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Objective To determine efficacy and safety of patient-controlled intravenous analgesia (PCIA) with tramadol and lornoxicam for postoperative analgesia, and its effects on surgical outcomes in patients after thoracotomy. Summary of background data Adequate pain relief after thoracic surgery is of particular importance, not only for keeping patients comfortable but also for reducing the incidence of postoperative complications. PCIA with tramadol and lornoxicam could be an acceptable alternative to patient-controlled epidural analgesia (PCEA) for pain management after thoracotomy. Methods The records of patients who underwent thoracotomy for lung resection between January 2014 and December 2014 at our institution were reviewed. The patients were divided into 2 groups according to postoperative pain treatment modalities. Patients of PCEA group (n = 63) received PCEA with 0.2% ropivacaine plus 0.5 μg/mL sufentanil, while patients in PCIA group (n = 48) received PCIA with 5 mg/mL tramadol and 0.4 mg/mL lornoxicam. Data were collected for quality of pain control, incidences of analgesia-related side effects and pulmonary complications, lengths of thoracic intensive care unit stay and postoperative hospital stay, and in-hospital mortality. Results Pain at rest was controlled well in both groups during a 4-day postoperative period. Patients in PCIA group reported significantly higher pain scores on coughing and during mobilization in the first 2 postoperative days. The incidences of side effects and pulmonary complications, in-hospital mortality, and other outcomes were similar between groups. Conclusions PCIA with tramadol and lornoxicam can be considered as a safe and effective alternative with respect to pain control and postoperative outcomes after thoracotomy.

Стаття присвячена проблемі головного болю у пацієнтів, які перенесли інсульт. Для постінсультного головного болю характерне зростання частоти нападів при збільшенні давності інсульту. Найбільш поширеним видом постінсультного головного болю є головний біль напруження. Високоефективним методом лікування є використання нестероїдних протизапальних засобів (лорноксикам) та антидепресантів (сертралін, есциталопрам та ін.).

Біль є найчастішим симптомом у загальній медичній практиці. Больовий синдром при остеоартриті характеризується поєднанням болю механічного, запального, а також нейропатичного характеру, що викликає стійкий хронічний його перебіг. Водночас вірогідно встановлено, що біль є одним із факторів ризику і прогресування остеоартриту. Згідно з останніми рекомендаціями з лікування ­остеоартриту, нестероїдні протизапальні препарати (НПЗП) потрібно застосовувати як знеболюючий і протизапальний засіб тривалими (постійними або переривчастими) циклами. На сьогодні питання анальгетичного потенціалу НПЗП поступаються питанням їх клінічної безпеки. Проблема контролю безпеки є кардинальним аспектом раціонального використання НПЗП. Проаналізовано останні дослідження, що підтверджують гастроінтестинальну і кардіоваскулярну безпеку лорноксикаму при тривалому застосуванні. Лорноксикам поєднує оптимальний профіль анальгетичного потенціалу та безпеки в аспекті тривалого, перманентного застосування, що робить його препаратом вибору для лікування остеоартриту. Сприятливий профіль безпеки лорноксикаму є наслідком того, що препарат є збалансованим інгібітором циклооксигенази-1/-2 і має відносно короткий період напіввиведення порівняно з іншими НПЗП, що знижує ризик його акумуляції.

Lornoxicam is a drug that is used for various diseases related to inflammation and pain. In the clinical application of lornoxicam, studies on individualized pharmacotherapy and modeling considering interindividual pharmacokinetic variability have rarely been reported. In this study, a population pharmacokinetic modeling study was performed with a search for effective covariates that could explain the interindividual pharmacokinetic variability of lornoxicam. Based on the bioequivalence results of 28 healthy Korean males and the identification of various genetic and physicochemical parameters of the participants, a population pharmacokinetic modeling of lornoxicam was performed by a non-linear mixed-effects modeling method using Phoenix NLME. The pharmacokinetics of lornoxicam in the population were well explained by the one-compartment basic model with first-order absorption/elimination and lag-time reflected in the absorption phase. The covariates investigated to account for interindividual pharmacokinetic variability were extended to the established basic model. Creatinine clearance (CrCl), which is used as a general indicator of renal function, was positively correlated with the clearance of lornoxicam, and this was identified as a valid covariate in the population pharmacokinetic model of lornoxicam. According to the genetic polymorphism of CYP2C9, a significant difference was confirmed in the clearance of lornoxicam, which was also a valid covariate in the model. Considering that the metabolism of lornoxicam is mainly by the CYP2C9 enzyme and a significant proportion of the metabolite is excreted in the urine through the kidneys, it was appropriate to explore the CYP2C9 genotype and CrCl levels as covariates in the population pharmacokinetic model of lornoxicam. Through the results of this study, individualized and effective lornoxicam therapy taking into account the genotype and degree of renal function of individuals will be possible in the future.

The aim of the present work was to develop sustained release Lornoxicam matrix tablets with polymers like HPMC K15M, Ethyl cellulose, and Crospovidone as carriers in varying quantities. Direct compression was used to make matrix tablets. Various assessment parameters, such as hardness, friability, thickness, percent drug content, weight variation, and so on, were applied to the prepared formulations. In vitro dissolution studies were carried out for 24 hrs. The tablets were subjected to in-vitro drug release in (pH 1.2) for first 2 hrs. Then followed by (pH 6.8) phosphate buffer for next 22 hrs. And the results showed that among the six formulations FL3 showed good dissolution profile to control the drug release respectively. The drug and polymer compatibility were tested using FT-IR spectroscopy, which revealed that the drug was compatible with all polymers. It is also required to design an appropriate prolonged release formulation for Lornoxicam in order to maintain the drug's release. Hence by using the compatible polymers sustained release tablets were formulated and subjected for various types of evaluation parameters like friability, hardness, drug content and dissolution behaviour. Finally, the findings reveal that the prepared sustained release matrix tablets of lornoxicam have improved efficacy and patient compliance.

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated. Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release. Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model. In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n < 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model. Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

Background Tonsillectomy is one of the most common procedures in otorhinolaryngology practice where analgesics are required for pain-relief especially in children. To compare the efficacy of using peritonsillar infiltration of lidocaine Hcl versus intravenous preincisional lornoxicam in reducing post tonsillectomy pain. Results Prospective, randomized, double-blinded, placebo-controlled study. Ninety-nine patients from age 12 to 18 years old, prepared for tonsillectomy. Patients were randomly subdivided into three groups as 33 patient in each group to receive either lidocaine (group 1), lornoxicam (group 2), or saline as a placebo (group 3). Anesthesia was induced using intravenous fentanyl and propofol, while endotracheal intubation was facilitated with rocuronium and maintenance by halothan. Intraoperative bleeding, pain scores, interval until first order for analgesic. The postoperative complications including bleeding, hypoxia, nausea, and vomiting also were observed. Pain scores at rest were significantly lower in group 2 than groups 1 and 3 at all observation times. Similarly, pain scores were lower in group 2 during the first 5 postoperative hours. The mean time for rescue analgesic was 276 min in group 2, 91 min in group 1, and about 60 min in group 3. No significant differences were noted for intraoperative bleeding. Conclusion The use of lornoxicam 16 mg at preoperative phase gave good control of immediate post tonsillectomy pain. Level of evidence 3b

A selective and sensitive reverse phase High Performance Liquid Chromatographic method has been developed and validated for the estimation of lornoxicam in bulk, pharmaceutical dosage forms and in dissolution samples. The analysis was performed isocratically on an Inertsil column (250* 4.6 mm, 5 µm) using a mass spectrometric compatible mobile phase of 10 mM ammonium acetate: acetonitrile (50:50 V/V) at a flow rate of 1 mL/min.The detection wavelength was 290 nm. The retention time was found to be 4.573 min for lornoxicam. The linearity of the method has been satisfied with Beer Lambert’s law in the concentration range of 5-25 µg/mL with a correlation coefficient of 0.9988. The mean recoveries assessed for lornoxicam were in the range of 100.39-101.86 %, indicating good accuracy of the method. The limit of detection and limit of quantification were found to be 0.03 and 0.11 µg/mL, respectively. The developed method has been statistically validated in accordance with ICH guidelines and found to be mass spectrometric compatible, simple, precise, and accurate with the prescribed values. Thus, the proposed method was successfully applied for the estimation of lornoxicam in routine quality control analysis of bulk, formulations and in dissolution samples.

Using simple, precise, and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method, the synchronous of lornoxicam (LOR) and paracetamol (PCM) in the unite dosage form in the tablet has been established and confirmed. Acetonitrile: methanol: water is the mobile phase of the RP-HPLC method (pH adjusted with orthophosphoric acid), pH 3.8 (50:30:20 v/v/v), a diode array detector tuned to 290 nm was used to detect the signal. For LOR and PCM, chromatographic technique linearity was obtained in the concentration, ranges of 2-40 and 8–150 g/mL, respectively. In HPLC techniques, the recoveries were in the range of 99.85 0.0642 percent for LOR and 99.73 0.187 percent for PCM. Both approaches may be used to analyze the medicines in a pharmaceutical formulation regularly. The results of the analysis were statistically verified. KEYWORDS: linearity, validation, oxicam, N-methyl Aspartate

Objective: The aim of the study was to develop sustained release pellets of lornoxicam using Eudragit RLPO and Eudragit RSPO to reduce the dosing frequency. Methods: The sustained release pellets of lornoxicam were prepared by extrusion–spheronization technique using Eudragit RLPO and Eudragit RSPO as release retardant polymers and microcrystalline cellulose as spheronizing agent. A 32 Full factorial design was applied to investigate the combined effect of the two independent variables i.e. concentration of Eudragit RLPO (X1) and concentration of Eudragit RSPO (X2) on the dependent variables, In vitro drug release at 1h (Y1), In vitro drug release at 4 h (Y2) and In vitro drug release at 12 h. (Y3). Results: The optimized formulation (F0) show in vitro drug release 11.24±1.21 %, 43.69±1.28 %, 82.69±1.74 % and 100.24±1.56 % at 1 h, 4 h, 12 h and 24 h respectively. Drug excipients compatibility study by FTIR showed no interaction between drug and excipients. Eudragit RLPO and Eudragit RSPO had a significant effect on in vitro drug release. Conclusion: From all parameters and experimental design evaluation, it was concluded that the drug release rate decreased with an increase the concentration of Eudragit RLPO and Eudragit RSPO. SEM Photomicrograph of pellets revealed that the surface was rough and the pellets were spherical shaped in nature. The in vitro release kinetics revealed higuchi model is followed and drug release is by anamolous diffusion.

Among N-(4-methoxybenzyl)-4-methyl-2.2-dioxo-1H-2 λ6.1-benzothiazine-3-carboxamide derivates, the compound methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid (compound NI-9) with pronounced analgesic and anti-inflammatory activities, which was superior to those of diclofenac and lornoxicam in the model of carrageenan edema. The aim of the study was to investigate the analgesic effect of benzothiazine-3-carboxamide derivative on different models of somatic and neuropathic pain syndromes. The study was performed on 91 male Wistar rats. Compound NI-9 and reference drugs meloxicam, diclofenac and gabapentin were administered intragastrically at doses of 3, 5, 8 and 5 mg/kg, respectively, corresponding to their ED50 in analgesic activity. Acetic spasms in mice, a model of thermal irritation of the tail flick in rats, as well as adjuvant arthritis and diabetic polyneuropathy were selected as models of pain syndromes. The results were processed in the program STATISTICA 10.0 using non-parametric methods. The results showed that methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid (compound NI-9) has a pronounced analgesic effect on various models of pain syndromes, both somatic and inflammatory. and of neurogenic origin. The analgesic activity of the compound NI-9 in the model of acetic acid cramps in mice and thermal irritation in rats was 38.09 and 49.75 %, respectively, which was higher than that of meloxicam (36.73 and 45.68 %), and inferior to diclofenac (41.95 and 55.95 %). In the model of the systemic inflammatory process (adjuvant arthritis), the analgesic effect of NI-9 was statistically superior to meloxicam and diclofenac (43.32 % vs. 26.26 and 33.69 %). In a model of neuropathic pain syndrome (diabetic neuropathy), the analgesic effect of methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid was greater than meloxicam (18.96 vs. 13.34 %), but this figure was lower than that of gaapentin (20.83 %). Further in-depth study of its pharmacodynamics and toxicity will be the theoretical basis for the development on the basis of this biologically active compound of the original drug with analgesic and anti-inflammatory activities.

The present study was aimed to prepare and characterize new cocrystals of lornoxicam (LORX), a BCS class II drug employing 1,3-dimethyl urea (DMU) as a coformer to improve physicochemical, pharmaceutical, and pharmacokinetic performance.A screening study was conducted by employing three techniques viz. neat grinding, liquid-assisted grinding (LAG), and solvent evaporation (SE) using different drug-coformer molar ratios (1:1, 1:2, and 1:3). Samples were characterized by DSC, PXRD, ATR-FTIR, SEM, intrinsic dissolution rate (IDR) studies, compressional studies, and pharmacokinetic studies.LAG and SE were found successful in ratio 1:3 and IDR showed approximately 28- and 19-fold increase, respectively in 0.1 N HCl (pH 1.2) and buffer (pH 7.4) as compared to pure LORX. The cocrystal exhibited good tabletability and was ∼2.5 times that of LORX at 6000 Psi. Dissolution profiles of tablets of cocrystal increased (56% and 100% at pH 1.2 and 7.4, respectively in contrast to those of physical mixture (PhyMix) (∼35% and ∼10%) and pure LORX (∼17% and ∼7%) within 60 min. TheThe study indicates that cocrystallization with DMU can concomitantly improve tabletability, dissolution rate, and

Aim: The aim of this study was to evaluate the efficacy of various routinely used analgesics in the management of pulpal pain preoperatively. Materials and Methods: A total of 150 patients were randomly selected and divided into five groups each. At initial visit, a self-administered questionnaire was given, and patients were asked to mark on the Visual Analog Scale (VAS) indicating severity of pain at that moment which is taken as a pretreatment VAS score. Group I patients received aceclofenac + paracetamol, Group II: ketorolac tromethamine, Group III: lornoxicam + paracetamol, Group IV: tramadol + paracetamol, and Group V: paracetamol. All the patients are requested to record their pain levels at 4 h, 6 h, 8 h, 24 h, and 48 h by means of VAS scores before and after treatment. Results: There was no significant decrease in frequency of pain when compared in the first three groups, whereas in Group III and Group IV, the patients experienced an effective reduction in pain because of sustained releasing ability of these drugs. Overall, there was no statistically significant differences among all the groups. Conclusion: This study suggests that there was no significant difference in reduction of pain preoperatively. However, lornoxicam + paracetamol and tramadol + paracetamol were effective because of their sustained releasing ability. Ketorolac was effective to reduce the pain for shorter duration. Paracetamol can be advised in compromised patients where safety is concerned.

Objective: To investigate the potential of novel polymer isolated from fruit Artocarpus heterophyllus for mucoadhesion and sustained release action. Microspheres containing Lornoxicam formulated using isolated polymer offered a suitable, practical approach to achieve a prolonged therapeutic anti-inflammatory effect by continuously releasing the medication over extended period of time. Materials and Methods: D-Optimal design was applied to optimize the fruit polymer and sodium tripolyphosphate concentration which was used as a cross-linking agent. Result: Fruit polymer and sodium tripolyphosphate concentration has significant impact on % entrapment efficiency, mucoadhesivity, and in vitro release. Differential scanning calorimetry and infrared spectroscopy results indicates that no interaction between drug and excipients. Polynomial models were validated using one way ANOVA and results indicated that isolated fruit polymer and sodium tripolyphosphate used have significant effect on selected response (p

Objective: To design a controlled topical delivery system of lornoxicam (LX) in order to enhance skin permeation and treatment efficacy. Nanosponges were selected as a novel carrier for this purpose. Methods: Nanosponges were formulated via the emulsion solvent evaporation method using ethyl cellulose (polymer) and polyvinyl alcohol (surfactant). Nanosponge dispersions were characterized for colloidal properties, entrapment efficiency and in vitro release study. The nanosponge formulation (LS1) was then incorporated into carboxymethyl cellulose sodium hydrogels and evaluated for pH, viscosity and in vitro drug release. Skin irritation was evaluated, and anti-inflammatory activity was assessed via rat hind paw edema method. Results: Nanosponges were in the nano-sized range and attained a uniform round shape with a spongy structure. LS1exhibited the highest LX release after 6 h, so it was incorporated as hydrogel. Formulated hydrogels showed acceptable physicochemical parameters (pH, drug content and rheological properties). Skin irritation testing proved LX-loaded nanosponge hydrogel formulation (G1) to be non-irritant. In vivo study revealed an enhanced anti-inflammatory activity of G1 for 6 h (p

Objective: A rapid and environmental friendly microemulsion liquid chromatographic method was developed for simultaneous quantification of morphine (MOR), tramadol (TRA) and lornoxicam (LOR) in biological fluids. Methods: Microemulsion used in this study was an aqueous solution containing sodium dodecyl sulfate (0.12 M), n-propanol (10%), ethyl acetate (0.75%), tri-ethyl amine (0.3%), orthophosphoric acid (0.15 %) and the pH was adjusted to 3.0 with orthophosphoric acid. Chromatographic separation was carried out on a monolithic C18 column and a mobile phase flow rate of 1.0 mL min−1 was applied throughout the analysis. The data was monitored using UV-detection mode at a wavelength of 220 nm. Results: Under the optimized conditions, all the studied drugs were well resolved and completely eluted within 6 min. The proposed method was linear over the concentration ranges of 0.5−100, 0.75−125 and 0.25−50 μg mL−1; limits of detection of 0.074, 0.086 and 0.056 μgmL−1 and limits of quantification of 0.21, 0.28 and 0.12 were recorded for TRA, LOR, and MOR, respectively. The developed method was fully validated according to the ICH guidelines. The method was successfully utilized to estimate the tested analytes in plasma and urine samples, which were directly injected into the chromatographic system after suitable dilution with the microemulsion. Conclusion: The developed method is considered to be very efficient to analyze the cited drugs in different biological fluids with low running costs and short analysis time.

Failure mode critical effect analysis and design of experiment-based high performance thin layer chromatography (HPTLC) method has been developed for simultaneous estimation of lornoxicam (LOC) and eperisone hydrochloride (EPR). Failure modes were identified on the basis of prior knowledge and experimental data with the help of Ishikawa diagram for the development of method. The criticality of failure mode was assessed by giving risk priority number and criticality rank on the basis of preliminary experimental trials. The identified critical failure modes were analyzed for their effect by design of experiment (DoE)-based Plackett–Burman screening design. From 11 critical factors, the volume of methanol and modifier in mobile phase composition were found as critical failure modes. Critical failure mode was further analyzed by DoE based on central composite design for study of their relationship with resolution of both drugs. Quadratic model suggested by design was further used for failure mode risk control and navigation of design space for a resolution of both drugs more than 1.5. Failure mode risk control strategy was set for robust HPTLC method for simultaneous estimation of both drugs in laboratory mixture. Developed and validated HPTLC method was applied for assay of LOC and EPR in their laboratory mixture and assay values were found in good agreement with a spiked amount of drugs.

Background The goal of the proposed study was to validate a rapid, simple, an accurate, robust, and sensitive bioanalytical method for quantifying Meloxicam and Lornoxicam (as internal standard) in rabbit plasma. Result Limit of detection and limit of quantification for Meloxicam were found to be 0.0081 and 0.1035 μg mL−1, respectively. The bioanalysis was continued according to standard guidelines and successfully used for bioavailability studies of meloxicam after single dose administration of pure drug and the formulation in rabbit plasma. Finally, obtained results proved its simplicity and an efficiency to be applied for the therapeutic drug monitoring and bioequivalence studies. Conclusion Therefore, the set RP-HPLC bioanalysis is simple, convenient, and acceptable to analyze meloxicam in bulk and pharmaceutical formulations in rabbit plasma. Graphical abstract

Rheumatoid arthritis (RA) is an autoimmune disease associated with severe joint pain. Herein, we report lornoxicam loaded cellulosic microsponge gel formulation with sustained anti-inflammatory effects that are required to manage arthritic pain. The microsponges were formulated using quasi emulsion-solvent diffusion method employing four different surfactant systems, namely polyvinyl alcohol (PVA), Tween80, Gelucire 48/16 and Gelucire 50/13. All the lornoxicam loaded microsponge formulations were extensively characterized with a variety of analytical tools. The optimized microsponge formulation was then converted into gel formulation. The lornoxicam loaded microsponge gel formulation had adequate viscosity and sufficient pharmaceutical properties as confirmed by the texture analysis and the drug release followed Super case II transport. It is noteworthy that we described the preparation of a new cellulosic polymers based microsponge system for delivery of lornoxicam to provide quick as well as lasting (sustained) anti-inflammatory effects in rats using carrageenan induced rat paw edema model. We were able to demonstrate a 72% reduction in inflammation within 4 h using the optimize transdermal gel formulation utilizing Transcutol P as permeation enhancer and with the aid of skin micro-piercing by microneedles, hence, demonstrating the potential of this microsponge gel formulation in arthritis management.

The objective of the study was to develop microneedle (MN) patch, with suitable properties to ensure the delivery of a therapeutic level of lornoxicam (LXM) in a period suitable to replace parenteral administration in patients, especially those who fear needles. The used polymers were cold water-soluble polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) of low molecular weight with PEG 400 as plasticizer and Tween 80 (to enhance the release) using micro molding technique. Patches were studied for needle morphology, drug content, axial fracture force measurement and drug release while the optimized formulas were further subjected to pH measurement, folding endurance, ex vivo permeation study, histopathology study, stability study and compatibility study. The patch with 11:1 ratio of PVA to PVP, 30% solid content, 5% PEG 400 and 3% Tween 80 resulted in axial needle fracture force value of (1.35 N) which is suitable for skin penetration. The release was fast with almost 100% of drug released in 60 minutes. The permeation was enhanced significantly with a steady state flux of about 3.1 times that of the solution. The lag time of MN is shorter in comparison with ordinary patch. Histopathology studies demonstrated the safety of the formulation, both stability studies and compatibility studies showed the suitability of the formulation. The results indicated that LXM microneedle patch could enhance drug permeation while achieving fast and painless administration. Keywords: Microneedle patch, Polyvinyl alcohol, Polyvinylpyrrolidone, Fracture force, Lornoxicam.

Objective: This study aimed to enhance the oral solubility and dissolution of poorly soluble lornoxicam by anti-solvent precipitation, and the manufacture of oral tablets by the phase transition method. Methods: The solvent was mixture of polyethylene glycol 400 and absolute ethanol. Three stabilizers Inutec SP1, Pluronic F127, Sucrose ester S1670 at two concentrations and two matrix formers Mannitol, and Avicel PH102 were used to obtain 12 formulae. The formulae were characterized regarding their infrared spectroscopy (IR), differential scanning calorimetry (DSC), particle size (PS) measurement, drug content and dissolution. Further characterizations were done for the optimum formula by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Four tablet formulae were manufactured by phase transition method. The optimum tablets (T3) were evaluated through hardness, drug content, disintegration, dissolution, IR, and stability studies. Finally, (T3) was compared to conventional tablets in New Zealand rabbits using crossover design. Results: The dissolution rate for the prepared formulae was enhanced, from 3.44 to 5.96 folds. Statistical significance was obtained using one and two way ANOVA among formulae. The optimum tablet formula (T3) had hardness 5.637±1.57 kg, drug content 90.424±1.19%, disintegration time 341.5±9.62 s and the drug dissolved 72.107±0.0025%. Stability, after one month storage of the selected tablets at (25 °c/60% relative humidity), was satisfactory. The absorption extent of lornoxicam from (T3) compared to the conventional tablets was higher. Conclusion: Taken together, the obtained results confirmed successfully the potential of the promising formula (T3), over the conventional tablets of lornoxicam.

Osteoarthritis is a chronic joint disease characterized by chronic inflammation, progressive destruction of articular cartilage, and subchondral bone sclerosis. When compared to individual treatment, the combined administration of genes and small-molecule drugs for osteoarthritis may not only provide superior inflammation control and pain relief, but may also repair cartilage damage. Here, cationic liposomes (CL) were used to deliver small hydrophobic drugs and microRNA into chondrocytes to treat osteoarthritis. Lornoxicam cationic liposomes (Lnxc-CL) were prepared by film dispersion, and loaded with microRNA-140 (miR-140) by electrostatic interaction to obtain cationic liposomes co-loaded with lornoxicam and miR-140 (Lnxc-CL/miR-140). The prepared Lnxc-CL/miR-140 had a particle size of 286.6 ± 7.3 nm, polydispersity index (PDI) of 0.261 ± 0.029 and zeta potential of 26.5 ± 0.5 mV and protected miR-140 from RNase degradation for 24 h. Lnxc-CL/miR-140 was evaluated for its ability to regulate gene expression in chondrocytes in vitro and to provide in vivo therapeutic effects for knee osteoarthritis in rats. The results of in vitro uptake experiments and polymerase chain reaction (PCR) analysis showed that Lnxc-CL/miR-140 efficiently delivered miR-140 into chondrocytes and up-regulated the expression of miR-140 and COL2A1 mRNA. Pharmacodynamics studies demonstrated that Lnxc-CL/miR-140 effectively treated osteoarthritis by eliminating joint inflammation and repairing damaged cartilage cells, with superior therapeutic effects compared to Lnxc or miR-140 alone. Overall, the findings of this study support the co-delivery of Lnxc and miR-140 with cationic liposomes as a potential new therapeutic strategy for the treatment of osteoarthritis.

Background: Lornoxicam is widely used for its anti-inflammatory, analgesic and antipyretic properties. However, it suffers from the limitations of possessing a relatively short elimination half-life ranging from 3 to 5 h, thereby; leading to repeated dosing which in turn may cause local irritation and ulceration. In addition, LXM also exhibits pH-dependent solubility. Effective management of inflammation in diseases such as arthritis requires the formulation of delivery systems that may be able to provide immediate release of drug for instant relief which shall be maintained for a prolonged period. Objective: The present research work was aimed to modify the release pattern of poorly water-soluble drug Lornoxicam by designing a biphasic tablet comprising of solid dispersion (immediate release form) and microspheres (controlled release form) for the effective management of inflammation. Methods: The solid dispersion (SD) was prepared by melting method using PEG 4000 and tween 80 and formation was confirmed by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies. Polymeric microspheres loaded with Lornoxicam were prepared by ‘Emulsion Solvent-Evaporation’ method using Eudragit S-100 and Eudragit L-100. Microspheres (MS) were evaluated for drug entrapment efficiency, drug loading, drug content, particle size and in vitro release behaviour. Optimized microspheres (polymer concentration 0.5% w/v and drug concentration 0.1% w/v and solid dispersion (drug: PEG 4000: 4:6) were compressed in the ratio of 1:3 to produce biphasic tablet. The prepared tablets were evaluated for various pre-compression and post-compression parameters. Anti-inflammatory activity of the F4, M6 and the combination of SD and Microspheres in a ratio of 1:3 was carried out by Carrageenan induced paw edema method in Wistar rats. Results: The solid dispersions prepared by melting technique showed an enhanced dissolution rate as compared to the pure drug. LXM microspheres exhibited a sustained drug release. In vitro release of lornoxicam from biphasic tablets showed that 20% of the drug released at the end of first one hour, followed by 33% release at the end of 4th h and maximum release of 94.1% at the end of 10 h. The prolonged effect continued till the end of 12 h. Results showed that the mixture of MS + SD exhibited 48% inhibition in 30 min which is increased to 88.63% at the end of 4 h which can be explained by initial burst release from the soluble layer of SD (which gave initial required effective concentration of Lornoxicam) followed by sustained release from matrix of microspheres (which maintained required level of Lornoxicam in blood). Conclusion: A successful modification of the release pattern of LXM was achieved by designing a biphasic tablet comprising of solid dispersion for the effective management of inflammation.

The purpose of this study was to investigate the effect of omega-3 poly unsaturated fatty-acids co-administered with the therapeutic dose of lornoxicam on liver of healthy rats. Twenty-eight adults male rats weighing 180-200g were used in this study and the animals were randomly divided into four groups of seven rats each. Group I: negative control/rats intraperitoneally injected with normal saline in a dose 5ml/kg/day; Group II: rats intraperitoneally injected with lornoxicam at dose 0.7 mg/kg/day; Group III: rats orally-administered omega-3 only at a dose 185mg/kg/day; Group IV: rats co-administered omega-3 (185mg/kg/day) orally and intra-peritoneal injection of lornoxicam (0.7 mg/kg/day). Duration of treatment was 14-day; and at day 15 of the study, the liver of each rat was excised for the preparation of tissue-homogenate to be utilized for the estimation of ALT, AST, TNF-alpha and IL-10. Omega-3 can reduce signs of inflammation through the reduction- of TNF-alpha level and elevation of IL-10 with a significant reduction in ALT enzyme activity level in rats' liver tissue homogenate. In conclusion, Omega-3 poly-unsaturated fatty-acids may have a protective effect against hepatocytes inflammation when co-administered with lornoxicam.

Objectives Simple, specific, accurate, precise, sensitive, and cost effective spectrophotometric methods were developed and validated for quantification of the drugs lornoxicam (LOR) and mesalamine (MES) in pure form and in pharmaceutical formulations. Materials and methods A Shimadzu UV-1800 double-beam UV-Visible spectrophotometer having a spectral bandwidth of 0.1 nm with wavelength accuracy ±0.1 nm with a pair of 1 cm path length matched quartz cells was used to measure the absorbance of the resulting solution. Method I was used for the quantification of LOR, based on measurement of the absorbance of bluish green chromogen complex at 760 nm, which is formed by the reaction of LOR with ferric chloride and potassium ferricyanide (redox technique). Method II was used for the quantification of MES, based on measurement of the absorbance of yellow chromogen at 400 nm, which is formed by the condensation reaction of the primary amino group of MES with salicylaldehyde reagent (SA) (Schiff base formation). Results Both methods obeyed Beer's law in the concentration range of 0.5-4.5 μg/mL and 0.2-1.7 μg/mL with good correlation coefficients of 0.9974 and 0.998 for methods I and II, respectively. Conclusion The developed method is simple, sensitive, and specific, which was validated statistically as per ICH guidelines, and can be used in the routine analysis of LOR and MES in pharmaceutical dosage forms.

GIT irritation is prominent limitation with the use of Non-steroidal anti-inflammatory drugs (NSAID’s). There is rising interest in designing formulations which will deliver the drug at the site of action as topical gels, to avoid GIT irritation and other systemic side effects. Liquid Crystal phase has emerged as a novel material for the preparation of topical drug delivery system. In present study the attempt is made to prepare Lornoxicam loaded lyotropic liquid crystalline gel using glycerol monooleate. Glycerol monooleate is biocompatible, bioadhesive, penetration enhancer and sustain release agent. It also promotes ceramide extraction and enhancement of lipid fluidity in the stratum corneum region of the skin. Five formulation of lornoxicam were prepared and evaluated for parameters like drug content, viscosity, spreadability, Extrudability In-vitro drug release along with in vivo study. In-Vitro and Ex-Vivo drug release kinetics showed that there was 72.85% and 77.98% drug release within 48 hrs. Skin irritation test suggested that prepared formulation was safe for human use. In-Vivo evaluation of this formulation was done by carrageenan induced rat paw edema anti-inflammatory model. Keywords: Lornoxicam, GMO, Lyotropic liquid crystal, Anti-Inflammatory, Topical drug delivery

OBJECTIVE: To compare preemptive and postoperative analgesic efficacy of tramadol and lornoxicam administered before anaesthesia induction in lumbar discectomy. METHODS: This randomised, double-blind trial was conducted on 60 ASA I and II patients undergoing lumbar discectomy. Group L (n=30) received 3×8 mg day(−1) lornoxicam, and Group T (n=30) received 3×1.5 mg kg(−1) day(−1) tramadol. A verbal rating scale (VRS), the duration of effective analgesia, the number of additional analgesics used, adverse effects and patient satisfaction were evaluated at the postoperative 30(th) minute and 1(st), 2(nd), 4(th), 6(th), 8(th), 12(th) and 24(th) hours. RESULTS: There were no significant differences between Groups L and T regarding demographic and clinical characteristics, the number of additional analgesics and the duration of effective analgesia, adverse effects and patient satisfaction. VRS scores of the patients in Group T were significantly higher than those in Group L at the postoperative 30(th) minute (p=0.050) and the 1st hour (p=0.005). CONCLUSION: Lornoxicam, which was used for preemptive and postoperative analgesia in lumbar disc surgery, had provided adequate and effective analgesia such as tramadol. Moreover, preemptive analgesia was quite effective in prevention and treatment of postoperative pain.

Background Intense pain can last several days after tonsillectomy. It is often undertreated and improved analgesic strategies that can be safely used at home are needed. Methods We conducted a systematic review and meta-analysis on the effectiveness of systemic medications used for post-tonsillectomy pain in adult and adolescent (13 yr old) patients. Studies were identified from PubMed, the Cochrane Library, and by hand searching reference lists from studies and review articles. Randomised, double-blind, placebo-controlled studies reporting on pain intensity or use of rescue analgesia were included. Results Twenty-nine randomised controlled trials representing 1816 subjects met the inclusion criteria. Follow-up time was ≤24 h in 15 studies, in which the majority were taking nonsteroidal anti-inflammatory drugs. Thirteen studies were suitable for meta-analysis. In pooled analysis, paracetamol, dexamethasone, and gabapentinoids reduced pain intensity on the day of operation. In individual studies, ketoprofen, ibuprofen, lornoxicam, parecoxib, rofecoxib, indomethacin and dextromethorphan reduced pain intensity, need for rescue analgesics, or both on the day of operation. Oral celecoxib for 2 postoperative weeks or i.v. ketamine on the day of operation were not effective at the studied doses. Dexamethasone in multiple doses provided analgesia beyond 1 postoperative day. Pain was moderate to strong in both study and control groups during the first postoperative week. Conclusions Single analgesics and dexamethasone provide only a weak to moderate effect for post-tonsillectomy pain on the day of operation and thus a multimodal analgesic strategy is recommended. Short follow-up times and clinical heterogeneity of studies limit the usefulness of results.

Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class. It belongs to BCS class II substance with low solubility and high permeability. The aim of current research is to formulate solid dispersion incorporated Fast disintegrating tablets of Lornoxicam to enhance the dissolution rate and aqueous solubility and to enable faster onset of action. Solid dispersions are prepared with polymers like Kolliwax GMS, Soluplus and HPMC in three different ratios 1:1:1, 1:2:1 and 1:3:1. Formulations were characterized for drug content studies, drug release studies, and drug-polymer interactions using Fourier transform infrared spectroscopy (FTIR) spectrum. The solid dispersions can be evaluated by in-vitro dissolution studies. The optimized solid dispersion SD9 was further used to prepare fast disintegrating tablet by direct compression method using 33 Response surface method (3 variables and 3 levels of superdisintegrants) by using Design of experiment software with superdisintegrants like locust bean gum, gum karaya, Plantago ovata. The values of pre-compression parameters evaluated were within prescribed limits that indicated good free flowing properties. The data obtained of post-compression parameters such as weight variation, hardness, friability, content uniformity, disintegration time (33 sec) and percentage drug release was maximum in LF24 (99.21±1.87%) within 10 minutes and was found to superior over Marketed formulation i.e., 87.27±0.27 %. From in vivo bioavailability studies the best formulation has shown Tmax of 1.0 h which was highly significant (P < 0.05) when compared with marketed formulation 2.5 h. The statistical significance was assessed by one-way analysis of variance. Therefore, the solid dispersions incorporated fast disintegrating tablets of Lornoxicam can be successfully used for improvement of dissolution, resulted in faster onset of action as indicated by in vivo studies. It can be concluded that fast disintegrating tablets using Lornoxicam solid dispersion could be used to improve better patient compliance with immediate action in the effective management of pain and inflammation.

Lornoxicam (LOR) is a non-steroidal anti-inflammatory drug known to induce hepato-renal toxicity. The following study aimed to investigate the adverse effect of LOR in oxidative status beside biochemical and histological examination of Liver and kidney tissue as well as the protective effect ofDill. Thirty six male Wister albino rats were randomly divided into main four groups of nine rats each were used; G(1)Control group and they were administered 0.5ml of saline orally for 21 consecutive days, G (2):they were administered 2g/kg dill orally for 21consecutive days, G (3): they were administered 1.3 mg/kg body weight/day of LORintraperitonially for 21 consecutive days, G (4): they were administered 2g/kg dill orally concurrently with 1.3 mg/kg body weight/day of LOR. The results revealed that LOR induced significant increases in liver and kidney function parameters including AST, ALT, creatinine, and urea. Disrupted lipid metabolism also was observed in LOR-treated animals. Moreover, marked an increase in malondialdehyde (MDA) and decreases in glutathione (GSH) and catalase (CAT) following LOR-insult suggested a possible involvement of lipid peroxidation in LOR-induced hepatorenal toxicity.Oral administration of dill at the dose 2g/kg for 21 days was significantly mitigating these toxic effects.So it is concluded that dill has great hepatorenal, antioxidant and antiopoptotic effect.

Objective: Objective of the present investigation was to enhance the solubility and dissolution rate of poorly water-soluble drug lornoxicam using liquisolid technique with comparative determination of in vitro release profile of liquisolid compacts and conventional formulation of lornoxicam. Methods: Formulation was prepared by a liquisolid technique using different drug concentration in a liquid vehicle and different carrier/coating ratio. Prepared liquisolid compact was evaluated for Fourier transform infrared (FTIR) spectra analysis, differential scanning calorimetry (DSC), X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and in vitro dissolution study. Results: The result showed that liquisolid compacts of lornoxicam displayed significantly higher drug release rate as compared to pure drug and conventional tablet prepared. The results of both DSC and X-ray crystallography indicated loss of crystallinity of the drug upon formulated into the liquisolid compact. Conclusion: Dissolution rate of the drug from liquisolid compacts was affected by changing the drug concentration and excipient ratio. The liquisolid technique appeared to be a promising approach for improving the dissolution of poorly soluble drug lornoxicam.

Purpose: Post-operative pain after breast cancer surgery is a major problem and women undergoing mastectomy and breast reconstruction experience post-operative pain syndromes in approximately one-half of all cases. Patients who have undergone breast reconstruction after mastectomy can suffer from acute postoperative pain with moderate or strong tension. In some cases, chronic neuropathic pain syndromes may occur after surgery. Opioids are used to treat pain, with serious side effects. The systemic postoperative analgesic regimen as thiocochlicoside P.O. along with paracetamol and NSAIDs I.V., which may limit the administration of opioids without reducing pain relief, seems to be necessary. Materials and Methods: This study was a clinical trial randomizing 70 patients undergoing breast reconstruction. Two main protocols of systematic post-operative analgesia, one using thiocochlicoside (group A) and the other without them (group B), were used. Both groups received paracetamol X3 and lornoxicam X2 I.V. systematically. The pain measurement scale (NPS) used to measure post-operative pain. Likert scales were used to evaluate patient’s satisfaction and the difficulty from the side effects . An anonymous questionnaire was used for the data collection. Results: Statistically significant difference was found between pain on the day of surgery (p = 0.017) as well as the three subsequent days (p = 0.000). In group A , pain was reduced directly to half (Χ2 surgery pain = 93.888, p = 0.000) especially on the first post-operative day. In group A the satisfaction with analgesic treatment was higher than in group B (p = 0.002). Conclusion: The use of thiocochlicoside in post-operative analgesia in breast reconstruction after mastectomy contributes to reduce the pain intensity experienced by patients and to reduce the side effects of opioid analgesics as a result of reduced demand for opioid analgesics. Patients who received the analgesia using muscle relaxants-spasmolytic reported greater satisfaction.

Mahmoud H Teaima,1 Khaled M Abdel-Haleem,2 Rewan Osama,2 Mohamed A El-Nabarawi,1 Osama S Elnahas2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza, EgyptCorrespondence: Mahmoud H TeaimaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, EgyptTel +201005840264Email mahmoud.teaima@pharma.cu.edu.egSignificance: Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy.Purpose: This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon® and Lornoxicam®).Methods: Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q10 min. LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma.Results: Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst® (F2) had significantly (p< 0.05) the fastest DT (6.66± 1.52 s) and highest Q10 min (79.07± 2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products.Conclusion: The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.Keywords: oral disintegrating tablets, co-processed excipients, pitavastatin calcium, Lornoxicam, in-vivo pharmacokinetic study, liquid chromatography-mass spectrometry

(1) Background: Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antiphlogistic and antipyretic effects. The improved tolerance of lornoxicam due to the relatively shorter elimination half-life in comparison to other members of the oxicams may favor its application in the management of pain and inflammation in race dromedary camels. There are no studies conducted yet on the immunomodulatory or immunotoxilogic effect of lornoxicam in camels. Therefore, the current study aimed to evaluate the immunomodulatory effects of the cyclooxygenase inhibitor lornoxicam on some phenotypic and functional properties of camel blood leukocytes, (2) Methods: Using flow cytometry, blood leukocyte composition, monocyte phenotype, and antimicrobial functions of neutrophils and monocytes were analyzed ex vivo after a single dose injection with lornoxicam. In addition, the effect of in vitro incubation of camel blood with lornoxicam on leukocyte cell vitality and antimicrobial functions were evaluated, (3) Results: The injection of camels with a single dose of lornoxicam resulted in a significant change in their leukogram with reduced numbers of total leukocytes, neutrophils, eosinophils, monocytes, and lymphocytes. Within the lymphocyte population, the numbers of CD4+ T cells, T cells, and B cells decreased significantly in blood after injection of camels with lornoxicam. In addition, injection of lornoxicam resulted in decreased abundance of major histocompatibility complex (MHC) class II molecules and increased abundance of the scavenger receptor CD163 on blood monocytes, indicating an anti-inflammatory phenotype of monocytes. Functionally, administration of lornoxicam decreased the capacity of camel neutrophils and monocytes to uptake bacteria and to produce reactive oxygen species (ROS) after bacterial stimulation. Similarly, the in vitro whole blood incubation with lornoxicam resulted in reduced phagocytosis and ROS production activity of the camel blood phagocytes. Flow cytometric analysis of cell vitality, including cell necrosis and apoptosis, revealed a pro-apoptotic effect of lornoxicam on camel leukocytes, (4) Conclusions: Lornoxicam administration, at the dose and intervals utilized herein, induces significant changes in the phenotype and function of camel blood leukocytes. The reduced cell numbers of all studied leukocyte subpopulations in lornoxicam-treated camels, which seems to be a result of enhanced cell apoptosis, indicates an inhibitory effect rather than a modulatory effect of lornoxicam on the camel immune system, which need to be considered when using lornoxicam in camel medicine.

Objective: To develop and validate a novel, specific, precise and simple UV-spectrophotometric method for the estimation of lornoxicam present in microsponges. Lornoxicam is a non-steroidal anti-inflammatory drug(NSAID) of the oxicam class with analgesic(pain relieving), anti-inflammatory and antipyretic(fever reducing) properties. Methods: UV-spectrophotometric determination was performed with Thermo Scientific Evolution 201 UV-Vis spectrophotometer using methanol as a medium. The spectrum of the standard solution was run from 200-400 nm range for the determination of absorption maximum (λ max). λ max of lornoxicam was found at 353 nm. The absorbance of standard solutions of 3, 6, 9, 12 and 15, µg/ml of drug solution was measured at an absorption maximum at 353 nm against the blank. Then a graph was plotted by taking concentration on X-axis and absorbance on Y-axis which gave a straight line. Validation parameters such as linearity and range, selectivity and specificity, LOD and LOQ, accuracy, precision and robustness were evaluated as per ICH guidelines. Results: Linearity for the UV-spectrophotometric method was noted over a concentration range of 3.0-15.0 µg/ml with a correlation coefficient of 0.9995. The limit of detection (LOD) and limit of quantification (LOQ) for lornoxicam was found at 1.26 μg/ml and 3.82 μg/ml respectively. Accuracy was in between 99.21 and 99.60%. % RSD for repeatability, intraday precision and interday precision were found to be 0.473, in between 0.478 and 0.619 and in between 0.855 and 1.818 respectively. The proposed UV method is found to be robust. Conclusion: The proposed UV-Visible spectrophotometric method was validated according to the ICH guidelines and results and statistical parameters demonstrated that the developed method is sensitive, precise, reliable and simple for the estimation of lornoxicam present in microsponges.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of a variety of musculoskeletal conditions, injuries and after surgery for postoperative pain management. Their use has been associated with impaired bone healing, possibly due to a multifactorial function, which may include inhibition of osteoblast recruitment and differentiation. However, up to date, there is no consensus regarding the impact of NSAIDs on bone-healing. The aim of the current study was to investigate the effects of five NSAIDs on the cellular functions of mouse MC3T3-E1 pre-osteoblasts. Cells were treated with the non-selective COX inhibitors lornoxicam and diclofenac, the COX-2 selective inhibitors parecoxib, meloxicam and paracetamol, as well as steroidal prednisolone at different doses and exposure times. The PrestoBlue™ technique was used to measure cell viability, an enzymatic assay was employed for alkaline phosphatase (ALP) activity and alizarin red S mineral staining was used to determine osteogenic differentiation. All drugs had a negative impact on pre-osteoblast cell growth, with the exception of paracetamol. Lornoxicam, diclofenac and meloxicam reduced ALP activity, while the other NSAIDs had no effect and prednisolone strongly increased ALP activity. In contrast, calcium deposits were either unaffected or increased by NSAID treatments but were significantly decreased by prednisolone. These results provide evidence that NSAIDs may adversely affect the viability of mouse pre-osteoblast cells but their actions on the osteogenic differentiation are drug-specific. The direct comparison of the effects of different NSAIDs and prednisolone on pre-osteoblasts may serve to place some NSAIDs in a preferential position for analgesic and anti-inflammatory therapy during bone repair.

Purpose The goal of this research was to enhance the transdermal delivery of lornoxicam (LX), using nanovesicular carriers composed of the bile salt sodium deoxycholate (SDC), soybean phosphatidyl choline (SPC) and a permeation enhancer limonene. Methods Thin-film hydration was the technique employed for the fabrication using a Box–Behnken design with three central points. The investigated factors were SPC molar concentration, SDC amount in mg and limonene percentage (%). The studied responses were percent entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro drug release (after 2, 10 h). In order to obtain the optimum formula, numerical optimization by Design-Expert® software was used. Electing the optimized bilosomal formula was based on boosting %EE, ZP (as absolute value) and in vitro drug release, taking in consideration diminishing PS and PDI. Further assessment of the selected formula was achieved by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), stability testing, ex vivo skin permeation and deposition. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and compared to that of the oral market product. Results The optimized bilosomal formula demonstrated to be nonirritant, with noticeably enhanced anti-inflammatory and antinociceptive activities. Superior in vivo permeation was proved by confocal laser scanning microscopy (CLSM). Conclusion The outcomes demonstrated that bilosomes could improve transdermal delivery of lornoxicam., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/G8p7XhM43Og

In this work, an oxicam group-selective monoclonal antibody against 6 nonsteroidal anti-inflammatory drugs (NSAID; meloxicam, lornoxicam, piroxicam, sudoxicam, droxicam, and tenoxicam) was prepared. Also, a spacer arm with carboxyl group was derived at the hydroxyl of meloxicam to generate the meloxicam hapten. The half-maximal inhibitory concentrations (IC50) were, respectively, 0.31 ng/mL for meloxicam, 0.49 ng/mL for lornoxicam, 2.90 ng/mL for piroxicam, 1.95 ng/mL for sudoxicam, 3.08 ng/mL for droxicam, and 5.36 ng/mL for tenoxicam. A colloidal gold immunochromatographic strip based on the monoclonal antibody was developed for the detection of these 6 NSAID in milk. The results could be obtained by the naked eye in 10 min, and the cut-off values and the visual limits of detection in real samples were 5, 5, 10, 10, 25, and 25 ng/mL, and 0.25, 1, 0.5, 0.5, 1, and 1 ng/mL, respectively. This immunochromatopgraphic strip is a suitable tool for on-site detection and screening of oxicam NSAID in milk samples.

The lornoxicam (LRX) and tenoxicam (TNX) drugs form a stable 1:1 inclusion complex with b-cyclodextrin (β-CD) in aqueous solution. The experimentally determined association constants (K) of LRX- β-CD and TNX- β-CD are 13.4 and 10.3 M-1, respectively. Quantum chemical computations simulated the preferred orientation of guest molecules in the host. Geometry optimized results using the ONIOM technique provided more in-depth insights and identified the structure and showed that both drugs were partially encapsulated within the β-CD cavity. The calculated inclusion binding energy (BE, kcal mol-1) reveals the noticeable thermal stability of LRX-β-CD (-24.19 kcal/mol) over the TNX-β-CD (-13.45 kcal/mol) capsulate. Furthermore, the photostabilities of the encapsulated drugs were tested. Drug encapsulation did not result in any additional photostability. Moreover, encapsulation of the drugs in the β-CD resulted in noticeable changes in the electronic characteristics of the drugs, as reflected in their reactivity indices. The fact that the water-soluble β-CD formed inclusion complexes with water-insoluble LRX and TNX enables the drug delivery vehicle for oral administration.

To compare the efficacy, safety and tolerability of lornoxicam and xefocam used as the reference drug in patients with acute nonspecific pain in lower back caused by acute sciatica.A simple blind clinical study was conducted with 108 patients (men and women, aged 20-55 years) with complaints of pain in the lower back and an established diagnosis of vertebrogenic radiculopathy L4, L5, S1. Patients were randomized into 2 treatment groups by randomization method of envelopes in the ratio of 1:1 (54 patients per group). The first group received lornoxicam in a dose of 16 mg/day for 2 days, the second group was treated with xefocam (the lyophilisate for preparation of solution for intravenous and intramuscular injection) according to a similar scheme.The results demonstrate the comparable efficacy of lornoxicam and the reference drug. The analysis of the safety profile reveals no significant differences between treatment groups.Изучение эффективности, безопасности и переносимости воспроизведенного лорноксикама в сравнении с оригинальным препаратом ксефокам у пациентов с острой неспецифической болью в нижней части спины.Проведено простое слепое клиническое исследование с участием 108 пациентов (мужчин и женщин в возрасте 20—55 лет) с жалобами на боль в нижней части спины и установленным диагнозом вертеброгенной радикулопатии LПолученные результаты оценки эффективности показали не меньшую эффективность воспроизведенного препарата в сравнении с оригинальным препаратом. Анализ данных безопасности не выявил статистически значимых различий между группами лечения.

OBJECTIVE: Clinical utility of lornoxicam in oral therapy is primarily restricted by the low solubility and gastric adverse effects. This study evaluated the prospective of optimized proniosomal gel to improve the clinical efficacy of lornoxicam and compare with oral therapy. METHODS: Proniosomes were formulated by coacervation phase separation technique using span 60, lecithin and cholesterol. A four-factor three-level Box-Behnken design was used to evaluate the effect of amount of four independent variables; span 60 (X(1)), cholesterol (X(2)), lecithin (X(3)) and lornoxicam (X(4)) on response variables; vesicle size (Y(1)), entrapment efficiency (Y(2)) and transdermal flux (Y(3)). The selected proniosomal gel (F19) was characterized, and evaluated for the transdermal efficacy by ex vivo and in vivo experiments. RESULTS: Optimization study signifies that amount of formulation components (span 60, cholesterol, lecithin and lornoxicam) influence the vesicle size, entrapment efficiency and/or transdermal flux. Optimized formulation F19 exhibited nano size with high entrapment efficiency, adequate zeta potential, greater transdermal flux and better stability (at refrigerated conditions). The entrapment of lornoxicam in the bilayers of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F19 was distinct (p

The review presents current information on the role of NSAIDs in the development of cardiovascular disasters. The development of non-desirable cardiovascular effects and an increase in cardiovascular risk with the administration of NSAIDs, most experts assess in terms of the antagonistic effect on the platelet-vascular homeostasis of metabolites of COX-thromboxane A2 and prostaglandin I2 (prostacyclin). All the presented reviews confirming an increase in the risk of MI complications in the administration of NSAIDs, indicate the class-specificity of this undesirable effect, not homogeneous for different representatives of the group. Important clinical aspects of prescribing NSAIDs for patients with low and moderate cardiovascular risk are the clinical features of the patient and the individual set of risk factors for CVD. Such pharmacokinetic characteristics of NSAIDs as a short half-life, a high degree of binding to blood plasma albumins are indicative of greater safety of NSAIDs, but the final decision must be made based on the accumulated data of clinical trials and meta-analyzes. Keywords: nonsteroidal anti-inflammatory drugs, cardiovascular diseases, cardiovascular risk, lornoxicam, diclofenac sodium, thrombo-elastogram, myocardial infarction, stroke.

Objective: The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. Methods: Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. Results: The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. Conclusion: Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.