Ketorolac Research Articles

An integrated paradigm between green analytical chemistry and quality-by-design for robust analysis of alcaftadine and ketorolac tromethamine in aqueous humor via sustainable chromatographic methods

The field of pharmaceutical industry has witnessed the launch of a new co-formulated eye drop, composed of alcaftadine and ketorolac tromethamine, for alleviating allergic conjunctivitis. Such new formulation evokes the need for a sensitive, robust and fast analytical method capable of their quantification in their dosage form, in aqueous humor for pharmaco-kinetics studies as well as in presence of plausible degradation products. In this work, two validated stability-indicating chromatographic methods were developed for alcaftadine and ketorolac assaying with good adherence to values of green analytical chemistry. Drugs stabilities were tested under various stress conditions where drugs showed liability for oxidative degradation only. For the first chromatographic method, an integrated merger between analytical quality-by-design and green analytical chemistry was implemented via a UPLC method coupled with photo-diode array detector. A short C18 analytical column of 100 mm was utilized with mobile phase of ethanol: aqueous solution pH 4.0 containing 0.1% triethylamine (40: 60, by volume). Second method was thin layer chromatographic one using HPTLC silica plates as a stationary phase and a developing system of dichloromethane: ethanol (5:4, by volume). Both methods achieved to selectively quantify the studied drugs with high accuracy and precision without any interference from degradation products or related excipients in eye drops. The methods were also successfully exploited for ALF and KTC assaying in rabbit aqueous humor, with no need for prior extraction procedures, for further pharmacokinetic studies. Finally, usage of green solvents gives us the advantage of applying various evaluation tools to conclude method greenness.

Development and in vitro-in vivo evaluation of ocular insert containing ketorolac tromethamine and moxifloxacin hydrochloride

Development and in vitro-in vivo evaluation of ocular insert containing ketorolac tromethamine and moxifloxacin hydrochloride

Effect of kyron T-134 and crospovidone as a fast disintegrating agent on formulation properties of fast dissolving tablet containing ketorolac and rizatriptan using direct compression method

Background and objective: Fast dissolving tablets (FDTs) are "they are uncoated tablets that are supposed to be placed in the mouth and dispersed quickly before being swallowed" within minutes. This study aimed to formulate and evaluate a combination of ketorolac and rizatriptan as orally fast-dissolving tablets using the most common and easiest method to treat migraine attacks with or without aura. To investigate the effects of various types of diluents and super disintegrants on wetting time, water absorption ratio, disintegration, and dissolution time of combined drugs (ketorolac and rizatriptan) as oral dissolving tablets prepared by direct compression technique. Methods: Pre-formulation experiments were carried out in order to rule out any physicochemical interactions between the two medications (ketorolac and rizatriptan) as well as between each drug and its excipients. Four different formulations of fast-dissolving tablets with different types and ratios of diluents and super disintegrants were created using the direct compression technique in order to improve the formulation. Organoleptic characteristics, weight variation, thickness, friability, hardness, disintegration duration, wetting duration, water absorption ratio, drug content, in-vitro dissolution, stability, and comparison tests have all been characterized. Results: According to FT-IR, the two drugs and excipients exhibit no physicochemical interactions. The ideal formula F4 contains crospovidone and Kyron T-134 at optimal concentrations of 2.5% and 2.5%, respectively, and provides the majority of pharmaceutical drugs to be released within the first five minutes, a strong stability profile, the shortest wetting time with the fastest disintegration time (10 sec), and a pleasant flavor (strawberry flavoring agent). Conclusion: Kyron T-134 with Crospovidone in a (1:1) ratio provided rapid disintegration. Ketorolac tromethamine and rizatriptan benzoate may be made into fast-dissolving oral tablets using Kyron T-134 and Crospovidone. Improving migraine compliance is a reasonable goal.

Simultaneous spectrophotometric and chromatographic determination of Ketorolac and Dexamethasone: Overall assessment regarding environmental Impact, Practicality, and functionality principles

Determination of a drug combination that contains a minor component that is also a poorly UV absorbing analyte represents greet challenges in drug analysis. A fixed-dose ophthalmic combination of ketorolac tromethamine (KET) and dexamethasone sodium phosphate (DEX) (in the ratio of 5:1) is used to relieve post-surgical inflammation and seasonal allergic conjunctivitis due to their analgesic and anti-inflammatory activity. Five spectrophotometric methods and a reversed phase chromatographic separation method were developed and validated for simultaneous determination of both drugs in lab-prepared eye drops. Direct spectrophotometric determination of KET (the major, highly UV absorbing analyte) was achieved from the zero-order UV absorption spectra at 323 nm while DEX (which is the minor, poorly UV absorbing analyte) was quantified after applying several spectrophotometric methods. Either fundamental zero-order spectra or ratio spectra were used, and measurements were done at either single or dual wavelengths. The developed methods were: isosbestic point method, absorption factor method, dual wavelength method, ratio difference UV spectrophotometric method, and simultaneous equation method. The developed spectrophotometric methods determine KET in the linearity range of 2.0–12.0 μg/mL and DEX in the range of 5.0 – 35.0 μg/mL. For accurate spectrophotometric determination of DEX in the ratio of the dosage form, multiple standard addition method was applied. HPLC technique was also applied for separation and quantification of both drugs. Chromatographic separation was attained by using Hypersil ODS-C18 (150 x 4.6 mm, 5 μm) column. The mobile phase was composed of 50 % methanol: 50 % phosphate buffer (pH 2.5). The column compartment was maintained at 25 °C. Flow rate was adjusted at 1.2 mL/min and detection was performed by DAD at 254 nm. The linearity of HPLC method was 5.0–100.0 μg/mL, and 5.0–50.0 μg/mL for KET and DEX, respectively. Simultaneous determination of both drugs was applied to lab-prepared eye drops that contain also benzalkonium chloride as inactive ingredient. The developed methods determined the cited drugs with good and acceptable % recovery. The results of the developed methods and a reported HPLC method were compared using one-way ANOVA test, F-test and student’s t-test at confidence level 95 %, and they show no significant statistical difference. Assessment of greenness of the developed methods in comparison with reported HPLC method was performed using different tools, including analytical eco-scale, GAPI and AGREE. HPLC-EAT was also performed to ensure greenness of developed HPLC method. Moreover, assessment of practicality, applicability, and functionality of developed and reported methods was evaluated by BAGI metric tool and WAC calculator, respectively. The developed methods allow simple, rapid, and accurate analysis of quality control samples that contain KET and DEX.

Efficacy of Ketorolac Tromethamine Diluted Saline Irrigant on Postoperative Sequelae in Patients Undergoing Lower Third Molar Impaction Surgery: A Prospective Clinical Study.

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 tromethaminediluted 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 analysetheefficiencyof ketorolac tromethamine diluted saline solution over normal saline without any drug dilution in reducing postoperative sequelae likepain and swellingafter 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 StatisticalPackage for the Social Sciences (IBM SPSS StatisticsforWindows,IBMCorp., 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 scoresthan 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, weconclude that ketorolac saline (10mg/100mL) was more efficaciousin terms of pain reduction than the regular saline solution in impacted lower third molar surgery.

A Novel Formulation of Ketorolac Tromethamine (NTM-001) in Continuous Infusion in Adults with and without Renal Impairment: A Randomized Controlled Pharmacologic Study.

There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment. Participants (≥ 65years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60-89mL/min for mild and 30-59mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75mg/h continuous intravenous (IV) infusion over 24h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15mg every 6h. There were four treatment periods of 24h 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. 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. NTM-001 was considered safe and well tolerated in this population of participants ≥ 65years, 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.

Revisiting and Updating the Interaction between Human Serum Albumin and the Non-Steroidal Anti-Inflammatory Drugs Ketoprofen and Ketorolac.

Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

Bioinspired Carbon Dots-Based Fluorescent Sensor for the Selective Determination of a Potent Anti-Inflammatory Drug in the Presence of Its Photodegradation Products.

Herein, we synthesized biogenic carbon dots (CDs) with blue-shifted maximum excitation (λex/λem of 320/404 nm) from largely wasted tangerine seeds for the first time via a one-step hydrothermal method. The biogenic CDs exhibit a maximum excitation wavelength that overlaps with the absorption spectrum of ketorolac tromethamine (KETO) at 320 nm. The developed CDs serve as a turn-off fluorescent probe via an inner filter effect (IFE) quenching mechanism. The resulting CDs have high quantum yield (QY) (39% ± 2.89%, n = 5) and exhibited great performance toward KETO over a concentration range of 0.50-16.00 μg/mL with a limit of detection (LOD) = 0.17 μg/mL. The nanoprobe achieved a high % recovery in assaying KETO in tablet dosage form and had not been significantly affected by various interferents including co-formulated and co-administered drugs. The nanoprobe shows selectivity toward KETO, even in the presence of its photocatalytic degradation products. It can effectively investigate the elimination of KETO from aquatic systems and test its stability in pharmaceutical preparations. The developed nanoprobe underwent a comprehensive evaluation of its environmental impact using analytical eco-scale (AES), complex green analytical procedure index (Complex GAPI), and the Analytical GREEnness calculator (AGREE). The sustainability of the developed nano sensor was assessed and compared to the reported metal-based quantum dots probe for KETO using the innovative RGB 12 model, considering 12 white analytical chemistry (WAC) perspectives.

Remote-Controlled Activation of the Release through Drug-Loaded Magnetic Electrospun Fibers

The integration of magnetic nanoparticles within fibrillar structures represents an interesting avenue for the remotely controlled release of therapeutic agents. This work presents a novel drug release platform based on electrospun magnetic fibers (EMFs) combining drugs, magnetic nanoparticles (MNPs) and mesoporous silica nanoparticles (MSNs) for controlled drug delivery via alternating magnetic fields (AMF). The platform was demonstrated to be versatile and effective for hydrophilic ketorolac (KET) and hydrophobic curcumin (CUR) encapsulation and the major response observed for AMF-triggered release was reached using drug-loaded MSNs within the fibers, providing fine control over drug release patterns. The EMFs exhibited excellent inductive heating capabilities, showing a temperature increase of ∆T up to 8 °C within a 5 min AMF pulse. The system is shown to be promising for applications like transdermal pain management, oncological drug delivery, tissue engineering, and wound healing, enabling precise control over drug release in both spatial and temporal dimensions. The findings of this study offer valuable insights into the development of the next generation of smart drug delivery systems, based in multifunctional materials that can be remotely regulated and potentially revolutionize the field of nanomedicine.

Safety and efficacy of ketorolac in improving the prognosis of acute type A aortic dissection patients: a protocol of a randomized, double-blinded, and placebo-controlled study

BackgroundAcute type A aortic dissection (aTAAD) is a critical and life-threatening condition. Previous research has demonstrated that the use of ketorolac not only reduces the progression, incidence, and severity of aortic aneurysms in animal models, but also decreases postoperative mortality and complications in patients undergoing open abdominal aortic aneurysm replacement. However, there is a lack of studies investigating the efficacy of ketorolac in treating aTAAD in humans. Therefore, we conducted a study to evaluate the safety and efficacy of ketorolac in patients with aTAAD. Our hypothesis was that ketorolac treatment for aTAAD patients would meet safety indicators and effectively improve patient prognosis.Methods/designThis study is a single-center, randomized, double-blinded, and placebo-controlled study. A total of 120 patients with aTAAD will be recruited and will be randomized into the ketorolac group and placebo group with a ratio of 1:1. Ketorolac tromethamine 60 mg per 2 ml will be intramuscularly injected within 2 h before surgery, followed by intramuscular injections of 30 mg per 1 ml BID. on the first and second postoperative days in the Ketorolac group, while 0.9% saline will be administered at the same dose, dosage form, and time in the placebo group. This study aims to evaluate the safety and efficacy of ketorolac in improving the prognosis of aTAAD. The primary endpoint is the composite endpoint event concerning drug-related adverse events. Secondary endpoints include drug-related adverse events, laboratory examination of blood, diagnostic imaging tests, clinical biomarkers, etc.DiscussionThis study has been approved by the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number: 2023–197-02). This study is designed to evaluate the safety and efficacy of ketorolac in patients with aTAAD. All participating patients will sign an informed consent form, and the trial results will be published in international peer-reviewed journals.Trial registrationThe Chinese Clinical Trial Registry (http://www.chictr.org.cn) ChiCTR2300074394. Registered on 4 October 2023.

RP-HPLC Method Development and Validation of Moxifloxacin Hydrochloride & Ketorolac Tromethamine in Bulk and its Pharmaceutical Formulation

RP-HPLC Method Development and Validation of Moxifloxacin Hydrochloride & Ketorolac Tromethamine in Bulk and its Pharmaceutical Formulation

Comparing the Effects of Intramuscular Injections of Dexamethasone and Ketorolac Tromethamine on Post-treatment Endodontic Pain: An In Vivo Study.

Pain is the primary reason dental patients seek endodontic therapy. Post-treatment endodontic discomfort is a sequelae of periapical inflammation and anti-inflammatory drugs such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) would be reasonable therapy options. The purpose of this study was to compare and assess the efficacy of intramuscular injections of dexamethasone and ketorolac tromethamine versus placebo in reducing post-treatment endodontic pain in individuals undergoing root canal treatment. Patients diagnosed with symptomatic irreversible pulpitis were selected. Nonsurgical endodontic therapy was carried out in a single visit. After completion of the root canal therapy, the patients were randomly assigned to one of the three groups for intramuscular drug administration. In group 1, 2 ml of sterile saline was administered, in group 2, 1 ml of 4 mg dexamethasone was administered; and in group 3, 1 ml of 30 mg ketorolac tromethamine was administered.Preoperative and postoperative pain intensity was measured by a verbal rating scale. Postoperatively, the incidence and severity ofpain were recorded after four, 24, and 48 hours. All three groups showed a highly statistically significant reduction in pain scores when compared to preoperative levels. At the end of four hours, dexamethasone and ketorolac tromethamine showed highly significant results. Dexamethasone significantly reduced pain after 24 hours when compared to ketorolac and placebo groups. At the conclusion of 48 hours, all three groups experienced a gradual decrease in pain levels. Effective and complete debridement of infected root canal system provides predictable gradual reduction of post-endodontic pain.

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

BackgroundWhile antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy.MethodsControl (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment.ResultsGentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties.ConclusionThe results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

Neurotrophic Keratopathy after wide retinal endolaser and postoperative Ketorolac eye drops: A case series.

We report a series of 5 cases, happened in a period of 5 months, who developed neurotrophic keratopathy (NK) following pars plana vitrectomy (PPV) and retinal endolaser for rhegmatogenous retinal detachment (RRD). In our several decennary experience of surgical center predominantly based on vitreoretinal surgery, we had rare cases of postoperative NK. These recent cases of post-surgical NK happened contextually to our change of postoperative non-steroidal anti-inflammatory drugs (NSAIDs) drops, based on Ketorolac Tromethamine 0.5% eye drops. Five patients with a mean age of 61 ± 7.3 years were treated with one or more PPV with intraoperative peripheral endolaser for RRD. Nobody had previous herpetic keratitis, systemic disease like diabetes mellitus or other predisposing factors for NK. In the postoperative period, all patients received Ketorolac Tromethamine 0.5% eye drops for a mean period of 54 ± 25 days. During follow-up visits they developed NK and they were successfully treated with suspension of Ketorolac eye drops, application of therapeutic contact lens or amniotic membrane patch and topical lubricant therapy. Postoperative Ketorolac eye drops, in patients who underwent PPV with endolaser, may reduce the corneal sensitivity, predispose to epithelial disruption and NK development. Studies are needed to explore the effect of NSAIDs on corneal sensitivity reduction in patient who will undergo PPV and extensive endolaser.

Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies

The study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% w/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro study. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.

Ocular bioanalysis of moxifloxacin and ketorolac tromethamine in rabbit lacrimal matrix using liquid chromatography-tandem mass spectrometry.

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 aShimadzu 8050 LC-MS/MS in electrospray ionization-positive mode and the method was validated per US FDA guidelines. Isocratic separation wasperformed with aWaters Symmetry C18 column using methanol and 0.1% formic acid containing deionized water (85:15, v/v). Results & conclusion: An easy, quickand selective method was established and applied to assess the ocular pharmacokinetic profile of a commercially available formulation containing MOXI and KTR. Based on thepharmacokinetic data, this work describes pharmacokinetics-based dosage regimen calculations and their clinical significance.

Використання деяких нестероїдних протизапальних анальгетиків після проведення хірургічного лікування утрудненого прорізування запізнілих зубів та хронічних одонтогенних гайморитів

Purpose: The aim of the study is to compare the effectiveness of using NSAIDs with the active ingredient – ketorolac tromethamine and nimesulide to eliminate postoperative pain in maxillofacial surgery Methods: Examination was carried out on 198 patients. All experimental patients were divided into 4 groups. The first group included 54 patients with difficult eruption of wisdom teeth, who underwent excision of the hood of soft tissues located above an incompletely erupted wisdom tooth. The second group included 49 patients who underwent atypical removal of a decayed wisdom tooth. The third group included 57 patients with atypical removal of dystopian and ratinized teeth. The fourth group included 38 patients who underwent gentle sinus surgery with local plasty of the oro-antral connection in chronic odontogenic sinusitis. Results: The results of the examination of patients after surgical interventions in the maxillofacial region indicate that the drugs nimesulide and «Ketanov» are highly effective and safe drugs, which we recommend using to eliminate pain and treat inflammatory symptoms. Conclusions: The drug nimesulide is effective after surgical interventions on soft tissues. The drug «Ketanov» has a more pronounced and long-lasting analgesic and anti-inflammatory effect, we recommend its use in extensive operations in the maxillofacial area, which include interventions on soft and bone tissues at the same time. Key words: analgesia, inflammation, difficult wisdom tooth eruption, atypical tooth extraction, retention, dystopia, odontogenic sinusitis, nimesulide, Ketanov.

In vitro and In vivo Interaction of Ketorolac Tromethamine and Cefixime Trihydrate

Drug-drug interaction, a major impediment towards safe and effective pharmacotherapy, often leads to adverse outcome or therapeutic failure if not properly identified. The present study employed a number of in vitro and in vivo methods to conduct a thorough investigation of the interaction potential between ketorolac tromethamine (nonsteroidal anti-inflammatory drug) and cefixime trihydrate (beta-lactam antibiotic). UV-Visible spectrophotometry, FTIR and DSC were carried out to analyze the interaction of ketorolac and cefixime in vitro. UV-visible spectrophotometric study at different pH showed hyperchromic shift and blue shift (hypsochromic shift) in the mixture of the studied drugs compared to ketorolac alone. In contrast, only hyperchromic shift was found in the mixture when compared to cefixime alone. In DSC study, the melting endotherm of ketorolac tromethamine shifted from 169.62°C to 149.99°C in the 1:1 mixture. Again, the FTIR spectrum showed that in 1:1 mixture, the lactam (C=O) band of cefixime trihydrate shifted from 1771.68 cm-1 to 1718.63 cm-1, the amide carbonyl band (-CONH) moved from 1669.45 cm-1 to 1616.4 cm-1 and the -OH band moved from 3296.46 cm-1 to 3397.72 cm-1 which might be indicative of interaction between these two drugs. The in vivo study in rat model was designed to determine whether cefixime has any significant impact on the analgesic activity of ketorolac. In vitro antimicrobial effect was also performed to evaluate the effect of ketorolac on cefixime. The findings from these study suggested that neither ketorolac nor cefixime imparted any deleterious impact on the biological property of each other which might indicate that co-administration of ketorolac and cefixime are therapeutically effective and safe. Dhaka Univ. J. Pharm. Sci. 22(2): 137-146, 2023 (December)

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 μL of BACKT, while the other received 40 μL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Hybrid methods treatments for III and IV grade hemorrhoids

Aim: to evaluate hybrid techniques in patients with stage III and IV hemorrhoids.Patients and Methods: from January 2017 to December 2021, 154 patients with external and internal hemorrhoids of the 3rd and 4th stages were treated at the Moscow Medical Center “ON CLINIC”, including men — 118 (76.6%) and women — 36 (23.4%), aged of 45.8 ± 10.3 (27–72) years. The history of the disease was 8.8 ± 2.2 (5–15) years. All patients underwait transanal dearterialization with mucopexy. With its inefficiency, a hybrid operation technique was performed.Results: all patients were operated under spinal anesthesia in a one-day hospital. Operation time was 38.05 ± 4.7 (27–55) min. Postoperative pain syndrome on the first day was 34.1 (30–40) mm on the VAS scale, due to the elective use of Ketorolac tromethamine, 30.1 ± 1.2 (30–40) mg. By the 5–6th day, the pain syndrome decreased to 24.2 (20–30) mm and 15.3 (0–30) mm. Hospital stay was 24.5 ± 2.3 (21–38) hours. The mean period of disability was 12.8 ± 3.1 (10–14) days. When comparing the clinical results of treatment with a follow-up period of 29.9 months, there was no progression of the disease manifestation.Conclusion: the use of hybrid techniques in the treatment of complex forms of hemorrhoids allows to minimize trauma of the anal canal and to reduce the rehabilitation period.