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Saudi Pharmaceutical Journal : SPJ :... Apr 2021The study designed, formulated and evaluated meloxicam emulgels as a potential alternative topical treatment option for rheumatism.
PURPOSE
The study designed, formulated and evaluated meloxicam emulgels as a potential alternative topical treatment option for rheumatism.
METHODS
A 3 factorial design was employed to formulate nine preliminary meloxicam emulgels (Formulations F1 - F9). The influences of carbopol-934 and menthol as gelling agent and drug release enhancer, respectively, were correlated with four pharmaceutical properties of the formulated emulgels namely viscosity, spreadability, and cumulative drug release at one hour and at eight hours. Using the generated data and applying the Design Expert® modelling software, two optimized meloxicam emulgels (Formulations F10 and F11) were designed, formulated and evaluated. In vivo anti-inflammatory efficacy was conducted using carrageenan-induced rat paw oedema method. Drug release kinetics was modelled using DDSolver® dissolution software.
RESULTS
All formulations were homogenous with no observable grittiness or phase separation. The optimized Formulations F10 and F11 had pH 6.5 and 6.4, viscosity of 23656 and 24524 mPa.s, spreadability of 9.9 and 9.5 cm, and drug content of 90.4% and 92.9%, respectively, all within optimal values. The cumulative percentage of drug released was 21.0% and 22.9% after one hour and 50.1% and 55.8% after eight hours for Formulations F10 and F11, respectively. Drug release kinetics exhibited Fickian diffusion best described by Korsmeyer-Peppas model. Paw volume inhibition by Formulation F11 at two and three hours after carrageenan injection was statistically significant ( < 0.05).
CONCLUSION
The optimized meloxicam emulgels had high pharmaceutical quality and were pharmacologically active. Further optimization could potentially provide a safe and efficacious alternative treatment option for rheumatism.
PubMed: 33994830
DOI: 10.1016/j.jsps.2021.03.005 -
Arabian Journal For Science and... 2022Drug development on basis of coordination compounds provides versatile structural and functional properties as compared to other organic compounds. In the present study,...
Drug development on basis of coordination compounds provides versatile structural and functional properties as compared to other organic compounds. In the present study, a new Ca(II) complex of meloxicam was synthesized and characterized by elemental analysis, FT-IR, UV-Vis, C NMR, SEM-EDX, powder XRD and thermal analysis (TGA). The Ca(II) complex was investigated for its in vitro, in vivo biological activities and in silico docking analysis against COX-1 and COX-2. The spectral analysis indicates that the meloxicam acts as a deprotonated bidentate ligand (coordinated to the metal atom through the amide oxygen and the nitrogen atom of the thiazolyl ring) in the complex. SEM-EDX and powder XRD analysis depicted crystalline morphology of Ca(II) complex with a crystalline size of 32.86 nm. The in vitro biological activities were evaluated by five different antioxidant methods and COX inhibition assay, while in vivo activities were evaluated by carrageenan-, histamine- and PGE-induced paw edema methods and acetic acid-induced writhing test. The Ca(II) complex showed prominent antioxidant activities and was found to be more selective toward COX-2 (43.77) than COX-1 as compared to meloxicam. It exhibited lower toxicity (LD 1000 mg/Kg) and significantly inhibited carrageenan- and PGE-induced inflammation at 10 mg/Kg ( < 0.05), but no significant effect was observed on histamine-induced inflammation. Moreover, Ca(II) complex significantly reduced the number of writhes induced by acetic acid ( < 0.05). The in silico molecular docking data revealed that Ca(II) complex obstructed COX-2 (dock score 6438) more effectively than COX-1 (dock score 5732) as compared to meloxicam alone.
PubMed: 35070636
DOI: 10.1007/s13369-021-06521-7 -
Journal of Feline Medicine and Surgery Mar 2023This study compared an opioid-free injectable anaesthetic protocol with or without multimodal analgesia in kittens undergoing ovariohysterectomy.
OBJECTIVES
This study compared an opioid-free injectable anaesthetic protocol with or without multimodal analgesia in kittens undergoing ovariohysterectomy.
METHODS
In this prospective, randomised, blinded, clinical trial, 29 healthy kittens (mean ± SD weight 1.55 ± 0.46 kg; aged 10 weeks to 6 months) were included. Anaesthesia was performed with an intramuscular injection of ketamine (4 mg/kg), dexmedetomidine (40 μg/kg) and midazolam (0.25 mg/kg). In the multimodal group (MMG), cats (n = 14) received meloxicam (0.1 mg/kg SC) and intraperitoneal bupivacaine 0.25% (2 mg/kg), whereas the same volume of saline was administered in the control group (CG; n = 15). Atipamezole (0.4 mg/kg IM) was given 15 mins after ovariohysterectomy. Postoperative pain was assessed using the UNESP-Botucatu multidimensional feline pain assessment scale - short form. Rescue analgesia (buprenorphine 0.02 mg/kg IM in MMG/CG and meloxicam 0.1 mg/kg SC in CG) was administered if pain scores were ⩾4/12. Soft food intake (after 2 and 60 mins) was evaluated at specific time points postoperatively. Statistical analyses were performed with linear models and post-hoc pairwise comparison with Benjamini-Hochberg corrections ( <0.05).
RESULTS
The prevalence of rescue analgesia was higher in the CG (n = 15/15) than the MMG (n = 1/14; <0.001). Pain scores at 1 h, 2 h and 4 h postoperatively were higher in the CG (4.1 ± 2.8, 4.8 ± 3.0 and 5.3 ± 1.2, respectively) than in the MMG (1.6 ± 1.0, 1.1 ± 1.0 and 0.9 ± 0.8, respectively; <0.001). Food intake (%) at 1 h postoperatively was higher in the MMG after 2 and 60 mins (10.4 ± 9 and 71.9 ± 29, respectively) than in the CG (1.4 ± 2 and 13.9 ± 7, respectively; <0.001).
CONCLUSIONS AND RELEVANCE
This opioid-free protocol using multimodal analgesia produced adequate postoperative pain relief, while almost eliminating the need for rescue analgesia in kittens undergoing ovariohysterectomy. Pain decreased food intake.
Topics: Hysterectomy; Ovariectomy; Single-Blind Method; Animals; Cats; Female; Anesthesia; Analgesics, Opioid; Ketamine; Dexmedetomidine; Midazolam; Meloxicam; Bupivacaine; Pain, Postoperative; Eating; Injections, Intramuscular; Pain Measurement
PubMed: 36943182
DOI: 10.1177/1098612X231158582 -
Pharmaceutics Jun 2021The interaction between meloxicam and sulfonatocalix [4] naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility...
The interaction between meloxicam and sulfonatocalix [4] naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix [4] naphthalene. The solubility phase diagram was classified as A type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix [4] naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release ( ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR in the investigated media, with average values ranging from 5.4-65.28 folds and 7.3-90.7, respectively. In conclusion, sulfonatocalix [4] naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.
PubMed: 34209201
DOI: 10.3390/pharmaceutics13070994 -
Animals : An Open Access Journal From... Feb 2022The analgesic efficacy of meloxicam and ketoprofen against equine visceral pain is unclear. The aim of this study was to compare the analgesic efficacy of meloxicam (M)...
The analgesic efficacy of meloxicam and ketoprofen against equine visceral pain is unclear. The aim of this study was to compare the analgesic efficacy of meloxicam (M) and ketoprofen (K) to flunixin meglumine (F) following inguinal castration. Horses undergoing inguinal castration under general anesthesia were randomly assigned F (1.1 mg/kg), M (0.6 mg/kg) or K (2.2 mg/kg) intravenously two hours pre-operatively and 24 h later. A pain score (out of 31) was recorded blindly by a senior clinician and veterinary student before NSAIDs administration (T), and after the first (T) and second (T) administrations, using a modified post-abdominal surgery pain assessment scale (PASPAS). Pain was classified as mild (score ≤ 7), moderate (score = 8-14) or severe (score > 14). Thirty horses (12 F, 10 M, 8 K) aged 6.2 ± 4.9 years, mostly warmbloods, were included. Horse welfare was not compromised regardless of the drug assigned. There was no statistically significant effect of NSAIDs on pain score. Mean pain scores were significantly higher at T than T for each NSAID (F: 5.08 ± 2.50 vs. 1.58 ± 1.38 ( < 0.001); M: 4.60 ± 2.32 vs. 1.10 ± 1.20 ( < 0.001); K: 5.25 ± 1.39 vs. 1.50 ± 1.51 ( < 0.0001)) and lower at T than T for F (2.92 ± 2.423 vs. 5.08 ± 2.50 ( < 0.001)) and M (2.90 ± 1.37 vs. 4.60 ± 2.32 ( < 0.0325)). At T, senior pain scores were significantly different than for junior (5.56 ± 0.54 vs. 3.22 ± 0.62, = 0.005). This study indicates that meloxicam and ketoprofen provide a similar level of analgesia to flunixin meglumine for the management of mild visceral pain in horses. PASPAS is not reliable for junior evaluators.
PubMed: 35203234
DOI: 10.3390/ani12040526 -
JAMA Internal Medicine Sep 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects.
OBJECTIVE
To evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis.
DESIGN, SETTING, AND PARTICIPANTS
The Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis.
INTERVENTIONS
Participants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2).
MAIN OUTCOMES AND MEASURES
The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks.
RESULTS
A total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, -0.2; 95% CI, -0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, -1.4 to 3.2; P = .45) between the 2 groups after 14 weeks.
CONCLUSIONS AND RELEVANCE
Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants' global impression of change or function after 14 weeks.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01799213.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cognitive Behavioral Therapy; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Telemedicine; Treatment Outcome
PubMed: 32702101
DOI: 10.1001/jamainternmed.2020.2821 -
Membranes Apr 2023The purpose of the present paper was to assess the ability of five newly designed and synthesized meloxicam analogues to interact with phospholipid bilayers....
The purpose of the present paper was to assess the ability of five newly designed and synthesized meloxicam analogues to interact with phospholipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of the chemical structure, the studied compounds penetrated bilayers and affected mainly their polar/apolar regions, closer to the surface of the model membrane. The influence of meloxicam analogues on the thermotropic properties of DPPC bilayers was clearly visible because these compounds reduced the temperature and cooperativity of the main phospholipid phase transition. Additionally, the studied compounds quenched the fluorescence of prodan to a higher extent than laurdan, what pointed to a more pronounced interaction with membrane segments close to its surface. We presume that a more pronounced intercalation of the studied compounds into the phospholipid bilayer may be related to the presence of the molecule of a two-carbon aliphatic linker with a carbonyl group and fluorine substituent/trifluoromethyl group (compounds and ) or the three-carbon linker together with the trifluoromethyl group (). Moreover, computational investigations of the ADMET properties have shown that the new meloxicam analogues are characterized by beneficial expected physicochemical parameters, so we may presume that they will have a good bioavailability after an oral administration.
PubMed: 37103843
DOI: 10.3390/membranes13040416 -
Veterinary Anaesthesia and Analgesia Jul 2022To investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus).
OBJECTIVE
To investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus).
STUDY DESIGN
A crossover design with an 11 day washout period.
ANIMALS
A total of eight young male reindeer, aged 1.5-2.5 years and weighing 74.3 ± 6.3 kg, mean ± standard deviation.
METHODS
The reindeer were administered meloxicam (0.5 mg kg IV or orally). Blood samples were repeatedly collected from the jugular vein for up to 72 hours post administration. Plasma samples were analysed for meloxicam concentrations with ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry. Noncompartmental analysis for determination of pharmacokinetic variables was performed.
RESULTS
The pharmacokinetic values, median (range), were determined. Elimination half-life (t) with the IV route (n = 4) was 15.2 (13.2-16.8) hours, the volume of distribution at steady state was 133 (113-151) mL kg and clearance was 3.98 (2.63-5.29) mL hour kg. After oral administration (n = 7), the peak plasma concentration (C) was detected at 6 hours, t was 19.3 (16.7-20.5) hours, C 1.82 (1.17-2.78) μg mL and bioavailability (n = 3) 49 (46-73)%. No evident adverse effects were detected after either administration route.
CONCLUSIONS AND CLINICAL RELEVANCE
A single dose of meloxicam (0.5 mg kg IV or orally) has the potential to maintain the therapeutic concentration determined in other species for up to 3 days in reindeer plasma.
Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Half-Life; Male; Meloxicam; Reindeer
PubMed: 35659721
DOI: 10.1016/j.vaa.2022.04.005 -
Polymers Oct 2022This study proposes a simple and effective method to obtain ultra-thin membranes based on κ-carrageenan. Two types of membranes were obtained, one based on...
This study proposes a simple and effective method to obtain ultra-thin membranes based on κ-carrageenan. Two types of membranes were obtained, one based on κ-carrageenan and the second type based on κ-carrageenan, hydroxyethyl cellulose and the plasticizer (glycerol). Three non-steroidal anti-inflammatory drugs (Dexketoprofen trometamol, Meloxicam, Diclofenac sodium) and a glucocorticoid (Dexamethasone) were introduced, looking for the best option for incorporation. The obtained membranes were characterized by FTIR, TG/DTG and UV-VIS methods and the data collected following these methods indicated success in terms of the incorporation of the active substance, as well as the high thermal stability in the temperature range 37-100 °C of both the matrices of membrane types, as well as the membranes with the drug incorporated. All the studies carried out led to the conclusion that within all the membranes the anti-inflammatory substances were intact and, thus we can say that these membranes can be used for transdermal administration of the studied anti-inflammatory substances.
PubMed: 36297853
DOI: 10.3390/polym14204275 -
Evidence-based Complementary and... 2021The high prevalence of knee osteoarthritis (KOA) is a major cause of disability among elders. NSAIDs are recommended to reduce KOA patients' symptoms, but their adverse...
PURPOSE
The high prevalence of knee osteoarthritis (KOA) is a major cause of disability among elders. NSAIDs are recommended to reduce KOA patients' symptoms, but their adverse side effects limit their consumption. In this study, we evaluated the effectiveness of compared to a routine NSAID (meloxicam) on pain reduction and functional improvement of KOA patients. . Sixty patients aged 40-60 years, with painful knee osteoarthritis (grades 1-2 of Kellgren-Lawrence scale) for at least one month, were randomized into two groups with different routine medication periods. Group A consisted of daily administration of two (Teltonal) tablets (2480 mg) for one month, and group B consisted of daily administration of meloxicam (15 mg) for ten days. The visual analogue scale (VAS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), Oxford Knee Scale (OKS), and patient satisfaction were evaluated at the baseline and after 2, 4, and 8 weeks.
RESULTS
There were no statistically significant differences between demographic characteristics, pain intensity, and function scores before the treatment. VAS, OKS, and WOMAC scores improved in both groups ( < 0.001) over time, but no significant superiority was shown; after 8 weeks: VAS (Teltonal (4.80 ± 1.80) vs. meloxicam (5.06 ± 1.43)), OKS (34.06 ± 4.38, 34.00 ± 7.87, Teltonal vs. meloxicam, respectively), and WOMAC scores (25.73 ± 10.11 Teltonal vs. 26.20 ± 13.94, meloxicam).
CONCLUSION
Teltonal is an effective and safe treatment in patients with mild KOA in the short term. However, no significant superiority was shown in using Teltonal or meloxicam, in people who cannot take NSAIDs, it can be a good alternative, although difference in medication periods should be considered.
PubMed: 34712343
DOI: 10.1155/2021/5596892