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Background Lower third molar surgery is very commonly performed for minor oral surgery by an oral and maxillofacial surgeon. One of the main chief complaints that patients report back to the clinic after getting their lower third molar impaction surgery is immediate postoperative pain. In our study, we have compared the efficacy of ketorolac tromethamine diluted saline solution over plain saline solution used as an irrigant in reducing postoperative swelling and pain. Aim The aim of the current study is to analyse the efficiency of ketorolac tromethamine diluted saline solution over normal saline without any drug dilution in reducing postoperative sequelae like pain and swelling after surgical removal of the lower third molar. Materials and methods This study was carried out at the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, from April 2023 to July 2023. The study included 50 individuals who wanted to prophylactically get the lower third molar removed surgically. These participants were divided into two groups. One group received ketorolac diluted saline irrigant while the other group received plain saline (0.9% NaCl) as irrigant. Postoperatively, pain and swelling were evaluated in both groups. Both pain and swelling were measured preoperatively, postoperatively after 48 hours, and postoperatively after seven days. The swelling was measured using a 4-point measuring scale, and pain measurement was done using a 10-point visual analogue scale. Statistical analysis was done using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). For the comparison of continuous variables between the two groups, an unpaired t-test was used. The normality of the results obtained was checked using the Shapiro-Wilk test. The results were considered statistically significant if the P-value was less than 0.05. Results Based on the results obtained it was found that participants who were included in the ketorolac saline group had comparatively lower postoperative pain scores than participants in the plain saline group and this was statistically significant (P=0.001). Postoperative swelling was also comparatively lower in the ketorolac tromethamine saline group but the results were not statistically significant at the end of day 7 (P=0.09). Conclusion Upon observing the cumulative results obtained, we conclude that ketorolac saline (10mg/100mL) was more efficacious in terms of pain reduction than the regular saline solution in impacted lower third molar surgery.

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INTRODUCTION: There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment. METHODS: Participants (≥ 65 years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60-89 mL/min for mild and 30-59 mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25 mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75 mg/h continuous intravenous (IV) infusion over 24 h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15 mg every 6 h. There were four treatment periods of 24 h for each subject with a minimum 7-day washout between them. This was a crossover study so subjects served as their own controls. Blood drawn from the subjects was used to plot concentration-time profiles against target profiles. Adverse events were monitored. RESULTS: Thirty-nine subjects enrolled. Concentration-time profiles showed low intersubject variability. Model-predicted curves for those with renal impairment closely matched observed plasma concentrations. Continuous infusion maintained higher mean plasma concentrations than the bolus regimen. No serious or unexpected adverse events were observed. No deaths occurred. CONCLUSIONS: NTM-001 was considered safe and well tolerated in this population of participants ≥ 65 years, including in those with mild or moderate renal impairment. There were fewer adverse events in the continuous infusion group. The predictable pharmacologic properties and blood concentration levels suggest that continuous IV infusion of ketorolac can be used as an effective postoperative pain reliever in older subjects.

Controlling postoperative pain can lead to faster recovery. Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID), like ibuprofen and naproxen, that can be as effective as morphine without the same risks. In hospitals, ketorolac is usually administered intravenously (IV) either continuously or as a bolus injection. A bolus of ketorolac may result in adverse gastrointestinal side effects. In this study, a new formulation of ketorolac tromethamine, NTM-001, was administered IV as a continuous 24 h infusion compared to IV boluses of ketorolac tromethamine every 6 h in volunteers. Volunteers were older (≥ 65 years) and had no, mild, or moderate kidney dysfunction. One randomized group received a starting IV dose of 6.26 mg followed by a continuous IV infusion of 1.75 mg/h of over 24 h. The other group received single NTM-001 IV bolus injections of ketorolac tromethamine 15 mg every 6 h over 24 h (4 doses, 60 mg) over the 24 h. After completing the first study, subjects waited at least a week and then switched groups, giving the study a crossover design so it could be observed how each subject responded to both regimens. Blood drawn from the subjects was tested for standard pharmacokinetic (PK) parameters. The data show that blood concentrations of NTM-001 can be reliably predicted. Side effects were mild and the continuous infusion reduced side effects. No unexpected adverse events occurred. These data show that NTM-001 can be used safely in older individuals, including those with mild or moderate kidney impairment.

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Aim: The fixed-dose combination of moxifloxacin (MOXI) and ketorolac tromethamine (KTR) is widely used for the treatment of bacterial keratitis. Thus, a new LC-MS/MS method was developed to determine MOXI and KTR in lacrimal fluid. Methods: Bioanalysis was performed using a Shimadzu 8050 LC-MS/MS in electrospray ionization-positive mode and the method was validated per US FDA guidelines. Isocratic separation was performed with a Waters Symmetry C18 column using methanol and 0.1% formic acid containing deionized water (85:15, v/v). Results & conclusion: An easy, quick and selective method was established and applied to assess the ocular pharmacokinetic profile of a commercially available formulation containing MOXI and KTR. Based on the pharmacokinetic data, this work describes pharmacokinetics-based dosage regimen calculations and their clinical significance.

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Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 µg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.

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INTRODUCTION: There is an urgent unmet medical need for a safe, effective, nonopioid analgesic agent for postoperative pain control. METHODS: This first-in-man study was designed to explore a data-informed, model-based candidate dosage regimen and safety of a novel formulation of ketorolac tromethamine (NTM-001) delivered as a 12.5-mg intravenous (IV) bolus followed immediately by 3.5 mg/h continuous infusion over 24 h compared versus IV bolus dosing of 30 mg generic ketorolac every 6 h. The study evaluated pharmacokinetic parameters and safety profiles based on a targeted product profile. A graphical overlay method and model-based comparisons were used to assess the concentration-time curve. RESULTS: Healthy adults (n = 28, 50% men) received NTM-001 and bolus dosing in an open-label crossover design. Observed plasma concentrations were tightly aligned with predicted values with no outliers. Graphical overlay comparisons showed low between-subject variability and agreed with forecasted concentration-time targets. The pharmacokinetic (PK) base models fit with preliminary PK data from both the NTM-001 and bolus groups with model fit median profiles within 95% prediction limits and no updating of the models. Consistent with serum concentration-time profiles, pain relief scores fell within predicted limits, with initial pain relief scores of NTM-001 slightly above the target profile, likely because the initial serum ketorolac concentrations were somewhat higher than predicted. The 24-h pain relief predicted for NTM-001 based on the area under the median ketorolac pain relief versus time curve was about 6% below that of the pain relief target. Both treatments were well tolerated and no subject withdrew because of adverse events. CONCLUSIONS: The PK parameters for NTM-001 and comparator bolus were similar to the modeling targets with no updating of the base model. There were no outliers and little intersubject variability. NTM-001 delivered as a bolus of 12.5 mg IV followed immediately by continuous infusion of 3.5 mg/h using a standard hospital infusion pump may offer an alternative to opioids for acute postoperative pain control.

Opioids are effective analgesics but the risk for opioid use disorder (OUD) and opioid-associated side effects limit their use even for postoperative pain. Ketorolac is an established nonopioid pain reliever that may be as efficacious as morphine in this setting. This study evaluated a new ketorolac product (NTM-001) compared to generic ketorolac. Both were delivered using a standard hospital intravenous (IV) drug pump. The new ketorolac product was administered first with a loading dose of 12.5 mg followed immediately by a continuous IV infusion of 3.5 mg/h. This was compared to IV generic ketorolac administered as a bolus dose of 30 mg every 6 h. The study enrolled 28 healthy adult volunteers. As a crossover study, subjects underwent both treatments: once with the continuous infusion (NTM-001) and once with the IV injection every 6 h (bolus group) with a "washout" period in between. Blood was collected from the volunteers at several time-determined points during the 48-h study to chart ketorolac concentrations in the blood, which can be correlated to predicted levels of pain control. In this study, blood concentrations of ketorolac were reliably predictable and side effects were generally mild with no unexpected adverse events. The continuous infusion group achieved analgesic benefit at a lower total dose than did the every-6-h group over 24 h.

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Objective To investigate the effectiveness and safety of acetaminophen combined with ketorolac tromethamine in pain management early after laparoscopic cholecystectomy(LC).Methods Ninety patients with LC under general anesthesia,42 males and 48 females,aged 18-78 years,BMI 18-28 kg/m2,ASA physical statusⅠorⅡ,were selected and randomly divided into two groups by random num-ber table method:the acetaminophen combined with ketorolac tromethamine group(group AK)and the nal-buphine group(group NA),45 patients in each group.Group AK received 500 mg(diluted to 50 ml)of acetaminophen injection and 30 mg of ketorolac tromethamine(diluted to 10 ml)injection pumped 15 mi-nutes before induction of anesthesia,and group NA received 50 ml of NS injection and 0.2 mg/kg of nalbu-phine(diluted to 10 ml)injection pumped at the same time.Postoperative pain was recorded 0.5,3,6,12,and 24 hours after surgery using VAS pain scores(the non-inferiority boundary Δ = 1.0 score).The sleep quality score on the night of surgery,the number of remedial analgesia cases within 24 hours after sur-gery,the Ramsay sedation score 0.5,3,and 6 hours after surgery,the occurrence of adverse reactions such as nausea and vomiting within 24 hours after surgery,and the overall satisfaction of patients were recorded.Results Compared with group NA,the VAS pain scores 0.5 hour after surgery was reduced in group AK(P＜0.05).The sleep quality score and overall satisfaction in group AK were significantly higher than those in group NA(P＜0.05).There were no significant differences in the rate of remedial analgesia,the score of Ramsay sedation at different time points and the incidence of nausea and vomiting within 24 hours after surgery between the two groups.Conclusion Acetaminophen combined with ketorolac tromethamine is not less effective than nalbuphine in relieving early postoperative pain after laparoscopic cholecystectomy without increasing the incidence of nausea and vomiting.Patients receiving acetaminophen combined with ketorolac tromethamine have higher sleep quality scores on the night of surgery and overall satisfaction.

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BACKGROUND: To determine the effect of ketorolac tromethamine 0.5% in preventing post-phacoemulsification macular thickening. This randomized clinical trial. patients randomized 1:1 to receive either topical ketorolac three times a day or a placebo. METHODS: A total of 101 eyes of 101 diabetic patients who were scheduled for phacoemulsification and had normal macular contour and thickness enrolled consecutively. The topical ketorolac and placebo were prescribed on the day before surgery and continued up to 4 weeks after surgery. Patients with proliferative diabetic retinopathy, a history of intravitreal injection in less than three months, a history of macular photocoagulation in less than 6 months, and any other concomitant ocular pathologies were excluded. Central macular thickness (CMT) and best corrected visual acuity (BCVA) was recorded in the follow-ups of 6, 12, and 24 weeks after the surgery and compared with the controls. RESULTS: 49 eyes in the case group and 52 eyes in the control group were analyzed. Mean BCVA was significantly improved in both groups at all follow-ups (P < 0.001 for all). There was no statistically significant difference regarding the BCVA in different time points except week 12 (P = 0.028) among the study group. In the case and control groups, CMT was increased at all follow-ups (P < 0.05). There was no statistically significant difference when comparing the two groups regarding the mean of CMT at any time point postoperatively (P > 0.05 for all). CONCLUSION: Based on our findings, topical ketorolac tromethamine 0.5% is not effective in the prevention of post-phacoemulsification macular thickening in diabetic patients. TRAIL REGISTRATION: The study protocol was registered into www. CLINICALTRIAL: gov with the RCT registration number NCT03551808. (2018/06/11 ) CLINICAL TRIAL REGISTRATION NUMBER: NCT03551808.

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The high prevalence of opioid addiction and the shortcomings of systemic opioids has increased the pace of the search for alternative methods of pain management. The local delivery of pain medications has started to be used as a tool for pain management and to decrease the use of systemic opioids for these patients. Here, we explored an in-situ polymerizable hydrogel system for the local delivery of analgesics and nonsteroid anti-inflammatory drugs (NSAID) for orthopaedic applications. We synthesized a series of methacrylated oligomeric polyethylene glycol-co-lactic acid polymer using microwave radiation for the delivery of bupivacaine hydrochloride as an analgesic and ketorolac tromethamine as an NSAID. We determined drug elution and gel degradation profiles in vitro. Biocompatibility was assessed against osteoblasts in vitro and by histological analysis after subcutaneous implantation for 4 weeks in vivo. Intra-articular and systemic concentrations and pharmacokinetic parameters were estimated using a two-compartment pharmacodynamic model based on in-vitro elution profiles. This type of in-situ applicable hydrogels is promising for extending the local efficacy of pain medication and further reducing the need for opioids.

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Introduction Headaches are a common presentation to the emergency department, representing approximately 3% of visits. The standard treatment of headaches has consisted of either monotherapy with an antidopaminergic agent or combination therapy with an antidopaminergic agent, a non-steroidal anti-inflammatory drug (NSAID), and diphenhydramine. Although droperidol is an antidopaminergic medication, it previously was not widely used in the treatment of headaches due to safety concerns. Given its pharmacokinetics, droperidol may provide faster relief in migrainous headaches compared to more commonly used antidopaminergic agents. Methods We conducted a single-center retrospective chart review to examine the impact of droperidol compared to other standard migraine therapies on pain scores. The study consisted of three treatment arms: droperidol monotherapy, a droperidol bundle (droperidol and ketorolac), and a prochlorperazine bundle (prochlorperazine and ketorolac). Patients who received medications in treatment arms and who had an encounter diagnosis including either "headache" or "migraine" were included. Patients were excluded if under 18 years of age, imprisoned, pregnant, or received potentially migraine-altering medications prior to the first documented pain score. The primary outcome was a mean reduction in pain scores. Secondary outcomes included length of emergency department stay, rates of inpatient admission, need for rescue therapies, and adverse events. Results A total of 361 droperidol orders were reviewed, of which 79 met the inclusion criteria. Of those included, 30 orders were within the droperidol monotherapy arm, 19 were within the droperidol bundle arm, and 30 were within the prochlorperazine bundle arm. There were no significant differences in reduction of pain scores, emergency department length of stay, rates of inpatient admission, rates of rescue therapy, or adverse events between the three treatment arms. Conclusion In this study, we found no statistical difference in migraine treatment efficacy between droperidol monotherapy and droperidol and prochlorperazine-based bundle therapies. Further studies are needed with larger sample sizes and predefined timing between pain score charting and medication administration.

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of inflammatory pain, such as in osteoarthritis. Ketorolac tromethamine is considered to be an NSAID with strong anti-inflammatory and analgesic potency, however, traditional applications, such as oral administration and injections, often induce high systemic exposure, leading to adverse events such as gastric ulceration and bleeding. To address this key limitation, herein we designed and fabricated a topical delivery system for ketorolac tromethamine via cataplasm, which is based on a three-dimensional mesh structure formed by the cross-linking of dihydroxyaluminum aminoacetate (DAAA) and sodium polyacrylate. The viscoelasticity of the cataplasm was characterized by rheological methods and exhibited a "gel-like" elastic property. The release behavior showed a Higuchi model characteristic with a dose dependence. To enhance the skin permeation, permeation enhancers were added and screened utilizing ex vivo pig skin, in which 1,2-propanediol was found to have the optimal permeation-promoting effect. The cataplasm was further applied to a rat carrageenan-induced inflammatory pain model, which showed comparable anti-inflammatory and analgesic effects with oral administration. Finally, the biosafety of the cataplasm was tested in healthy human volunteers, and reduced side effects were achieved as compared to the tablet formulation, which can be ascribed to less systemic drug exposure and lower blood drug concentrations. Therefore, the constructed cataplasm can reduce the risk of adverse events while maintaining efficacy, thus serving as a better alternative for the treatment of inflammatory pain, including osteoarthritis.

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PURPOSE: To observe the effect of ketorolac tromethamine combined with remifentanil in sedation and analgesia during general anesthesia emergence and reducing general anesthesia complications. DESIGN: This is an experimental design. METHODS: A total of 90 patients who underwent partial or total thyroidectomy in our hospital were selected and randomly divided into three groups with 30 cases in each group. Routine general anesthesia combined with endotracheal intubation was given for general anesthesia, and different treatments were administered when the skin was sutured. Group K: intravenous injection of ketorolac tromethamine 0.9 mg/kg, intravenous injection of normal saline 10 mL/h by micropump until awakening and extubation; R group: intravenous injection of normal saline 2 mL, micropump intravenous injection of remifentanil 0.1 mcg/kg/min until awakening and extubation; KR group: intravenous injection of ketorolac tromethamine 0.5 mg/kg, micropump intravenous injection remifentanil 0.05 mcg/kg/min until awakening and extubation. After the operation, all patients entered the postanesthesia care unit (PACU) for recovery, extubation, scoring. The incidence and condition of various complications were counted. FINDINGS: There was no significant difference in the general information or operation duration of the patients (P > .05). The types of general anesthesia induction drugs in each group were the same, and there was no significant difference in drug measurement (P > .05). The visual analogue scales of KR group were: 2.2 ± 0.6(T0) and 2.4 ± 0.9(T1), the Self-Rating Anxiety Scale scores of the KR groups were: 4.1 ± 0.6(T0), 3.7 ± 0.4(T1). Compared with the KR group, the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were increased (P < .05); the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were not significantly different (P > .05); at T2, there was no significant difference in visual analogue scale and Self-Rating Anxiety Scale scores among the three groups (P > .05). There was no significant difference in extubation time or PACU transfer time among the three groups (P > .05). The incidence of adverse reactions in KR group were: 3.3% (nausea), 3.3% (vomit), 0 (coughing and drowsiness). Compared with the KR group, the incidence of adverse reactions was higher in the K and R groups. CONCLUSIONS: Ketorolac tromethamine combined with remifentanil can effectively relieve pain and sedation during general anesthesia recovery and reduce the incidence of complications related to general anesthesia recovery. At the same time, the application of ketorolac tromethamine can reduce the dosage of remifentanil and inhibit the occurrence of adverse reactions when used alone.

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Pharmaceuticals, which have been praised for protecting countless lives, have become a new category of environmental pollutants in recent decades as most of these pharmaceutical compounds are discovered in water bodies in concentrations ranging from ng/L to mg/L. Recently, metal-free g-C3N4 (GCN)-based composites have received considerable attention for the degradation of pharmaceutical compounds. In this study, GCN/BiOCl composite was prepared using a simple ultrasonication-assisted stirring method and characterized using various analytical and spectroscopic techniques including XRD, FTIR, PL, Elemental mapping, UV-DRS, FESEM, HRTEM, and TGA. The as-prepared composite was utilized to degrade levofloxacin (LVX) under solar light irradiation and showed excellent stability for the degradation of LVX. Furthermore, the universality of the GCN/BiOCl composite was investigated by degrading diverse pharmaceuticals such as ofloxacin (OFX), norfloxacin (NOX), ciprofloxacin (COX), and ketorolac tromethamine (KTC) in an aqueous phase. Therefore, this work provides an effective method to degrade pharmaceutical contaminants simultaneously in water using GCN/BiOCl composite.

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BACKGROUND: Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug from the heteroaryl acetic acid derivatives family. The most widely used new nanotechnological approaches for topical drug delivery are polymeric nanoparticles (NPs). OBJECTIVE: Successful results have been obtained with low doses in many treatments, such as cancer, antimicrobial, pain, made with nanoparticle formulations of drug active ingredients. METHODS: NPs were prepared using Nano Spray-Dryer. The cytotoxicity of the optimum formulation in BJ (ATCC® CRL-2522™) human fibroblast cells was determined by the WST- 1 method and the gene activity was elucidated by mRNA isolation and real-time polymerase chain reaction (RT-PCR). The in vivo HET- CAM assay was performed for anti-inflammatory activity. RESULTS: NPs presented PDI values lower than 0.5, and therefore particle size distribution was decided to be monodisperse. Positive zeta potential values of NPs highlighted the presence of the cationic ammonium group of Eudragit® RS 100. The release rates observed from KT-NP coded formulations after 24 hours were 78.4% ± 2.9, demonstrating extended release from all formulations, relative to pure KT. The lowest concentration of KT-NP increased fibroblast cell proliferation higher than the highest concentration of KT. The 5-fold increased effect of KT-NP formulation on collagen gene expression compared to KT is also related to the enhanced anti-inflammatory effect in line with the in vivo HET-CAM assay results. CONCLUSION: With the obtained cell viability, gene expression, and HET-CAM results, it has the hope of a successful nano-topical formulation, especially in both wound healing and anti-inflammatory treatment.

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OBJECTIVE To compare the efficacy and safety of parecoxib and ketorolac tromethamine for perioperative analgesia， and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， VIP， Wanfang Data， Baidu and Google， randomized controlled trials （RCT） about parecoxib （trial group） versus ketorolac tromethamine （control group） for perioperative analgesia were collected from the inception to Jun. 17th， 2022. After screening the literature and extracting the data， the quality of the included literature was evaluated using the bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0. Meta-analysis， sensitivity analysis and publication bias analysis were performed with RevMan 5.4 software. RESULTS A total of 12 RCTs were included， with 1 118 patients. Meta- analysis results showed that at the time of administration before anesthesia induction， there was no statistically significant difference between the 2 groups in visual analogue scale （VAS） [MD＝－0.16， 95%CI （－0.41， 0.09）， P＝0.20]， numerical rating scale （NRS） [MD＝0.01， 95%CI （－0.36， 0.38）， P＝0.97]， postoperative bleeding [MD＝0.15， 95%CI （－0.63， 0.93）， P＝0.71]， and consumption of opioid analgesics [MD＝0.12， 95%CI （－0.77， 1.01）， P＝0.79]. At the time of postoperative administration， VAS and bleeding volume at 48 h after operation of trial group were significantly lower than control group （P＜0.05）. The results of subgroup analysis by different com assessment time points showed that the VAS of patients in trial group at 0 h after operation were significantly lower than control group at the time of administration before anesthesia induction； at the time of postoperative administration， VAS of patients in the trial group at 12 h and 48 h after operation were significantly lower than control group （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups [RR＝0.93，95%CI （0.78，1.11），P＝0.43]. The results of subgroup analysis according to different types of adverse reactions showed that the incidence of nausea and vomiting of trial group was significantly lower than control group， and the incidence of other adverse reactions was significantly higher than control group （P＜0.05）. Results of sensitivity analysis showed that study results were stable and reliable. Results of publication bias analysis showed that there was great possibility of publication bias in this study. CONCLUSIONS The efficacy of parecoxib is equivalent to that of ketorolac tromethamine for perioperative analgesia before operation； at the time of administration after operation， parecoxib has better analgesic effect and less postoperative bleeding； the incidence of nausea and vomiting caused by parecoxib is lower at any time of administration.

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OBJECTIVE: Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac. METHODS: Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N'-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits. RESULTS: Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends. CONCLUSION: The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.

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OBJECTIVE: This research aimed to formulate fast-dissolving sublingual films of Ketorolac tromethamine to improve therapeutic efficacy, patient compliance and overcome the drug's gastrointestinal side effects by avoiding direct contact with the gastric mucosa. METHODS: This research produced Ketorolac tromethamine sublingual film by solvent casting method using a variable ratio of polymer and plasticizer but a fixed quantity of other excipients and solvent ratio to evaluate the effect of these components on the overall formulation. Total 9 (F1 to F9) formulations were prepared where the ratio of Kollicoat®IR as polymer and Polyethylene glycol 400 as plasticizer were 2.0:1, 3.0:1, 4.0:1, 4.0:1, 4.8:1, 5.6:1, 5.33:1, 6.0:1, 6.66:1 respectively. The prepared films were evaluated through morphological and organoleptic properties, weight uniformity, folding endurance, surface pH, thickness, percentage of moisture loss, dispersion, dissolution, and drug content uniformity. Also, API-excipients compatibility was evaluated by FTIR spectroscopy. RESULTS: Formulation-2 (F2) demonstrated better film with optimum folding endurance where the ratio of Kollicoat®IR and Polyethylene glycol 400 was 3.0:1. The film's surface and distribution of polymers and drugs were examined by trinocular microscopic imaging where drug molecule showed uniform distribution which was supported by the assay (100.1%) and content uniformity (100.1 ± 1.97%). Performed dissolution studies showed 99.3% of drug dissolution occurred in just 3 min at pH 6.8. CONCLUSION: Prepared films were found to have thin, fast dispersion and dissolution properties. Therefore, the patients can use the sublingual film to get rapid relief of pain with minimal side effects in the gastrointestinal tract.

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The aim of the current study was to prepare glutamic acid crosslinked poly(itaconic acid/methacrylic acid) microgels for pH-responsive delivery of ketorolac tromethamine, using aqueous free radical polymerization technique. The polymerization of polymer with monomers was carried out by a crosslinking agent N', N'-methylene bisacrylamide in the presence of initiator ammonium persulfate. The prepared microgels were characterized for structure, surface morphology, thermal stability, and crystallinity. Similarly, studies such as sol-gel analysis, drug loading, and polymer volume fraction were performed for the fabricated microgels. The pH-sensitivity of the developed microgels was investigated at three different pH values i.e., pH 1.2, 4.6, and 7.4 by swelling and in-vitro drug release studies. Maximum swelling and drug release were found at pH 7.4 as compared to pH 1.2 and 4.6, which indicated the pH-sensitive nature of the prepared microgels. The toxicity of the prepared microgels was evaluated by cell line and HET-CAM test, which demonstrated no toxic effect of the prepared microgels. In-vivo study was carried out on rabbits and high plasma concentration was reported for the drug loaded microgels as compared to drug solution and commercial product Keten. Hence, the prepared microgel system could be employed as an excellent carrier for the controlled drug delivery system.

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Pulsatile drug delivery systems have drawn attention in contemporary research for designing chronotherapeutic systems. The current work aims to design pulsatile ketorolac tromethamine tablets using compression coating for delayed delivery with a lag time suitable for the treatment of morning stiffness in arthritis. Rapidly disintegrating core tablets of ketorolac tromethamine were formulated using super-disintegrants, and the optimized formulation was compression using PEO WSR coagulant and Eudragit RLPO for delaying the release. The central composite design and response surface methodology were employed to optimize the formulation and process parameters namely PEO WSR Coagulant (X1), Eudragit RLPO (X2), and Hardness (X3). The dependent variables optimized were lag time and time required for 95% drug release. Analysis using response surface graphs and mathematical modeling of the results allowed identifying and quantifying the formulation variables active on the selected responses. A polynomial equation fitted to the data was used to predict the composition with optimum responses. Compression-coated pulsatile tablets' optimized composition exhibited a lag time of 9 h and released 95% of the ketorolac tromethamine in 17.42 h. Validation of the mathematical model assured the reliability of QBD in formulation design. In vivo X-ray imaging and pharmacokinetic studies established a strong relationship between the coated polymers maintaining the desired lag time for delayed delivery of the active to coincide with the chronobiology for enhanced bioavailability at the right time when needed.

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Purpose: This study aimed to observe the application value of dezocine and ketorolac tromethamine in patient-controlled intravenous analgesia (PCIA) of patients undergoing laparoscopic cholecystectomy (LC). Methods: A total of 154 patients who underwent LC surgery in our hospital and received PCIA after surgery from September 2020 to September 2021 were selected, they were divided into group A (n = 77) and group B (n = 77). Group A was given dezocine and group B was given ketorolac tromethamine. The analgesia, sedation, comfort, and adverse reactions of the two groups were closely observed at 4, 8, 12, and 24 h after surgery. Results: At 4, 8, 12, and 24 h after surgery, the visual analog scale scores in group B were lower than those in group A (P < 0.05). At 4, 8, 12, and 24 h after surgery, the Ramsay scores in group B were higher than those in group A (P < 0.05). At 4, 8, 12, and 24 h after surgery, there was no significant difference in Bruggrmann comfort scale scores between the two groups (P > 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Both dezocine and ketorolac tromethamine have high clinical application value in patients who underwent LC surgery and received PCIA, with higher patient comfort and fewer adverse reactions. But compared with dezocine, ketorolac tromethamine can achieve better sedative and analgesic effects, which is worthy of clinical promotion.

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The present study aims to explore the potential function of ketorolac tromethamine in treating osteoarthritis by examining its effects on interleukin-1ß (IL-1ß)-triggered cellular senescence in chondrocytes. More ß-galactosidase (SA-ß-Gal) positively stained cells, promoted cell fraction in the G0/G1 phase, increased release of matrix metalloproteinase (MMP)-3 and MMP-13, and upregulated cellular senescence-related genes (p21 and p53) were observed in IL-1ß-challenged HC-A cells, all of which were significantly reversed by 25 and 50 mg/mL ketorolac tromethamine. Furthermore, the upregulated cyclooxygenase-2 (COX-2) and elevated release of prostaglandin E2 in IL-1ß- challenged HC-A cells were dramatically repressed by ketorolac tromethamine. Lastly, the inhibitory effects of ketorolac tromethamine on the activation of SA-ß-Gal and the upregulation of p21 and p53 were greatly abolished by the overexpression of COX-2. Collectively, ketorolac tromethamine repressed cellular senescence in aging articular chondrocytes by inhibiting COX-2.

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