Tenoxicam Research Articles

The effect of β-cyclodextrin on tenoxicam photostability, studied by a new liquid chromatography method; the dependence on drug dimerisation

Tenoxicam (TXM) is an effective anti-inflammatory and analgesic drug, which presents fast photochemical decomposition. In this work in an attempt to investigate the potential β-CD photostabilizing effect on TXM, the photodegradation rate of β-CD complexed drug was monitored under simulated solar irradiation from Xenon arc lamp. The photodegradation was studied at pH 7.5. A new stability indicating Liquid Chromatography method, for TXM in the presence of β-CD was used. According to the obtained results, in the case of free molecules increasing the concentration the photostability is enhanced. The effect of complexation with CDs on the photodegradation rate seems to vary depending on TXM initial concentration. At low TXM concentrations photodecomposition is retarded upon CD complexation, while at high concentrations the process is accelerated. Molecular dimerisation was studied by 1H(1D) NMR and 2D NOESY experiments. 2D ROESY spectra of complexed molecule were evaluated in order to confirm the complexation. TXM dimers could be considered as a critical parameter affecting oxicams photostability, in combination with the already described ESIPT phenomenon.

Indirect Flow-Injection Spectrophotometric Determination of Meloxicam, Tenoxicam and Piroxicam in Pharmaceutical Formulations

A simple and sensitive indirect spectrophotometric method for the assay of meloxicam (MX), tenoxicam (TX) and piroxicam (PX) in pure and in pharmaceutical formulations by flow injection analysis (FIA) has been proposed. The method is based on the oxidation of these drugs by a known excess of N-bromosuccinimide (NBS) in an acidic medium, followed by a reaction of excess oxidant with chloranilic acid (CAA) to bleach its purple color. The absorbance values increased linearly with increasing concentrations of the drugs. Variables, such as the acidity, reagent concentrations, flow rate of reagents and other FI parameters were optimized to produce the most sensitive and reproducible results. The system obeyed Beer's low over concentration ranges of 10 - 160, 20 - 200 and 10 - 160 microg/ml for MX, TX and PX, respectively. The common excipients and additives did not interfere with their determinations. The method was successfully applied to the determinations of MX, TX and PX in various pharmaceutical preparations. The results obtained by the proposed method were found to be in good agreement with those found by the official HPLC methods.

Formulation and evaluation of tenoxicam gels for tropical use

No Abstract. The East and Central African Journal of Pharmaceutical Sciences Vol. 8(1) 2005: 14-19

Perioperative tenoxicam well tolerated

Perioperative tenoxicam well tolerated

Ratio Derivative S~ectrophotometricM ethod for the Determination of Some Oxicams in Presence of their Alkaline Dearadation Products

A new spectrophotometric method has been developed for the determination of some oxicams namely, lornoxicam (LX) , tenoxicam (TX) and meloxicam (MX), in the presence of their main alkaline degradation products, 2-aminopyridine ( I ) and 2-amino-5-methylthiazole (II) for (TX&MX), 2-aminopyridine and TX for lornoxicam. The method is based on the use of the first derivative of the ratio spectra (1DD) of the mentioned compounds and their corresponding degradates. The procedure does not require any separation steps. Linear calibration graphs of 1DD were obtained by measurement of the amplitudes at 316, 249 and 260nm for LX, 248.8 , 258.8 nm for TX and 287.2nm for MX. On carrying out measurements at the above mentioned wavelengths, the linearity range is found to be 2.5 - 35 μg ml-1 for LX and TX, 1.25 - 30 μg ml-1 for MX. The validity of the method was assessed by applying the standard addition technique. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The suggested procedure could be used for the determination of the above mentioned drugs in pure and dosage forms as well as in presence of their degradation products.

Spectrofluorimetric determination of 2-aminopyridine as a potential impurity in piroxicam and tenoxicam within the pharmacopoeial limit

The British Pharmacopoeia defines 2-aminopyridine (2-AP) as a potential impurity in piroxicam (PX) and tenoxicam (TX). Selective spectrofluorimetric determination of 2-AP in PX and TX, within or near the pharmacopoeial level, 0.2%, was developed, based on the measurement of the native fluorescence either in aqueous 0.1N sulfuric acid or in dioxane. Accordingly, this approach was followed for confirming purity of PX and TX in bulk and pharmaceutical preparations. The study was also extended to include simultaneous determinations of PX/2-AP and TX/2-AP systems based on selective fluorescence measurements in the cited solvents.

Study of the Complexation Behavior of Tenoxicam with Cyclodextrins in Solution: Improved Solubility and Percutaneous Permeability

ABSTRACTComplexation of tenoxicam (TEN) with γ-, HPγ-, β-, HPβ-, and Mβ-cyclodextrin (CD) in aqueous solution at pH 7.4 has been investigated using phase solubility diagrams. TEN formed soluble complexes with 1:1 stoichiometry with all the CDs studied, although the inclusion stability constants (K1:1) obtained had low values. The presence of propylene glycol (PG) in the dissolution medium decreased the stability constants and led to a higher fraction of free drug by competitive displacement and by an increase in the lipophility of the media.Among the CDs tested, MβCD was chosen for further studies since TEN–MβCD complexes yielded the best results: good solubility and the highest stability constant. The effect of MβCD and PG on the TEN partitioning coefficient was also studied in skin–buffer systems. Although each substance reduced the partitioning value, the combination of PG and MβCD increased this parameter.The noticeable increase in solubility of the drug found in the presence of MβCD allowed the formulation of carbopol gels with higher doses of TEN and a reduced amount of cosolvent. The presence of MβCD improved the percutaneous penetration of TEN through abdominal rat skin by increasing the solubility of the drug in the vehicle and by affecting the partitioning behavior of TEN in the skin. In addition, TEN retention in the skin was found to be related to the flux values attained with the corresponding gels.

Combined effect of oleic acid and propylene glycol on the percutaneous penetration of tenoxicam and its retention in the skin

The influence of oleic acid (OA) on the in vitro percutaneous absorption of tenoxicam (TEN) and its combined effect with propylene glycol (PG) was studied using Franz-type diffusion cells. Furthermore, at defined concentrations of OA, complexes of the drug with cyclodextrins (MβCD and γCD) were added because their combined use may be an interesting approach to raise TEN flux. In addition, the amount of TEN retained in the skin after topical administration of several formulations was determined. It was found that OA content markedly increased TEN absorption when compared to the control gel; the highest drug flux was obtained by 15% of OA. The absorption rate of TEN increased in parallel with increasing OA concentration, due to the alteration of the stratum corneum caused by this enhancer. Moreover, the action of OA is likely to be strongly dependent on the vehicle used since drug penetration tended to increase with increasing PG content in the vehicle, especially at the high OA concentrations. Contrary to our expectations, addition of CD complexes did not produce a significant further enhancement. Skin pretreatment with OA, independently of the vehicle used to dissolve the fatty acid, dramatically improved TEN percutaneous penetration. The amount of TEN retained in the skin was related to the flux values obtained with each formulation.

Interaction of Tenoxicam with Cyclodextrins and Its Influence on the In Vitro Percutaneous Penetration of the Drug

Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar ratio, were obtained by the coprecipitation method and characterized by x-ray diffractometry, infrared spectroscopy, and differential scanning calorimetry. The binding capacity of the CDs with TEN was also demonstrated in aqueous solution and in water-propylene glycol mixtures. The purpose of this study was to determine the effect of CDs on the in vitro percutaneous penetration of TEN from carbopol gels, taking into account the role of the CD cavity size and the nature of the substituents. The effect of pretreatment was studied too. In vitro permeation experiments were carried out on Franz diffusion cells using cellulose nitrate membranes and abdominal rat skin. In these results, the release rates of the drug scarcely decreased when the CDs were added, probably because of a lower concentration of the free drug and an increased gel viscosity. However, it was also found that CDs, particularly γ-CD and M-β-CD, can improve slightly TEN absorption through the skin. Pretreatment studies with CDs, however, provided no effects on TEN permeation, but lag time was markedly reduced, suggesting a faster partitioning of TEN into the skin. Therefore, the use of pretreatment with CDs would be interesting when a quick action of the drug is desired.

Flow-injection spectrophotometric methods for the determination of tenoxicam

Two sensitive and rapid flow-injection spectrophotometric methods are proposed for the determination of tenoxicam (TX). In the first method, a Fe(III)–tenoxicam complex is formed in a methanolic medium and the absorbance is measured at 540 nm, while the second method involves measurement of the absorbance at 355 nm of a solution containing the drug in hydrochloric acid medium. In both methods, the peak heights were proportional to tenoxicam concentration over the ranges 7.0–320 and 0.5–8.5 mg l −1, respectively. The methods have been applied to the routine determination of the drug in dosage forms.

Quantitative Determination of Tenoxicam by Infrared Spectrophotometry

The purpose of this study was the quantitative determination of solid dosage forms containing tenoxicam (TNX) by IR spectrophotometry, using the KBr disc technique. Dehydrocholic acid (DHCA) was used as the internal standard. The specific absorption bands at 1420 cm−1 and 1705 cm−1 were chosen for TNX and DHCA, respectively. The concentration range between 0.15-0.35 % w/w in KBr disc showed compliance with Beer's law.

Effect of phosphatidylglycerol on the in vitro percutaneous drug penetration through the dorsal skin of guinea pigs, and analysis of the molecular mechanism, using (ATR-FTIR) spectroscopy

Standard in vito skin percutaneous penetration methods using excised guinea pig dorsal skin were employed, to characterize the penetration of a water-insoluble drug: tenoxicam (TEX), and a water-soluble drug: diclofenac sodium salt (DFS), enhanced by phosphatidylglycerol (PG); and an attenuated total reflectance fourier transform infrared (ATR-FTIR) spectroscopy was used to analyze the molecular mechanism of the drug penetration route. The C-H bond stretching absorbance frequency shift in the stratum corneum (SC) induced a higher and a broader absorbance, and the shift was dependent on the PG concentrations. The percutaneous penetration of TEX was dependent on the PG concentration (up to 6%). The enhancing mechanism of PG to TEX may not only increase the diffusion coefficient (D) and the partition coefficient (K) in the percutaneous TEX penetration but also increase fluidity of the route (intercellular lipid domain) for TEX, while that of PG to DFS, excepting 1%, PG system, may be increasing the D value in the percutaneous DFS penetration only. The percutaneous penetration of DFS was not dependent on the PG concentrations. Furthermore, the percutaneous penetration of TEX was proportional to the C-H bond stretching absorbance frequency shifts. In contrast, the percutaneous penetration of DFS was not proportional to the C-H bond stretching absorbance frequency shifts. Furthermore, the accumulation of TEX in skin was proportional to the C-H bond stretching absorbance frequency shifts. The striking parallel between the enhancement of the percutaneous penetration of TEX and the measured SC lipid fluidity shifts caused by PG, suggests that the transdermal water-insoluble drug penetration may be ultimately related to the SC lipid structure. Overall, these results suggest that PG mainly affects the intercellular lipid pathway (lipid-rich domains).

Effect of nonionic surfactants on the percutaneous absorption tenoxicam.

The effect of 14 types of nonionic surfactants on the permeation of Tenoxicam (TEN) through guinea pigs from propylene glycol solution was investigated in vitro. The flux of TEN was significantly enhanced by polyoxyethylene alkyl ether and polyoxyethylene monoalkyl carboxylate as hydrophilic surfactants, and by polyglyceryl trialkylate, glyceryl monoalkylate, sorbitan monoalkyl carboxylate and sorbitan trialkyl carboxylate as hydrophobic surfactants. In the presence of these surfactants, the flux was increased about 2 to 4 times, as compared to the flux without them. The mechanism of nonionic surfactant action was analyzed and classified by recent methods. the including HLB of surfactants, the solubility of the drugs in vehicle and the hemolysis of erythrocytes. The results suggested that vital factors in the enhancement of skin permeation by nonionic surfactants include the affinity of the surfactants to the stratum corneum, the solubility of the drugs in vehicle and the penetration of surfactants to the stratum corneum.

Piroxicam has at least two epitopes for contact photoallergy

We have demonstrated previously in guinea pigs that the induction of photocontact sensitivity to piroxicam (PXM) also induces a state of cross-reactive contact hypersensitivity to two compounds having structurally related elements, thimerosal (TMS) and thiosalicylate (TOS). The present study was conducted to determine whether oral administration of TOS would desensitize guinea pigs previously photosensitized with PXM. At the same time, the spectrum of reactivities against these compounds and against tenoxicam (TXM) which resembles only piroxicam was assesed by appropriate sensitizing and eliciting protocols. As expected, animals photosensitized to PXM developed reactivities against all four compounds, PXM and TXM (photosensitivity) and TMS and TOS (contact sensitivity). By contrast, photosensitization with TXM induced cross-reactivity only against PXM. Moreover, the induction of contact sensitivity against TMS or TOS induced photosensitive cross-reactivity to PXM, but not to TXM. Finally, the oral administration of TOS produced a transient desensitization only for TMS and TOS. These results suggest that photosensitization with PXM induces two distinct reactivities. The first reactivity cross-reacts with TMS and TOS and is suppressible with orally administered TOS. The second cross-reacts only with TXM and is not suppressible with oral TOS. We conclude that PXM acquires at least two distinct immunogenic epitopes when exposed to UVA irradiation.

Midday dosing of tenoxicam is recommended

Midday dosing of tenoxicam is recommended

Tenoxicam compares well with piroxicam and diclofenac

Tenoxicam compares well with piroxicam and diclofenac

No differences found between tenoxicam and diclofenac in ankylosing spondylitis

No differences found between tenoxicam and diclofenac in ankylosing spondylitis

Tenoxicam: references since 1986

Tenoxicam: references since 1986

Tenoxicam - a well tolerated once-daily NSAID

Tenoxicam - a well tolerated once-daily NSAID

Tenoxicam: Roche's anti-inflammatory has recently been approved in its first market, Switzerland

Tenoxicam: Roche's anti-inflammatory has recently been approved in its first market, Switzerland