The tramadolhydrochloride-resin complexes were prepared by a batch processes. For the batch method, the previously purified indion 254 resin particles (100 mg of dry weight resin) were dispersed in a 2 % (w/v) drug solution (50 ml) under magnetic stirring at room temperature for 2 h. After carefully decanting the clear supernatant of the above, another 50 ml of fresh drug solution was added and stirred again for 2 h at room temperature; this procedure is an alternative method called as modified batch method. 0.1ml of supernatant was collected at fixed intervals during complex formation at room temperature, diluted with water, and then the drug amount was quantified by UV spectrophotometer (Shimadzu 1600) at 271 nm. The drug–resinate beads were separated from the supernatant by filtration, washed with deionized water to remove any non-complexed drug, and then dried in an oven at 40°C for 24 h and then stored in tightly closed desiccators. Standard calibration curves were prepared before analysis to monitor the linearity from 10 to 100 µg /ml at 271 nm.
A simple, precise, accurate and reproducible spectrophotometric method has been developed for simultaneous estimation of Tramadolhydrochloride (TRA) and Diclofenac Sodium (DIC) by employing first order derivative method by using methanol as solvent. The first order derivative absorption at 251.13 nm (zero cross point of Diclofenac sodium) was used for quantification of Tramadolhydrochloride and 273.75 nm (zero cross point of Tramadol) for quantification of Diclofenac sodium. The linearity was established over the concentration range of 5- 25 µg/ml in and 5-45µg/ml for Tramadol and Diclofenac sodium respectively. The correlation coefficient (R 2 ) for Tramadol 0.9998 and for Diclofenac sodium 0.9991 .The mean % recovery was found to be in range of 99.00% and 99.68% for TRA and DIC, respectively. The proposed method fulfils the validation parameter as per ICH guidelines and was successfully applied to the estimation of TRA and DIC in bulk as well as in synthetic mixture.
Tramadol was procured as a gift sample from Research Centre in Vadodadara. All the other chemicals were purchased from Sigma Aldrich and TCI Chemicals. DSC instrument was Make of Metler Toledo at KLE University College of Pharmacy Belagavi. The Tramadolhydrochloride was dissolved in different solvents like 1, 4 – dioxan, chloroform, diethyl ether to from the polymorphs.
Sustained release provides the most desirable dosing regimens with effective pharmacokinetic profile and pharmacodynamic response. This is potentially useful to overcome problems associated with conventional dose and has advantage of patient compliance. In present investigation, the study was aimed to formulate and in- vitro evaluation of sustained release tablets of Tramadolhydrochloride using polymeric matrix system. The matrix system adopted in this study had Hydroxy Propyl Methyl Cellulose K100M and Ethyl cellulose as rate retarding polymers individually as well as in combinations and in varying concentration of polymers in order to investigate the effect on drug release. Matrix tablets of Tramadol HCl were prepared by direct compression method. Various formulation with different concentration of polymers were tried to optimize the process and release of the drug. The pre-compression parameters were characterized for flow properties, compressibility index and other physical proprieties. The prepared tablets were evaluated for different parameter such as weight variation, diameter, hardness, friability, disintegration, swelling index and drug content. The in-vitro drug release profiles were studied in two media (0.1N HCl and Phosphate buffer pH 6.8). All the tablets prepared possess a weight variation below ±5%, hardness of (6.77 to 8.05) kg/cm 2 , percentage friability of (0.33 to 0.94%), diameter (10.10 to 10.19 mm. The drug content was in between 98.01% to 105.74%. Among all the formulations, sustained release tablets (F7) were considered to be the successful formulation which showed drug release upto 95.32%, and showed very close to release profile of the marketed sample which suggests the release the mechanism of drug from diffusion coupled with erosion. Increased concentration of polymers revealed the decreased release rate due to increase in diffusional path length and decreased
chemical name for tramadolhydrochloride is (±)cis – 2 - [ ( dimethylamino ) methyl ] – 1 - ( 3methoxyphenyl ) cyclohexanol hydrochloride. Tramadolhydrochloride was first introduced into clinical practice in the last seventies as a strong analgesic of opioid profile acting on receptors. Tramadolhydrochloride has been proved to be effective in both experimental and clinical pain without causing serious cardiovascular or respiratory side effects 6 . The half-life of the
To interpret the pharmacokinetics and pharmacodynamics properties of a drug molecule, plasma protein binding plays a substantial factor. The present study has been done to investigate the interaction of Tramadolhydrochloride (TRD) with bovine serum albumin (BSA) under physiological condition (pH 7.40) using UV absorption and fluorescence spectrophotometry at different temperatures (298K and 308K). Spectral methods are the most robust tech
and mixed using geometric dilution method to improve the drug distribution and content uniformity and then triturated well in a mortar. Wet granulation, was carried out with moisture activation. The final mass was passed through sieve #20 and the granules thus obtained, were dried in hot air oven at 60°C for 15-20 min. The granules were then passed through sieve #30 and collected in suitable container. Then magnesium stearate, talc, aspartame, MCC- pH 102, superdisintigrant, flavour were passed through sieve #80, mixed and blended well with the initial mixture. The mixed blend of the drug and the excipients was compressed using REMEK 10 station rotary punching machine to produce tablet weighing 200 mg having a diameter of 8 mm. Following the procedure, ten batches of orodispersible tablets of Tramadolhydrochloride in different ratios of superdisintegrants were prepared.
A simple, accurate and sensitive reversed-phase HPLC method for the simultaneous quantification of paracetamol and tramadolhydrochloride in fixed-dose combination tablets have been developed and validated per the International Conference on Harmonization guidelines. The method was also used to study the stability profile of paracetamol and tramadolhydrochloride under stress conditions. The newly developed method is easy to operate, requires a relatively shorter analysis time and is stability-indicating (it can be used to study the stability profile of paracetamol and tramadolhydrochloride). This new method can therefore be used for the routine analysis of fixed-dose combination
The American Academy of Paediatrics and American college of Obstetricians and Gynaecology (2007) have specified that it is the responsibility of the obstetrician or certified midwife in consultation with an anaesthesiologist to formulate pain relief . In the present study, 400 patients were studied. Study group: 200 patients in active labour who received 100mg tramadolhydrochloride Control group:200 patients in active labour who did not receive the drug.
Epidural narcotics have been extensively used for post-operative analgesia. 4 With discovery of newer opioids like Butorphanol tartrate , Tramadolhydrochloride and fentanyl citrate, a new era in pain relief has commenced. Butorphanol tartrate , a synthetic opioid derivative is a mixed agonist and antagonist non-narcotic opioid analgesic where as Tramadolhydrochloride is a synthetic 4-phenyl-piperdine analog of codeine with a dual mechanism of action. The advantage with these newer drugs is that their potency is comparable to that of morphine, produce lesser respiratory depression, easily available, larger margin of safety and lesser incidence of nausea, vomiting, urinary retention, pruritus compared to morphine. 5,6 Hence it is feasible to conduct the present study to assess the safety and efficacy of post- operative analgesia with epidural Butorphanol tartrate compared with epidural Tramadolhydrochloride.
The objective of this study was to formulate and optimize taste masked rapidly disintegrating tablet of intensely bitter drug tramadolhydrochloride by 3 factorial design. The drug polymer complex was prepared by coacervation method using aminoalkyl methacrylate copolymer (Eudragit EPO) as polymer and sodium hydroxide as precipitant and characterized for molecular properties, drug content, in vitro dissolution and taste evaluation. Drug polymer complex with a ratio of 1:8 was selected based on no release in phosphate buffer pH 6.8 showing successful taste masking of drug. Bitterness score was evaluated by human gustatory sensation test. The bitterness score of drug polymer complex was decreased as compared to tramadolhydrochloride. Optimized drug polymer complex was
Mouth dissolving tablet is a novel dosage form, have several characteristics to distinguish them from the more traditional dosage form. The purpose of this research was to prepare mouth dissolving tablet of tramadolhydrochloride by sublimation method with a view to enhance patient compliance. Tramadolhydrochloride is a centrally acting analgesic, which is orally and intravenously administered drug. The sublimating agent used in this study was camphor & ammonium bicarbonate, The prepared batches of tablets were evaluated for uniformity of weight, thickness, hardness, friability, wetting time, water absorption ratio, disintegration time and dissolution study. Amongst all formulations, formulation F3 prepared by 5% crosscaramellose sodium & 15% camphor showed least disintegrating time and faster dissolution.
In vitro dissolution study was carried out in triplicate for resinates equivalent to 100 mg of tramadolhydrochloride placed into 900 ml of Dissolution medium, by using the USP paddle apparatus (Electrolab TDT 06L). Speed of paddle rotation was fixed at 50 rpm and temperature maintained at 37 ± 0.5°C. At predetermined intervals 5 ml aliquots were withdrawn and replaced with the same volume of fresh dissolution medium. The collected aliquots were filtered through whatman filter paper no.41 and amount of drug released was analyzed by UV-vis spectrophotometer at 271 nm following suitable dilutions.
Paracetamol (PCM) is thought to act primarily in the CNS, increasing the pain threshshold by inhibiting both isoforms of cyclooxygenase, COX-1 and COX-2, enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDS, Paracetmol does not inhibit cyclooxygenase in peripheral tissues and thus has no peripheral anti-inflammatory effects. Paracetmol indirectly blocks COX, and that this blockade is ineffective in the presence of perioxides. The drug selectively blocks a variant of the COX enzyme that is different from the known variant COX-1 and COX-2. Literature review reveals that simultaneous determination of PCM and TH content in tablets can be achieved by spectrophotometry, [3-9] high performance thin layer chromatography [10-13] and reverse phase high performance liquid chromatography [14-18]. Among the different analytical equipments and techniques, Reverse Phase High Performance Liquid Chromatography (RP-HPLC) stands out due to its resolution, specificity, accuracy, precision and cost effectiveness. The mobile phase used in the HPLC methods mentioned above is a mixture of either methanol or acetonitrile along with buffer. The important disadvantages of using methanol are the requirement of poison license to purchase it, higher noise at lower ultraviolet wavelengths (lesser than 250 nm), and higher column pressures. The use of buffer causes salt deposition effect on HPLC parts and frequent washings are required after its use. The advantages of using acetonitrile include greater sensitivity for analysis at shorter wavelengths, greater elution strength, and less ghost peaking during gradient technique. Another advantage of the present method is that it avoids the use of triethylamine which can alter the column in a way that is not easily reversible and retention time for paracetamol and tramadolhydrochloride was found less in which the consumption of moile phase is less. The present study describes the development and validation of an optimal isocratic RP-HPLC method for simultaneous quantitative estimation of PCM and TRD in tablet formulation .
The Drug Loading Efficiency of Implants: The loading dose has a significant effect on resulting release kinetics along with drug solubility. In case of freely water-soluble drugs, the porosity of matrix upon drug depletion increases with increasing initial drug loading. This effect leads to increased absolute drug transfer rate. The loading efficiency of the implant is dependent on several factors related to the drug, polymer, and solvent properties. Implants were analyzed for actual TramadolHydrochloride content against theoretical drug content. The percentage of loading efficiency (%LE) of implants was determined with the formula:
Injectable agents are very common for induction and/ or maintenance of general anesthesia in cats. Alpha2 (α2) adrenoceptor agonist- ketamine combination is one of the most common injectable anesthetic protocols for achieving general anesthesia in cats (Neven, 2013). Xylazine hydrochloride is an α2 adrenoreceptor agonist widely used in cats for its sedative, analgesic and muscle relaxant effects (Pypendop, 2005). Xylazine combined with Ketamine to increase its anesthetic and analgesic effects and to reduce the dose required to induce satisfactory anesthesia. However, its use is associated with adverse effects including bradycardia and respiratory depression (Lemke, 2004; Pypendop, 2005). Ketamine hydrochloride is a dissociative anesthetic with central sympathomimetic activity when used alone it tends to poor muscle relaxation and persistent pain reflex. The muscle twitching and rigidity and convulsive seizures are centrally mediated. Ketamine produces a dose dependent depression of cardiac function (Pratila and Pratila, 1978). Tramadolhydrochloride is a centrally acting analgesic that is structurally related to codeine and morphine (Shilo et al. 2008). It acts as a weak m-opioid agonist coupled with inhibition of synaptic reuptake of serotonin and norepinephrine, achieving spinal modulation of pain and preventing impulses reaching the brain (Kongara et al. 2009). It had been used in several species, including cats (De Sousa et al. 2008; Paulo; Steagall, 2008). It was hypothesized that tramadol in combination with XK will provide extra depth and duration of analgesia than XK alone. The aim of this study was to Judge the effect of adding tramadol HCL in a dose of 2mg/kg to xylazine ketamine combination and to evaluate XKT combination analgesic effect and its effect on depth and duration of anesthesia.
Tramadolhydrochloride, a centrally acting oral analgesic, has high solubility and bioavailability in the biological fluids and thus possesses a major drawback of adverse effects (since it reaches a high concentration in the central nervous system in a shorter period of time). So, to reduce the limitations of the drug on oral and parenteral administration (which are the only drug delivery systems available currently), development of topical formulation of Tramadolhydrochloride was considered.
In latest years, genotoxic impurities have become a subject of increasing interest in pharmaceutical industries. Several reports on regulatory and toxicology evaluation, control approach and risk assessment have been published [10-14]. Therefore, effective analytical techniques are needed for selective, sensitive and robust detection and quantification of genotoxic impurities at low level. Most nations have their own specific rules and guidelines for genotoxicity testing of pharmaceuticals. Mutagenicity and carcinogenicity tests are needed if the substance or its metabolite is structurally linked to a recognized carcinogen or if the drug‘s nature and action suggests a carcinogenic or mutagenic potential . Most of the pharmaceutical substances are available as HCl salts (Eg: Ondansetron HCl, Doxapram HCl, Dobutamine Hcl, Tramadol HCl etc.). As part of the manufacturing of these acidic salts, active pharma ingredient manufacturers use lower alcohols (Eg: methanol, ethanol, 2-chloropropanol) for purification and salt formation. As part of this process there is a possibility of generation of alkyl halides like methyl chloride, ethyl chloride and 2-chloropropane [16-18]. Tramadolhydrochloride is a codeine synthetic analogue with analgesic properties. Tramadolhydrochloride acts as agonist for receptors of delta-opioid, kappa-opioid, mu-opioid receptor agonist [19, 20]. Tramadolhydrochloride is used for the therapy of mild-to-moderate pain. Tramadol was chemically described as (1R,2R)-2-[(dimethylamino)methyl]-1-(3- methoxyphenyl) cyclohexan-1-ol;hydron;chloride (Fig. 1A). 2- Chloropropanol is used during the manufacturing of tramadol HCl. There is a possibility for the presence of 2- chloropropane in the final drug substance as residual impurity. 2-Chloropropane (Fig.1B) comes under potential carcinogenic impurity as per its structure as primary alkyl halides (Fig. 1C).
The two different brands (CONTIN – SR and TRAMAZAC – TC) were purchased from different medical store in trichy, Tamilnadu. The all tablets of CON were labelled to contain 100mg of Tramadolhydrochloride per tablet and has shelf life of one year. The TC were labelled to contain 100mg per tablet and has a shelf life of 3 years. 20 tablets of two different brands T.HCL(CONTIN – SR,TRAMAZAC –TC) from the marketed sample were weighed and crushed uniformly with the help of mortar and pestle. By calculating the average weighed sample powder equivalent to 20 mg of T.HCL was transferred into a volumetric flask containing 10 ml water. The solutions were sonicated for about 5 to 7 minutes and then filtered with the help of Whatmann No 1 filter paper. The first 5 ml of filtrate was discarded. The remaining amounts of filtrate of both solutions were made up volume up to 100ml with water.
Tramadolhydrochloride is a mild, non-addictive, centrally acting binary analgesic agent, during the process development of Tramadolhydrochloride, four related substances (Impurities) were observed along with the final API.Those impurities were identified as,[2-(3-methoxyphenyl) cyclohex-1-enyl]-N,N-dimethylmethanamine hydrochloride(6),(1RS)-[2-(3-methoxyphenyl)cyclohex-2-enyl]-N,N-dimethylmethanaminehydrochloride(7),(3- ((1R,2R)-2-((dimethylamino)methyl)-1-hydroxyclohexyl)phenol hydrochloride(9) and 3,3'-Dimethoxy-biphenyl(11). Present work describes the synthesis and characterization of all these four impurities.