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Background: Despite the fact that thiocolchicoside has been widely used in the treatment of musculoskeletal pain, its efficacy has never been systematically evaluated. We carried out a systematic review and meta-analysis of randomized clinical trials (RCTs) to appraise the existing evidence on the efficacy of thiocolchicoside for musculoskeletal pain management. Methods: The literature search was performed on multiple databases, extracting reports of RCTs evaluating the efficacy of thiocolchicoside compared to placebo or no exposure. The reduction in pain intensity was evaluated through between-groups mean differences (MDs) in Visual Analogue Scale (VAS) scores after the intervention. The pooled effect estimates were compared to a minimally important difference (MID) of 1 point on a scale from 0 to 10. Results: We retrieved eight RCTs, including a total of 1397 patients. All the included studies were determined as being at high risk of bias. Seven trials evaluated patients with acute low back pain. After 2–3 days of treatment, the pooled MD in VAS score was −0.49 (95%CI = −0.90; −0.09) compared to controls. After 5–7 days of treatment, the summary MD was −0.82 (95%CI = −1.46; −0.18). Conclusions: Although thiocolchicoside was found to significantly reduce patient-reported low back pain, the clinical impact was very small, as the pooled effect estimates were below the MID, and the overall certainty of evidence was very low. In light of the safety concerns raised by the European Medicine Agency, an in-depth analysis on the risk–benefit balance of thiocolchicoside is required. [ABSTRACT FROM AUTHOR]

Background: Lower backache is a highly prevalent condition among middle-aged individuals and is often caused by muscle spasms. It is one of the most common reasons why people seek medical assistance from a primary care physician. Aims and Objectives: The aims and objectives of the study are to evaluate the safety and efficacy of the drug combinations thiocolchicoside 4 mg and aceclofenac 100 mg versus aceclofenac 100 mg and paracetamol 500 mg. Materials and Methods: The study was conducted using a prospective, randomized, double-blind, comparative, and parallel group design. A total of 80 patients who met the specified criteria were selected to participate in the trial over a period of 3 months. A total of 30 cases were selected for each group, with consideration given to excluding outliers. The patients were allocated randomly into two groups: Group A, consisting of 30 individuals, and Group B, consisting of 30 individuals. The primary efficacy assessments include the visual analog scale, muscle spasm assessment by finger-to-floor distance, and Lasegue's maneuver. The secondary efficacy measures were assessed using a 4-point scale global assessment, which included ratings of excellent, good, average, and poor. Results: The majority of study participants were in the age group 39-48 years and above 48 years consisting of 25 patients and 33, respectively. Males constituted 51.6% and females were 48.3%. On day 28, results were calculated on 26 patients in Group A and 24 patients in Group B as 10 patients discontinued the treatment after 3rd week. Conclusions: It is concluded that the best possible medical intervention to treat acute low back pain is to use drug combinations of analgesics and skeletal muscle relaxants. The combination of tablet thiocolchicoside and aceclofenac proved to be more efficacious and safer when compared to the combination of tablet aceclofenac and paracetamol. [ABSTRACT FROM AUTHOR]

Recently, drug release applications through the skin have become very popular. One of the most remarkable of these drug release applications is transdermal drug release systems, which are drug release methods that allow the active substance to pass into the systemic circulation through the skin or artificial membranes. In this study, the optimization conditions required for the release and permeation tests of a gel drug containing the active substance thiocolchicoside were comparatively investigated using synthetic membranes without human or animal skin. For this purpose, the permeability of the gel drug in gel form and the active ingredient thiocolchicoside was carried out using Franz Diffusion Cell. As a result of the investigations, it was observed that the best synthetic membrane for the permeability of thiocolchicoside in the Franz Diffusion Cell was the Supor membrane. In addition, the method's relative standard deviation values, detection, and quantification limits were determined, and permeation studies were carried out. In this study, the correlation coefficient was found to be 0.9992, and the limits of detection and quantification were 0.026 and 0.078 µg/L. In this way, the sensitivity and reliability of the validation study were determined. [ABSTRACT FROM AUTHOR]

Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared. Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as Cmax, Tmax, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties. Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula. In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells. [ABSTRACT FROM AUTHOR]

This study aimed to formulate nano-cubosomes (NCs) co-loaded with capsaicin (CAP) and thiocolchicoside (TCS) to enhance their bioavailability and minimize associated potential side effects through transdermal delivery alongside their synergistic activity. Twenty seven (27) nano-cubosomal dispersions were prepared according to Box-Behnken factorial design and the effect of CAP, TCS, glyceryl mono oleate (GMO) and poloxamer 407 (P407) concentrations on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were assessed. The results revealed that the optimized formulation exhibited a mean droplet size of 503 ± 10.3 nm, PDI of 0.405 ± 0.02, zeta potential of −10.0 ± 1.70 mV and entrapment efficiency of 86.9 ± 3.56 %. The in vivo anti-inflammatory effect of optimized formulation was studied in rats by injecting carrageenan to induce edema. The results of in vivo study showed that transdermal application of nano-cubosomes co-loaded with CAP and TCS significantly (p value

Background: Thiocolchicoside and chlorzoxazone are commonly used muscle relaxants for the management of acute musculoskeletal pain. However, there is limited evidence comparing their efficacy and safety. Aims and Objectives: The aim of the study was to compare the efficacy and safety of thiocolchicoside and chlorzoxazone in patients with acute musculoskeletal pain. Materials and Methods: This was a randomized, open-label, parallel-group study conducted in a tertiary care hospital. A total of 50 patients with acute musculoskeletal pain were randomized to receive either thiocolchicoside (8 mg) or chlorzoxazone (500 mg) thrice daily for 7 days. The primary outcome measure was the change in pain intensity from baseline to Day 7, assessed using a visual analog scale (VAS). The secondary outcome measures were the percentage reduction in pain intensity and the incidence of adverse events. Results: The baseline characteristics of the patients were similar in both groups. The mean baseline pain intensity was 7.2±1.3 in the thiocolchicoside group and 7.1±1.2 in the chlorzoxazone group. After 7 days of treatment, both drugs significantly reduced pain intensity from baseline. The mean pain intensity at Day 7 was 2.9±1.1 in the thiocolchicoside group and 3.1±1.2 in the chlorzoxazone group. The percentage reduction in pain intensity was 59.7%±12.3% in the thiocolchicoside group and 56.3%±11.5% in the chlorzoxazone group. However, there was no statistically significant difference between the groups in terms of pain intensity reduction (P=0.453). Conclusion: The results of this study suggest that thiocolchicoside and chlorzoxazone are equally effective and safe in the management of acute musculoskeletal pain. The choice of drug may depend on the patient’s individual characteristics and risk factors.

Purpose: The risk minimization measures (RMM) for systemic use of thiocolchicoside (TCC) was implemented across Europe during 2014–2016. RMM included restriction of use in age <16 years, maximum dose and duration, chronic conditions, contraindication in pregnancy, lactation or in women of childbearing potential [WOCBP] without appropriate contraception. The current Drug Utilization Study was aimed to describe the prescribing practices of TCC in France and Italy. Method: The study analyzed data (demographic, prescription, diagnosis, and concomitant treatment) from electronic medical record databases. It compares drug utilization during pre‐implementation (baseline: year 2013) and post‐implementation (years 1, 2, and 3) of RMM. This study included panels of general practitioners (FGP) and rheumatologists (FRH) in France and Italy (IGP). Results: TCC was largely prescribed as adjuvant therapy in both pre‐implementation (FGP: 93.5%, FRH: 88.8%, IGP: 86.6%) and post‐implementation (FGP: 92.3%, FRH: 89.5%, IGP: 89.0%) periods. Prescribing patterns were different in France and Italy, with FGP and FRH mainly prescribing oral formulation (>95% and >80%, respectively), while IGP prescribing intramuscular formulation (>70%). Prescriptions to patients aged ≥16 years were >99% in all panels during both periods. An improvement was observed in compliance with treatment duration for oral formulation in the FGP panel post‐implementation versus pre‐implementation (66.2% vs. 46.7%; p < 0.001). There was no change in prescription rate post RMM implementation in pregnant (FGP: 0.5%, IGP: 4.7%) and in WOCBP without appropriate contraception (FGP: 89.3%, IGP: 93.4%). Conclusion: These results highlighted changes in prescribing practices of TCC after RMM implementation, which varied across panels and measures. [ABSTRACT FROM AUTHOR]

Objective: The combination of the non-steroidal anti-inflammatory drug dexketoprofen trometamol (DXT) and the centrally acting muscle relaxant thiocolchicoside (TH) is used for symptomatic relief in various conditions, with the aim of alleviating associated symptoms. The study involves the development, validation, and application of the chemometrics-based spectrophotometric method. Methods: An integral aspect of the investigation is the strategic application of experimental design techniques for calibration and validation mixtures to facilitate the assessment of factor effects within complex matrices. In this study, a factorial design was used to prepare calibration (25 samples) and validation (8 samples) sets comprising mixtures of DXT and TH within their linear ranges (2.5-25 µg/mL for DXT and 2-16 µg/mL for TH). Results: Spectra of the acquired mixtures and samples were recorded at wavelengths between 220nm and 460 nm at Δλ = 1 nm intervals. Using regression models based on the principal component regression algorithm, the results obtained showed satisfactory performance, with a recovery rate of =98.54% for DXT and =98.88% for TH. Conclusion: These models offer the potential for accurate identification and quantification of DXT and TH in pharmaceutical preparations. [ABSTRACT FROM AUTHOR]

Abstract Background Non-specific acute low back pain (LBP) is a common health problem that may be accompanied by muscle spasm and decreased mobility. The combination of non-steroidal anti-inflammatory drugs and muscle relaxants represents an advantageous therapeutic option, however, available data on their combined use are conflicting. This prospective, randomized, single-blind, two-parallel-group trial assessed the efficacy of a single intramuscular (IM) injection of the fixed-dose combination (FDC) diclofenac (75 mg)-thiocolchicoside (4 mg/4 ml) product (test treatment) compared to diclofenac (75 mg/3 ml) alone (reference treatment) for the symptomatic relief of acute LBP. Tolerability and safety were also assessed as secondary variables. Methods One hundred thirty-four patients were enrolled (safety population) and randomly allocated to the combination or single-agent regimen. Pain intensity and muscle spasm, assessed respectively by the patient-reported visual analogue scale and investigator-performed finger-to-floor distance test, were determined prior to the injection as well as 1 and 3 h post-injection in 123 patients (per-protocol population). The patients were blinded to treatment. Safety was assessed up to 24 h post-injection. Results The test treatment was superior in both alleviating the pain intensity and reducing the finger-to-floor distance at both 1 (p 30% reduction in pain intensity at 1 and 3 h with the test treatment (p = 0.037 and p

Background: Thiocolchicoside and chlorzoxazone are commonly used muscle relaxants for the management of acute musculoskeletal pain. However, there is limited evidence comparing their efficacy and safety. Aims and Objectives: The aim of the study was to compare the efficacy and safety of thiocolchicoside and chlorzoxazone in patients with acute musculoskeletal pain. Materials and Methods: This was a randomized, open-label, parallel-group study conducted in a tertiary care hospital. A total of 50 patients with acute musculoskeletal pain were randomized to receive either thiocolchicoside (8 mg) or chlorzoxazone (500 mg) thrice daily for 7 days. The primary outcome measure was the change in pain intensity from baseline to Day 7, assessed using a visual analog scale (VAS). The secondary outcome measures were the percentage reduction in pain intensity and the incidence of adverse events. Results: The baseline characteristics of the patients were similar in both groups. The mean baseline pain intensity was 7.2±1.3 in the thiocolchicoside group and 7.1±1.2 in the chlorzoxazone group. After 7 days of treatment, both drugs significantly reduced pain intensity from baseline. The mean pain intensity at Day 7 was 2.9±1.1 in the thiocolchicoside group and 3.1±1.2 in the chlorzoxazone group. The percentage reduction in pain intensity was 59.7%±12.3% in the thiocolchicoside group and 56.3%±11.5% in the chlorzoxazone group. However, there was no statistically significant difference between the groups in terms of pain intensity reduction (P=0.453). Conclusion: The results of this study suggest that thiocolchicoside and chlorzoxazone are equally effective and safe in the management of acute musculoskeletal pain. The choice of drug may depend on the patient's individual characteristics and risk factors. [ABSTRACT FROM AUTHOR]

Background: Non-specific acute low back pain (LBP) is a common health problem that may be accompanied by muscle spasm and decreased mobility. The combination of non-steroidal anti-inflammatory drugs and muscle relaxants represents an advantageous therapeutic option, however, available data on their combined use are conflicting. This prospective, randomized, single-blind, two-parallel-group trial assessed the efficacy of a single intramuscular (IM) injection of the fixed-dose combination (FDC) diclofenac (75 mg)-thiocolchicoside (4 mg/4 ml) product (test treatment) compared to diclofenac (75 mg/3 ml) alone (reference treatment) for the symptomatic relief of acute LBP. Tolerability and safety were also assessed as secondary variables. Methods: One hundred thirty-four patients were enrolled (safety population) and randomly allocated to the combination or single-agent regimen. Pain intensity and muscle spasm, assessed respectively by the patient-reported visual analogue scale and investigator-performed finger-to-floor distance test, were determined prior to the injection as well as 1 and 3 h post-injection in 123 patients (per-protocol population). The patients were blinded to treatment. Safety was assessed up to 24 h post-injection. Results: The test treatment was superior in both alleviating the pain intensity and reducing the finger-to-floor distance at both 1 (p < 0.01 and p = 0.023 respectively) and 3 h post-injection (p < 0.01). A higher percentage of patients experienced > 30% reduction in pain intensity at 1 and 3 h with the test treatment (p = 0.037 and p < 0.01 respectively). The corresponding VAS (SD) scores for the test treatment group were at baseline, 1 and 3 h post-injection 72.03 (± 11.72), 45.37 (± 16.28) and 31.56 (± 15.08) respectively and for the reference treatment group 65.20 (± 12.16), 48.98 (± 18.76) and 44.52 (± 17.33) respectively. No adverse effects were reported with the combination treatment, whereas two patients treated with diclofenac reported dizziness. Conclusions: The FDC treatment is an effective and well-tolerated option for the symptomatic treatment of LBP. Clinical and patient-reported assessments confirmed that a single IM injection of FDC diclofenac-thiocolchicoside was more effective than diclofenac alone in conferring rapid and sustained improvement in mobility and pain intensity. Trial registration: EudraCT No: 2017–004530-29 Available at https://eudract.ema.europa.eu/ Registered 04 Dec 2017. [ABSTRACT FROM AUTHOR]

White analytical chemistry is a novel concept for the assessment of analytical methods on basis of its validation efficiency, greenness power, and economical efficiency. White analytical chemistry‐driven stability indicating chromatographic method has been developed for the concomitant analysis of thiocolchicoside and aceclofenac. The proposed chromatographic method has been developed using a safe and environmental‐friendly organic solvents for the concomitant stability study of thiocolchicoside and aceclofenac. The analytical risk assessment was carried out for the identification of high‐risk analytical risk factors and analytical method performance attributes. The mixture design was applied for the design of experiments‐based response surface modeling of high‐risk analytical risk factors and analytical method performance attributes. The degradation products were isolated and characterized using infrared, nuclear magnetic resonance, and mass spectral data. The proposed method was compared for its validation efficiency, greenness power, and cost‐efficiency with published chromatographic methods using the red, green, and blue models. The white score of the proposed and reported method was calculated by averaging the red, green, and blue scores of the methods. The proposed method was found to be robust, green, and economical for the concomitant stability study of thiocolchicoside and aceclofenac. [ABSTRACT FROM AUTHOR]

The present study was conducted to fabricate and characterize mucilage-based polymeric networks of Aloe vera for controlled drug release. Aloe vera mucilage was used to develop a polymeric network via the free-radical polymerization method using potassium persulphate as the initiator, N′ N′-Methylene bisacrylamide as the crosslinker, and acrylamide as the monomer. Using varying concentrations of Aloe vera mucilage, crosslinker, and monomer, we developed different formulations. Swelling studies were conducted at pH 1.2 and 7.4. Concentrations of polymer, monomer, and crosslinker were optimized as a function of swelling. Porosity and gel content were calculated for all samples. FTIR, SEM, XRD, TGA, and DSC studies were conducted for the characterization of polymeric networks. Thiocolchicoside was used as a model drug to study the in vitro release in acidic and alkaline pH. Various kinetics models were applied by using a DD solver. Increasing content of monomer and crosslinker swelling, porosity, and drug release decreased while gel content increased. An increase in Aloe vera mucilage concentration promotes swelling, porosity, and drug release of the polymeric network but decreases gel content. The FTIR study confirmed the formation of crosslinked networks. SEM indicated that the polymeric network had a porous structure. DSC and XRD studies indicated the entrapment of drugs inside the polymeric networks in amorphous form. The analytical method was validated according to ICH guidelines in terms of linearity, range, LOD, LOQ, accuracy, precision, and robustness. Analysis of drug release mechanism revealed Fickian behavior of all formulations. All these results indicated that the M1 formulation was considered to be the best polymeric network formulation in terms of sustaining drug release patterns. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the efficacy and safety of thiocolchicoside (TCC) ointment treatment compared to placebo in patients with chronic mechanical low back pain (LBP) accompanied by acute muscle spasms. Patients and methods: A total of 292 adult patients (106 males, 186 females; mean age: 38.5±11.2 years; range, 18 to 64 years) were randomized to TCC group (n=147) and placebo group (n=145) in 12 centers between March 2020 and March 2021. Eight patients from each group were excluded from the analysis. The primary endpoint was pressure pain threshold (PPT) on Day 3, which was measured using a pressure algometer. Secondary endpoints were PPT on Day 7, patient, and physician Visual Analog Scales-pain (VAS-pain) on Days 3 and 7, and safety. Results: The PPT values on Day 3 was not significantly different between the treatment groups (p=0.701). Similarly, TCC and placebo group had similar VAS-pain scores over trial period (p=0.577 or higher for comparisons). Significantly higher PPT values and lower VAS-pain scores on Days 3 and 7 were observed in both groups (p<0.001 for all). In patients with a PPT value of =3.87, TCC arm had higher PPT on Day 3 compared to placebo (p=0.029). Three patients (two in the TCC arm and one in the placebo arm) discontinued the trial due to an adverse event. Conclusion: Topical TCC can be an appropriate option in a subset of patients with mild chronic LBP accompanied by muscle spasms. In a subset of patients with milder pain intensity, topical TCC may improve pain earlier. The results of this trial are compatible with the treatment approaches used in daily practice. [ABSTRACT FROM AUTHOR]

Objective: The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside., Material and Method: The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets., Result: Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm 2 . Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution., Conclusion: A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

TCC is a semisynthetic molecule widely used in clinical settings as a pain killer and myorelaxant. Several neurological side effects have been reported in association with TCC treatment including somnolence, confusion and seizure, the latter in a lower percentage of patients. Some previous reports described seizure onset after TCC intake in adulthood. However, major epileptological complication, namely status epilepticus, has never been previously reported in association with TCC treatment. In our report, we describe a case of acute refractory non‐convulsive status epilepticus (NCSE) in the context of a TCC‐induced acute toxic encephalopathy (ATE) in a woman without any previous neurological or physical comorbidities. [ABSTRACT FROM AUTHOR]

The present study was conducted to fabricate and characterize mucilage-based polymeric networks of Aloe vera for controlled drug release. Aloe vera mucilage was used to develop a polymeric network via the free-radical polymerization method using potassium persulphate as the initiator, N′ N′-Methylene bisacrylamide as the crosslinker, and acrylamide as the monomer. Using varying concentrations of Aloe vera mucilage, crosslinker, and monomer, we developed different formulations. Swelling studies were conducted at pH 1.2 and 7.4. Concentrations of polymer, monomer, and crosslinker were optimized as a function of swelling. Porosity and gel content were calculated for all samples. FTIR, SEM, XRD, TGA, and DSC studies were conducted for the characterization of polymeric networks. Thiocolchicoside was used as a model drug to study the in vitro release in acidic and alkaline pH. Various kinetics models were applied by using a DD solver. Increasing content of monomer and crosslinker swelling, porosity, and drug release decreased while gel content increased. An increase in Aloe vera mucilage concentration promotes swelling, porosity, and drug release of the polymeric network but decreases gel content. The FTIR study confirmed the formation of crosslinked networks. SEM indicated that the polymeric network had a porous structure. DSC and XRD studies indicated the entrapment of drugs inside the polymeric networks in amorphous form. The analytical method was validated according to ICH guidelines in terms of linearity, range, LOD, LOQ, accuracy, precision, and robustness. Analysis of drug release mechanism revealed Fickian behavior of all formulations. All these results indicated that the M1 formulation was considered to be the best polymeric network formulation in terms of sustaining drug release patterns.

The present study represents four simple UV spectrophotometric methods that are accurate, precise, and ecofriendly for estimating flupirtine maleate and thiocolchicoside in pharmaceutical formulation. The four methods are the second order derivative of zero order spectra, the first derivative of ratio spectra, the extended ratio subtraction technique, and the absorption factor method. The proposed methods have linear calibration curves in the range of 14-26 to 2.80-5.2 µg mL-1 for flupirtine maleate and thiocolchicoside, correspondingly. The proposed methods are evaluated toward synthetic mixtures of the drugs as mentioned earlier and then extended to commercial pharmaceutical formulations of the analytes of interest. The findings of the assay for determining the cited drugs in pharmaceutical tablets were statistically analysed with those of the published HPLC method, implying that no discernible difference exists between the suggested and published procedures. The analytical Eco scale, Agree metrics, and Green analytical procedure index was used to assess the method's greenness scores. The methods have been validated according to ICH criteria and confirmed to be within acceptable limits. [ABSTRACT FROM AUTHOR]

Introduction: Conventional methods of drug discovery have somehow proved to be ineffective in terms of lengthy design, limited efficacy amongst multiple other reasons. Considering that “time” is an important factor in the process of drug discovery, it becomes necessary to look for newer methods. Drug repurposing can be considered as a suitable option in such scenarios; to treat cancer or diseases with rapid pathogenesis. Amongst the various types of cancer, breast cancer and more precisely triple-negative breast cancer (TNBC) has become a prevalent form. Objectives: To overcome the challenges of conventional methods, several bioinformatic tools may be used, particularly those involved in molecular docking (CASTp, Discovery Studio, AutoDock Tools, etc.). Materials and Methods: Thiocolchicoside is a semisynthetic drug that was traditionally used as an anti-inflammatory and analgesic. In this article, we repurpose thiocolchicoside to act mainly on the NF-kB pathway. RANK and RANKL are frequently detected in the oncogenic process and together they participate in cancer development through TRAF6 activating the NF-kB pathway. Molecular docking of thiocolchicoside against TRAF6-RANK can exhibit the potency of this drug against breast cancer. Results: It was observed that cell viability was decreased when different drug concentrations were used against TNBS cell lines in vitro as compared with the control sample. The cell viability observed was 100% in the control sample, 95.93% in 15.625 µM drug concentration, 62.33% in 31.25 µM, 55.56% in 62.5 µM, 53.66% in 125 µM, 44.17% in 250 µM, and 39.84% in 500 µM. Conclusion: Repurposing a drug with the help of molecular docking is an effective method of drug development that reduces the time and cost factor due to its already known safety. Molecular docking of thiocolchicoside against TRAF6-RANK exhibits its inhibitory effect, and it can be effectively used as an anticancer drug.

Aims: The aim of this study was to evaluate the pharmacokinetic profiles and the relative bioavailability of dexketoprofen and thiocolchicoside of the test preparation (dexketoprofen/thiocolchicoside 25 mg/8 mg effervescent tablet) in comparison with the reference preparations (Keral 25 mg film coated tablet, containing dexketoprofen trometamol equivalent to 25 mg dexketoprofen (Menarini International Operations Luxembourg S.A.) (R1) and Muscoril 8 mg capsule, containing 8 mg thiocolchicoside (Sanofi Aventis İlaçları Ltd. Şti.) (R2) under fasting conditions. Methods: 25 healthy male subjects were enrolled in the study. Volunteers were hospitalised from the evening before drug administration (Day 0) until after the 24-hour blood sampling time on Day 2. Results: 24 subjects completed the study. Relative bioavailability (AUCT/AUCR1) of dexketoprofen from the test preparation was 100.99 %; (AUCT/AUCR2) of 3-O-glucuronide of thiocolchicoside (aglycone) from the test preparation was 100.47 %; (Cmax,T/Cmax,R1) of Dexketoprofen from the test preparation was 122.59 %; (Cmax,T/Cmax,R2) of 3-O-glucuronide of thiocolchicoside (aglycone) from the test preparation was 111.43 %. Conclusions: The relative bioavailability AUCT /AUCR of the test preparation compared with both reference preparations is comparable, as shown by the geometric mean ratios of 100.59 % (dexketoprofen) and of 98.20 % (3-O-glucuronide of thiocolchicoside (aglycone). [ABSTRACT FROM AUTHOR]

Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Our results showed that TCC induced tonic-clonic seizures that caused changes in electrocorticographic readings, characteristic of convulsive activity, with average amplitude greater than that induced by pentylenetetrazole. Treatment with anticonvulsants, especially diazepam, reduced the electrocorticographic outbreaks induced by TCC. The results suggested that TCC caused seizures with increased power in brain oscillations up to 40 Hz and that diazepam may partially reverse the effects.

Introduction Thiocolchicoside (THC) is a semi-synthetic derivative of colchicoside and a naturally occurring compound in the seeds of the Gloriosa Superba L.  plant. At present, it is used as a skeletal muscle relaxant. It is used to treat rheumatic arthritis, orthopaedic conditions, and trauma. Topically, it is used to relieve excruciating spasms in the muscles. It is also used to treat a wide range of conditions, which include surgical pain, cervicobrachial neuralgia, acute to chronic torticollis, Parkinson's disease, drug-induced Parkinsonism, spastic hemiplegia, tooth soreness, acute lower back pain, etc. THC is used in conjunction with non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and analgesics. By downregulating and inhibiting the synthesis of NF-κB-regulated gene products, it possesses anti-inflammatory properties. To prevent aneuploidy, the European Medical Agency has placed restrictions on the use of THC, stating that it should not be injected for five days or taken orally for longer than seven days. This is because its metabolism in the body may lead to the production of the metabolite M2. When used during pregnancy, the growing fetus is more negatively impacted. It has also been connected to infertility in men. Aim To study the skeletal muscle relaxant effects of THC in Wistar rats in comparison with standard drugs. Materials and methods The skeletal muscle relaxant activity level was measured using the rotarod apparatus. There were five groups of Wistar rats (n = 6). Group I received 0.9% normal saline (NS) as a control. Group II (test group) received THC 2 mg/kg intraperitoneally (ip). Group III (test group) received THC 4 mg/kg (ip). Group IV diazepam (DIZ) 3 mg/kg (ip) which is the standard treatment group. Group V received a combination of THC 2 mg/kg and DIZ 3 mg/kg. After treatment, retention time was noted at intervals of 30, 60, and 120 minutes. Results Group I (control), Group II (THC 2 mg/kg) and Group III (THC 4 mg/kg) did not demonstrate any skeletal muscle relaxant activity. Group IV (DIZ 3 mg/kg) and Group V (THC 2 mg/kg + DIZ 3 mg/kg) showed statistically significant skeletal muscle relaxant activity when compared to control. However, there was no statistically significant difference between the skeletal muscle relaxant activity of these two groups. This indicates that the addition of THC did not potentiate the skeletal muscle relaxant activity of DIZ. Conclusion THC didn't show skeletal muscle relaxant properties in both doses and did not potentiate the activity of DIZ., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: The Institutional Animal Ethics Committee of Krishna Vishwa Vidyapeeth (Deemed to Be University) Reg. No. 255/PO/REBi/S/2000/CPCSEA (IAEC Approval no. IAEC/KIMS/2021/1) provided approval. Guidelines of the Indian National Science Academy (INSA) and the Committee for Control and Supervision of Experiments on Animals (CCSEA) at the Central Animal House, KIMSDU, were followed during the study Issued protocol number 013/2020-21. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Devi et al.)

[Display omitted] • Expired vitamin B1 and phosphate were used as feedstock for carbon dots synthesis. • A fast green microwave-assisted synthesis of multidoped-carbon dots. • The multidoped-carbon dots have dual functions as nanosensor and photocatalyst. • The multidoped-carbon dots have been applied as a nanosensor for thiocolchicoside. • The multidoped-carbon dots were used as a photocatalyst for degradation of EBT dye. A fast and green synthesis of multi-doped carbon dots (multi-doped CDs) has been accomplished within 6 min of microwave treatment of a mixture of expired medicine, Vitamin B1, and phosphate salt as a feedstock. Characterization of the prepared quantum dots revealed multi-doping with nitrogen, sulfur, phosphorus, sodium, and chlorine. The prepared multi-doped CDs were applied for dual functions as an efficient photocatalyst and a sensitive fluorescence nanosensor that are not restricted by toxicity, cost, or stability. The efficient light absorption, electron transfer, and separation of photogenerated charge carriers within the multi-doped CDs enabled their use as an effective photocatalyst for remediation of organic dye-polluted water. Efficacious degradation of eriochrome black T dye (≈88 %) was accomplished within 80 min under visible light irradiation. Radical scavenging experiments demonstrated that the active species are hole, superoxide, and hydroxyl radicals. Furthermore, the multi-doped CDs were applied as a nanosensor for sensitive determination of the muscle relaxant drug thiocolchicoside (TCC) via fluorescence switch-off mechanism mediated by inner filter effect and dynamic quenching. The nanosensor was applied for the determination of TCC in its tablets with mean recovery % of 99.95 ± 1.55 and excellent selectivity. The present approach is a further step for circular economy applications hence it converts valueless chemical waste into valued products with useful applications. [ABSTRACT FROM AUTHOR]

This study aimed to formulate nano-cubosomes (NCs) co-loaded with capsaicin (CAP) and thiocolchicoside (TCS) to enhance their bioavailability and minimize associated potential side effects through transdermal delivery alongside their synergistic activity. Twenty seven (27) nano-cubosomal dispersions were prepared according to Box-Behnken factorial design and the effect of CAP, TCS, glyceryl mono oleate (GMO) and poloxamer 407 (P407) concentrations on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were assessed. The results revealed that the optimized formulation exhibited a mean droplet size of 503 ± 10.3 nm, PDI of 0.405 ± 0.02, zeta potential of −10.0 ± 1.70 mV and entrapment efficiency of 86.9 ± 3.56 %. The in vivo anti-inflammatory effect of optimized formulation was studied in rats by injecting carrageenan to induce edema. The results of in vivo study showed that transdermal application of nano-cubosomes co-loaded with CAP and TCS significantly (p value < 0.05) improved carrageenan induced inflammation compared with standard treatment. The analgesic activity of optimized formulation was evaluated in rats by using Eddy's hot plate method. The findings of analgesic activity illustrated that the analgesic effects exhibited by test formulation may be associated with increased licking period and inhibition of prostaglandins level. In conclusion, the transdermal application of NCs co-loaded with CAP and TCS may be a promising delivery system for enhancing their bioavailability as well as synergistic analgesic and anti-inflammatory activity in gout management. [ABSTRACT FROM AUTHOR]

Abstract Etodolac (ET) is a nonsteroidal anti-inflammatory drug (NSAID) that shows anti-inflammatory, analgesic, and antipyretic activities. Various NSAIDs have been demonstrated to enhance analgesia such as thiocolchicoside (TC) which is also an anti-inflammatory analgesic with muscle relaxant properties. A new quantitative method by using the data obtained from chemometrics calibration partial least squares (PLS), principal component regression (PCR), and inverse least squares (ILS) was developed for the simultaneous analysis of ET and TC without any separation process in combined pharmaceutical products. The calibration (25 samples) and validation (8 samples) concentration data matrices were prepared by using the mixtures containing ET (15–75 μg/mL) and TC (1–10 μg/mL) via factorial design method. The absorbance values were measured in the 240–440 nm. The recovery % of PLS, PCR, and CLS methods were found as ≤ 98.26%, 98.16%, and 98.17% for ET and 99.14%, 98.26%, and 98.15% for TC, respectively. These three chemometric techniques, which do not require neither separation nor derivatization steps, were confidentially applied for the determination of ET and TC in combined formulations. In conclusion, it is claimed that these new chemometrics-assisted spectrophotometric methods are inexpensive, rapid, and simple and can be trustfully carried out in quality control laboratories as an alternative to existing methods.

Context: Musculoskeletal pain is usually associated with inflammation and muscular spasm which further contributes to the elevation of pain. Traditionally, nonsteroidal anti-inflammatory drugs (NSAIDs) are employed in the treatment of pain. Literature review reveals that the benefits were more significant in terms of overall symptom reduction, when the patients suffering from musculoskeletal pain were administered the combination of a NSAID & a muscle relaxant. Aims: The present study was undertaken with the aim to assess the efficacy and safety of fixed-dose sustained-release combination of aceclofenac and thiocolchicoside in patients with acute inflammatory conditions associated with muscle spasm. Settings and Design: A multicenter, prospective, open-label, noncomparative clinical study was carried out in 442 patients with clinical diagnosis of inflammation associated with spasm. Subjects and Methods: fixed-dose combination of aceclofenac (200 mg) and thiocolchicoside (8 mg)-sustained-release capsules was orally administered once daily for 2 weeks. Results: The treatment led to significant pain reduction from the baseline noted with visual analog score at the 1st week itself. After 2 weeks of treatment, the mean pain score declined by 90%, joint tenderness improved in 90% of the patients, and the mean joint mobility scores were near normal in most of the patients. Furthermore, at the end of the treatment, nearly all of the patients were symptom free. No serious adverse events were reported. Conclusions: The current study confirms that fixed-dose combination of aceclofenac and thiocolchicoside in sustained-release form is effective and well tolerated in the treatment of patients with acute musculoskeletal inflammatory conditions.

In this study, a differential pulse voltammetry method was designed for the simultaneous determination of etodolac and thiocolchicoside in a tablet dosage form. This method is a sensitive, costless and reproducible one initially designed for the simultaneous determination of etodolac and thiocolchicoside using bare/unmodified glassy carbon electrode in the presence of sodium dodecyl sulfate. At optimized conditions, the method showed linear responses with etodolac and thiocolchicoside concentration in the range of 1 μM to 80 μM. The limits of detection and quantification were calculated as 0.11 μM and 0.38 μM for etodolac and 0.20 μM and 0.67 μM for thiocolchicoside, respectively. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study of this study was to discover the best poloxamer as a solid dispersion carrier for thiocolchicoside (TCS). Materials and Methods: The compatibility of TCS with excipients was studied by differential scanning colorimetry and fourier transform infrared spectroscopy. Different formulations of solid dispersions (SDs) were made with poloxamer carriers, i.e. poloxamer-108, poloxamer-188, poloxamer-237, poloxamer-338, and poloxamer-407 were made by taking TCS:poloxamer in ratios of 1:1, 1:2, 1:4, and 1:6. The SDs were made by a novel microwave fusion method and compressed using an 8-station tablet compression machine. The fabricated SD tablets were characterized by physicochemical constraints and drug release rates. The release of TCS from the prepared SDs was later analyzed by kinetic models. Results: TCS was observed to be compatible with the poloxamer carriers. The SD formulations showed satisfactory physicochemical constraints and TCS release following first-order release. Conclusion: Among the poloxamer carriers used, poloxamer-188 was the best for increasing the solubility and release rate of TCS from the SDs. [ABSTRACT FROM AUTHOR]

This study describes the antiproliferative activity of thiocolchicoside and colchicine compounds in a dose-dependent manner against breast cancer cell line (MCF-7). MTT assay results show that IC50 (inhibitory concentration 50 %) values towards MCF-7 breast cancer cell line were 79.02 and 74.23 nmol for thiocolchicoside and colchicines compounds, respectively. Further, in vitro interaction between thiocolchicoside and colchicine compound ligands binding with the p53 tumor suppressor protein gene and its expression was also confirmed by western blot analysis. Results clearly show that the expression of p53 protein was more abundant in treated MCF-7 cancer cell line and up-regulated expression of the p53 gene was positively correlated with thiocolchicoside and cochicine concentrations used. The thiocolchicoside compound was found to be more effective against p53 protein accumulation levels when compared with colchicine and adriamycin. Molecular docking analysis was performed to reveal the interactions of receptor binding sites (molecular targets) with ligands. These compounds show efficient inhibitory action on the target p53 tumor suppressor protein expression which confirms their increased anti-proliferative activity against cancer cell growth. The present results could be used for the improvement of a novel formulation with enhanced inhibition of MCF-7 cancer cell growth. The docking scores were found to be high in thiocolchicoside compound against cellular tumor antigen p53 (-5.9 kcal/mol) with the strong interaction followed by colchicine (-5.3 kcal/mol) and the hydrogen bond counts, confirming the capability of these compounds for binding with receptor active site. Therefore, thiocolchicoside and colchicine compounds with effective p53 inhibitory activity strongly suggest that these compounds could be used as strong anticancer agents to treat MCF-7 breast cancer cell growth arrest effectively. [ABSTRACT FROM AUTHOR]

A rapid, simple, sensitive, precise and specific square wave voltammetric method was developed for the simultaneous determination of Thiocolchicoside (TC) and Diclofenac diethyl ammonium (DDA) in topical gel formulation. The combination of TC and DDA have synergetic action on the treatment of rheumatoid arthritis and other related conditions. The optimum conditions were obtained in Britton–Robinson buffer pH 3.00 for electroreduction at hanging mercury drop electrode. Well-defined peaks were observed for TC at –0.85 V, and for DDA at –1.18 V vs. Ag/AgCl/4.6 M KCl. Under optimum conditions, the linear response ranges for determination of TC and DDA were 1.07–24.2 µM and 5.64–45.8 µM, with detection limits of 0.54 and 3.25 µM, respectively. The electrochemical behaviors of the substances such as current type and reversibility of the electrode reactions were investigated by using cyclic voltammetry. The reduction mechanisms were also proposed. The method was validated with respect to accuracy, precision, sensitivity and specificity according to the International Conference on Harmonization guidelines. The developed method was applied for the simultaneous determination of TC and DDA in topical gel formulation including binary mixtures. The excipients present in the formulation did not interfere with the assay. The method is suitable for application in quality-control laboratories, because it is simple and rapid with high accuracy and precision. [ABSTRACT FROM AUTHOR]

Background: The goal of this work was to synthesize and fabricate matrix type transdermal patches based on a combination of polymers (Eudragit L100, HPMC and PVP K30), plasticizer and crosslinking agents (propylene glycol and triethyl citrate) and adhesives (Dura Tak 87-6908) to increase Thiocolchicoside (THC) absorption via topical route. This method allows avoidance of first-pass metabolism along with a consistent and extended duration of therapeutic activity., Methods: Fabrication and casting of polymeric solutions containing THC was done either in petri plates or through lab coater to get transdermal patches. Finally, the formulated patches were studied for their physicochemical and biological evaluation using scanning electron microscopy, FTIR, DSC, XRD and ex-vivo permeation studies using pig ear skin., Results: FTIR studies confirm that the THC characteristics peaks (carbonyl (Amide I) at 1525.5 cm -1 , C=O stretching (tropane ring) at 1664.4 cm -1 , Amide II band (N-H stretching) at 3325.9 cm -1 , thioether band at 2360.7 cm -1 , and OH group stretching band at 3400.2 cm -1 ) are still present in the polymer mixture even after formulation as a transdermal patch, indicating compatibility among all excipients. While on the other hand, DSC studies confirm endothermic peaks for all the polymers along with THC with the highest enthalpy of 65.979 J/g, which is an indicator of sharp endothermic peak at 198°C, leading to the melting of THC. The percentage drug content and percentage moisture uptake of all the formulation was found in the range of 96 ± 2.04 to 98.56 ± 1.34% and 4.13 ± 1.16 to 8.23 ± 0.90%, respectively. Drug release and release kinetics studies confirm that it is dependent on the composition of individual formulation., Conclusion: All these findings support the possibility of using suitable polymeric composition, as well as proper formulation and manufacturing circumstances, to create a one-of-a-kind technology platform for transdermal drug administration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, an Inverse Phase‐High Performance Liquid Chromatography method was developed for the determination of the quantities of Etodolac and Thiocolchicoside active ingredients contained in the same tablet form (Etotio tablet). For this purpose; Etodolac and Thiocolchicoside in the pharmaceutical combination were determined simultaneously using Inverse Phase‐High Performance Liquid Chromatography method. This developed high‐performance liquid chromatography method was also used for the simultaneous in vitro quantity determination of Etodolac and Thiocolchicoside in human plasma. Plasma samples were analyzed with the Inverse Phase‐High Performance Liquid Chromatography method without any need for extraction process and very high recoveries were obtained with this chromatographic method. Method validity was tested by applying all the validation parameters for the data obtained from both studies (in solvent and plasma media). Results obtained in plasma media and solvent media were compared statistically with Anova test and it was found that there is no significant difference (at 95% possibility level) between the two methods from average and standard deviation aspects. [ABSTRACT FROM AUTHOR]

Highlights • Three novel and four known degradants of thiocolchicoside were isolated and characterized by NMR and HRMS techniques. • The stereochemistry in DP-4 diastereomers was confirmed by ROESY1D. • Sulphoxide product which was found to be mixture of diastereomers were separated by SFC. • Three novel degradants were obtained in base mediated hydrolysis have six membered ring in place of cycloheptatrienone of thiocolchicoside. Abstract Thiocolchicoside is a natural product analogue often used for its spasmolytic action. To know more about its stability under various stress conditions, the drug was stirred in acid, base and peroxide solutions. In acid hydrolysis, two products were obtained and in both, the glucose got cleaved. In one of them the acetyl group also got cleaved. A set of two diastereomers were formed during the peroxide mediated hydrolysis. The base mediated hydrolysis resulted in formation of three novel degradants. They have six membered rings in their structures instead of a seven membered cycloheptatrienone. Structures of known and novel degradation products have been elucidated by extensive analysis of HRMS, 1D and 2D NMR spectroscopic techniques. [ABSTRACT FROM AUTHOR]

A simple, rapid, and robust stability indicating RP-HPLC method has been developed and validated to measure thiocolchicoside (TH) and diclofenac potassium (DP) at single wavelength (258 nm) in order to assess assay and in vitro drug release profile of drug from tablet formulation. A gradient elution of samples performed on Zorbax SB CN 250 mm × 4.6 mm, 5 μm column with buffered mobile phase consisting solvent A (5 mM sodium dihydrogen phosphate, pH 2.5) and solvent B (methanol) delivered at flow rate 1.0 mL/min. For dissolution study, the sink condition has been established from quantitative solubility of TH and DP API in different dissolution medium recommended by USP for immediate release formulation and the optimized dissolution condition was: pH 6.8 deaerated potassium dihydrogen phosphate buffers, paddle rotation speed 50 rpm and vessel volume 900 mL. Discriminating release of TH and DP achieved more than 96% of labeled amount over 45 min and drug dissolution was concluded after 60 min. The HPLC method and dissolution test condition were validated to meet requirement for regulatory filling and this validation inferred from specificity, precision, accuracy, linearity and robustness. In addition filter suitability, standard and sample solution stability was demonstrated.All results were acceptable and this confirmed that the method is suitable for its intended use in routine quality control and assay of drugs.

It is of interest to develop potent and safer anti-inflammatory drugs from plants, as medicinal plants and herbs attained great attention in the medical world due to their multifunctional activities. This article studied the anti-inflammatory effects of lauric acid (LA), thiocolchicoside (TC) and thiocolchicoside-lauric acid (TC-LA) formulation. The anti-inflammatory effects of these compounds were determined by following the methods of inhibition of protein denaturation and proteinase inhibition activity. This was assessed at different concentrations to determine the 50% inhibition concentration (IC50) of the compounds. The result indicated that the activity of LA, TC, TC-LA formulation, and reference drug increased with the increase in the concentration from 10-50 µg/ml, thus proving the activity of LA, TC, and TC-LA formulation against inflammation was in a dose-dependent manner. The percentage of inhibition of protein denaturation was 59.56%, 66.94%, 86.62%, and 60.34% for LA, TC, the combination of TC-LA and standard drug, and the IC50 values were found to be 44.78 µg/mL, 37.65 µg/mL, 27.15 µg/mL and 43.42 µg/mL, respectively. The percentage of proteinase inhibition activity of LA, TC, and a combination of TC-LA and the standard drug was 66.65%, 77.49%, 94.07%, and 69.83%, and IC50 of LA, TC, a combination of TC-LA and standard drug were35.5 µg/mL, 32.12 µg/mL, 24.35 µg/mL and 37.80 µg/mL, respectively. We found out that lauric acid, thiocolchicoside, and thiocolchicoside-lauric acid formulation exhibited significant anti-inflammatory activity., (© 2023 Biomedical Informatics.)

Background Low back pain (LBP) is a global health concern. Management of LBP aims at pain relief facilitating improvement of functional ability. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first line of therapy. However, the selection of NSAIDs is challenging given the range of underlying etiologies and severity. The current study aimed to compare the efficacy and safety of two available fixed-dose combinations (FDCs), namely, a dual FDC (DFC) of etoricoxib (60 mg) and thiocolchicoside (4 mg) versus a triple FDC (TFC) of chlorzoxazone (500 mg), diclofenac (50 mg), and paracetamol (325 mg). Methodology A total of 200 eligible adult subjects aged 18-70 years with a history of LBP and muscle spasm for ≤14 days and Wong-Baker Faces Pain score >4 were enrolled after obtaining written informed consent and randomized in a 1:1 allocation ratio to be treated with either DFC or TFC for 28 days. Efficacy was assessed based on the change in score from baseline (before treatment) to day 28 on the Wong-Baker Faces Pain Scale and the Oswestry Disability Index (ODI) questionnaire, as well as the proportion of subjects who improved upon treatment. Safety was assessed based on adverse events and clinical laboratory test results. Results A significant decrease in pain intensity (p < 0.001) and significant improvement in functional ability (p < 0.001) was observed after treatment with either DFC or TFC. The decrease in Wong-Baker Faces Pain score and ODI, from baseline, was comparable between the treatment groups. However, more subjects with very severe pain at baseline showed ≥30% improvement upon treatment with DFC than with TFC (~25% versus ~12%; p = 0.172). Also, significantly more crippled subjects with very severe functional disability showed improvement in the DFC group compared to the TFC group (~26% versus ~4%; p = 0.008). No adverse events or clinically relevant laboratory test results were evident. Conclusions Both DFC and TFC were comparable in efficacy and safety for the management of recent-onset LBP. However, significantly more subjects with very severe pain or functional disability showed improvement after 28 days when treated with DFC compared to TFC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Karmakar et al.)

A robust and eco-friendly stability-indicating high-performance thin-layer chromatography (HPTLC) method was developed for the stability study of thiocolchicoside using analytical quality- by-design approach. Full factorial design was used for screening potential variables affecting method development. Box-Behnken design was used subsequently for investigation of the main, interactive, and quadratic effects of these variables on response. Four potential variables were selected on the basis of scientific knowledge for the development of a method for the stability study of thiocolchicoside. The selected potential factors, namely, volume of water (mL), saturation time (min), migration distance (mm), and volume of mobile phase (mL) were screened by 24 full factorial designs by selecting resolution as a critical method attribute. Pareto chart analysis showed that 3 variables, namely, volume of water (mL), saturation time (mm), and migration distance (mm), out of 4 potential variables were significantly affecting the response variable (resolution). Optimization with response surface methodology further clarified the relationship between critical variables and resolution using Box-Behnken design. The experimental design model was found to be quadratic, and the design space was developed on the basis of suggested model for optimization of critical method variables for maximum desirable resolution and for the development of a control strategy of the HPTLC method for the stability study of thiocolchicoside. The developed method was validated for linearity, range, specificity, precision, accuracy, limit of detection and limit of quantification as per the International Conference on Harmonization guidelines (ICH) Q2 (R1). The developed method was applied for the estimation of thiocolchicoside in its pharmaceutical dosage forms. The degradation products formed in acidic and alkaline media were isolated and characterized by their infrared (IR), nuclear magnetic resonance (NMR), and mass spectral data. [ABSTRACT FROM AUTHOR]

Objective The 2014 report by European Medicines Agency (EMA) restricted the use of thiocolchicoside for all reproductive-age women. In this study, we aim to expand the systematically-collected human data and discuss it within the frame provided by this report. Methods We identified and evaluated the outcomes of 48 prospectively recorded pregnancies referred to Terafar (Teratology Information Service, Izmir, Turkey). Results Of 42 pregnancies with first-trimester exposure and known outcomes, 31 resulted in live births, four in miscarriage and seven ended with elective terminations. There were 26 normal outcomes, two major and three minor congenital malformations among the live births. Conclusions Despite a number of limitations, our results and previous case series collectively strengthen the view that thiocolchicoside is unlikely to be a major teratogen. EMA’s 2014 report should be revised to reflect this finding, while current restrictions on use should continue until more detailed safety information is available. [ABSTRACT FROM AUTHOR]