural analgesia after cesarean section following combined spinal-epidural anesthesia

This study aimed to evaluate whether combined oral oxycodone hydrochloride-controlled release tablets plus paracetamol and tramadol hydrochloride tablets are more effective than epidural analgesia for postoperative pain control and side effects after cesarean section. We randomly enrolled 60 patients scheduled for cesarean section into either: patient-controlled epidural analgesia with 0.1% ropivacaine+0.1 μg/mL sufentanil (for postoperative 48 h)+injected pethidine on demand (E group); or controlled-release oxycodone (2x15 mg for the first postoperative 24 h; 2x10 mg for the second postoperative 24 h)+paracetamol and tramadol hydrochloride tablets (8x1 tablet for the postoperative 48 h) orally+injected pethidine on demand (O group). The E group experienced more evoked pain and uterine cramping pain at all times postoperatively. The patients who received oral analgesia had less resting pain at 6, 12, 24, and 36 h after surgery. Two patients in the E group injected pethidine (150 mg total) during the oxytocin infusion, whereas none of the O group patients injected pethidine. Pruritus was more common in the E group (P<0.05). Maternal satisfaction with the analgesia regimen was lower in the E group (P<0.01). The median duration of hospital stay was about 5 days for both groups. Postoperative pain control after cesarean section with oral oxycodone hydrochloride-controlled release tablets plus paracetamol and tramadol hydrochloride tablets is preferable to epidural analgesia, even when side effects and maternal satisfaction are taken into account.

Study on Sustained-Release Tablets of Tramadol Hydrochloride

Study on Sustained-Release Tablets of Tramadol Hydrochloride

Formulation and evaluation of bilayer sustained release tablets of tramadol hydrochloride by using natural and synthetic polymers

The main objective of the present work was to develop sustained release bilayer tablets ofwater soluble drug tramadol using Guargum, HPMC, NaCMC and Xanthan gum, either alone or in combinations. Tablets were prepared by immediate release direct compression and sustained release wet granulation method and evaluated for various physical parameters. The drug release studies were performed using USP apparatus type І using 0.1N Hcl and pH 6.8 phosphate buffer as dissolution medium. The drug release was dependent on the type and concentration of the polymer. Drug release was faster from tablets prepared with Guargum, NaCMC and HPMC alone. However, in combination with HPMC, NaCMC, Guargum with Xanthan gum it sustained drug release effectively. The rate and mechanism of release of Tramadol Hcl analysed by fitting the dissolution data into the zero order, First order, Higuchi, Korsmeyer-Peppas and hexon crowel equations. All the Formulations (F1-F10) followed Zero order release Mechanism. Higuchi plots for all the formulations were linear indicating the drug release by diffusion controlled. Hixon-Crowell cube root model showed high r2 value proportionality due to erosion of hydrophilic gel layer. To explore the release pattern, results of the in-vitro dissolution data were fitted to the Korsmeyer-Peppas equation, which characterizes the transport mechanism indicates the non fickian transport it refer to combination of both diffusion and erosion rate release. It can be concluded that the optimized batch F7 by adopting biphasic drug release pattern in a single dosage could improve patient compliance and give better disease management.

Formulation and Evaluation of Bi-layered SustainedRelease Matrix Tablets of Tramadol Hydrochloride

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique incorporating an immediate release layer and a sustained release layer. An immediate release layer was successfully designed to release the bolus dose instantaneously. Water soluble Xanthan gum, water insoluble Kollidon SR and Eudragit L 100 were used as carriers in the sustained release layer of the matrix tablet. All the tablets were evaluated for thickness, diameter, weight variation, hardness and friability. The in vitro drug release was studied for eight hour, first two hours dissolution in acidic medium followed by six hour dissolution in buffer medium. Matrix tablet showed a sustained release rate with a controlled fashion as a function of the quantity of polymer used. The in vitro drug release data were fitted with several mathematical models and mean dissolution time along with fractional dissolution time values (T25%, T50% and T80%) were calculated. Xanthan gum was found to be the most effective rate retarding agent compared to Kollidon SR and Eudragit L 100, when used at same ratio in the formulations.

Oral controlled-release oxycodone for uterine cramping pain after cesarean section

To evaluate whether combined oral oxycodone hydrochloride controlled-release tablets plus paracetamol and tramadol hydrochloride tablets is better than epidural analgesia with respect to uterine cramping pain control and side effects after cesarean section. Sixty consecutive patients scheduled for cesarean section from April to May, 2010 were randomized to either patient-controlled epidural analgesia with 0.1% ropivacaine, 0.1 µg/ml sufentanil (for postoperative 48 h) plus injected pethidine on demand (EDA group) or controlled-release oxycodone (2 × 15 mg for 1st postoperative 24 h; 2 × 10 mg for 2nd postoperative 24 h), paracetamol & tramadol hydrochloride tablets (8 × 1 tablet for postoperative 48 h) orally plus pethidine injection on demand (OXY group). Two groups were compared with respects to uterine cramping pain control when the oxytocin infusion (20 U plus 500 ml 5% glucose solution, iv. gtt within 2 h) once per day for postoperative 3 days as determined by the means of a visual analogue scale (VAS), pethidine consumption, side effects and costs. The EDA group experienced significant more pain than the OXY group when the oxytocin infusion was administered (mm) [50.0 (15.0, 72.5) vs 25.0 (0, 40.0), 60.0 (47.5, 72.5) vs 20.0 (0, 30.0), 35.0 (20.0, 50.0) vs 0 (0, 20.0)]. all P < 0.05). Pethidine was used for pain control in 2 patients (150 mg total) of EDA group during the oxytocin infusion whereas none of the OXY group received an injection of pethidine. There was a higher level of maternal satisfaction with a lower analgesic dose in the EDA group (80.9 ± 9.3 vs 90.0 ± 9.8, P < 0.01). The median duration of hospital stay was around 5 days in both groups. Postoperative pain control after cesarean section with the above combined regimen is superior to EDA in terms of a lower cost and a higher level of maternal satisfaction.

Preparation and Evaluation of Sustained Release Matrix Tablets of Tramadol Hydrochloride Using Glyceryl Palmitostearate

Purpose: To prepare oral sustained release matrix tablets of a highly water soluble drug, tramadol hydrochloride, and to evaluate the effect of concentration of the hydrophobic polymer content and method of preparation on drug release. Methods: The tablets were a mixture of both tramadol hydrochloride and glyceryl palmitostearate (GP) prepared by melt granulation (MG1, MG2, MG3 and MG4 in ratios 1:1, 1:2, 1:3 and 1:4, respectively) or by direct compression (DC, 1:2 ratio). The hardness of the tablets was measured. Drug/GP interaction was determined by FT-IR spectroscopy while drug release from the matrix tablets was studied using USP II dissolution apparatus. The release data were subjected to different models in order to evaluate their release kinetics and mechanisms. Results: The hardness of the tablets was in the range of 5.30 ± 0.36 - 6.50 ± 0.10 kg/cm2. FT-IR spectra showed that there was no clear interaction between the drug and the glyceride. Of the formulations (MG1 to MG4) prepared by melt granulation, MG4 showed the most suitable sustained release, 58.4 ± 1.1 % in 12 h (p Keywords: Tramadol hydrochloride; Glyceryl palmitostearate; Melt granulation; Direct compression; Sustained release.

Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of −0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables.

Formulation design and optimization of taste-masked mouth-dissolving tablets of Tramadol hydrochloride

Formulation design and optimization of taste-masked mouth-dissolving tablets of Tramadol hydrochloride

Formulation design and optimization of tastemasked mouth-dissolving tablets of Tramadol hydrochloride

The aim of the present study was to mask the extremely bitter taste of Tramadol HCL, an opioid analgesic, and to formulate a tablet which can rapidly disintegrate in saliva (rapidly disintegrating tablet). The crucial aspect in the formulation of mouth-dissolving tablets is to mask the bitter taste and to minimize the disintegration time. Taste masking was done using sweetening agent and D-mannitol and taste-masked pellets were prepared by extrusion spheronization technique. Prepared pellets were tested for drug content, taste evaluation in oral cavity and molecular property. Pellet shows significant taste masking, confirmed by in vitro taste evaluation; therefore, it was selected for further study. Pellets were evaluated for density, angle of repose, Carr’s index, Hausner’s ratio and sphericity while tablets were evaluated for disintegration and in vitro dissolution. A 32 full factorial design and statistical models were applied to optimize the effect of two factors, i.e. superdisintegrant sodium starch glycolate and taste-masking agent (D-mannitol). In this study, response surface methodology was used for designing of the experiment, generation of mathematical models and optimization study. Taste evaluation of pellets in human volunteers revealed considerable taste masking with a degree of bitterness below threshold value (2.0) within 10 s, whereas Tramadol HCl was rated intensely bitter with a score of +4 for 10 s. The size of the pellets varied from 0.895 to 1.423 mm for different batch and found to be a spherical. Disintegration time of different formulations varied from 30 to 60 s. It was observed that the responses, i.e. disintegration time and sphericity were affected by both the factors. The statistical models were validated and can be successfully used to prepare optimized taste-masked mouth-dissolving tablets of Tramadol HCl with adequate disintegration and shape. Key words: 32 factorial design, rapidly disintegrating tablet, response surface methodology, taste-masked granule, Tramadol HCL

Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers

By using a high-performance liquid chromatography method, the pharmacokinetics of the tramadol (T) and its three main metabolites, O-desmethyltramadol (M1), N-desmethyltramadol (M2) and O,N-didesmethyltramadol (M5) was studied in healthy male and female Iranian volunteers after oral administration of two 50 mg tramadol hydrochloride tablets. The related pharmacokinetic parameters such as C(max), T(max), AUC((0-t)), AUC((0-infinity)), T(1/2) and Cl/F were calculated and compared between the two genders. No significant differences were found in the systemic exposure and pharmacokinetic of tramadol, M1 and M2 while there were significant differences in AUCs of M5 in the two genders. It was concluded that to get a more accurate result, the gender dependency of T and its metabolites might be studied in specific phenotypes.