Acid and base degraded products of ketorolac

Salaris, Margherita; Nieddu, Maria; Rubattu, Nicola; Testa, Cecilia; Luongo, Elvira; Rimoli, Maria Grazia; Boatto, Gianpiero

doi:10.1016/j.jpba.2010.01.031

Cited by 8 publications

(5 citation statements)

References 2 publications

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“…In pharmaceutical industry, force degradation study has its importance before starting a new formulation, which provides an insight into degradation pathways and impurity of the drug substance also helps in elucidation of the structure of the degraded products. The degradation products of KTR have been identified from the stress degradation study under hydrolysis (acid, base, and neutral), oxidation, photolysis, thermal conditions [13][14][15]. Few computational studies of KTR and its modified derivatives also were reported previously [16,17].…”

Section: Introductionmentioning

confidence: 99%

Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies

Uzzaman

Uddin

2019

DARU J Pharm Sci

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Background Ketorolac (KTR) is used as an analgesic drug with an efficacy close to that of the opioid family. It is mainly used for the short term treatment of post-operative pain. It can inhibit the prostaglandin synthesis by blocking cyclooxygenase (COX). Methods In this investigation, the inherent stability and biochemical interaction of Ketorolac (KTR) and its degradation products have been studiedon the basis of quantum mechanical approaches. Density functional theory (DFT) with B3LYP/ 6-31G (d) has been employed to optimize the structures. Thermodynamic properties, frontier molecular orbital features, dipole moment, electrostatic potential, equilibrium geometry, vibrational frequencies and atomic partial charges of these optimized structureswere investigated. Molecular docking has been performed against prostaglandin H2 (PGH2) synthase protein 5F19 to search the binding affinity and mode(s). ADMET prediction has performed to evaluate the absorption, metabolism and carcinogenic properties.Results The equilibrium geometry calculations support the optimized structures. Thermodynamic results disclosed the thermal stability of all structures. From molecular orbital data, all the degradents are chemically more reactive than parent drug (except K3). However, the substitution of carboxymethyl radicalin K4 improved the physicochemical properties and binding affinity. ADMET calculations predict the improved pharmacokinetic and non-carcinogenic properties of all degradents. Conclusion Based on physicochemical, molecular docking, and ADMET calculation, this study can be helpful to understand the biochemical activities of Ketorolac and its degradents and to design a potent analgesic drug.

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Section: Introductionmentioning

confidence: 99%

Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies

Uzzaman

Uddin

2019

DARU J Pharm Sci

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“…A number of analytical methods have been investigated for the determination of KTL either alone or in its salt form or combination with other drugs, such as liquid chromatography-mass spectrometry (LC-MS/MS) [4], high-performance thin-layer chromatography [5], LC-MS [6], and high-performance liquid chromatography (HPLC) [7][8][9][10][11]. KTL has been determined in blood after a solid-phase extraction by gas chromatography-MS after derivatization using diazopropane [12].…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Determination of Ketorolac - A Non-Opioid Analgesic at Glassy Carbon Electrode

Hanabaratti

Gowda²,

Tuwar

2019

Asian J Pharm Clin Res

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Objectives: The study has been carried to investigate the electro-oxidation mechanism and to develop a selective and sensitive method for determination of ketorolac (KTL), a non-opioid analgesic drug,.Methods: A simple electro analytical method was used for the determination of ketorolac (KTL) using glassy carbon electrode by cyclic and differential pulse voltammetric techniques (DPV). The effect of various experimental parameters such as accumulation time, pH, scan rate, on the voltammetric responses of KTL was evaluated.Results: In the optimized conditions, variation of peak current with respect to concentration was studied and the calibration curve of the peak current vs. KTL concentration was drawn with a linear range of 10- 350 Î¼M with an excellent detection limit of 8.08Ã—10-8 M. This method was successfully tested for the determination of KTL in pharmaceuticals and human urine samples.Conclusion: From the results, it was observed that, the selected method is rapid, sensitive and low cost.

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“…Degradation behavior of KT has been studied by several researchers in the presence of different factors like pH, temperature, oxidant, and light. The acidic, basic and neutral solution of the drug was found to degrade in hydrolytic, photolytic and thermal conditions but the solid form of the drug was found to be stable under photolytic condition [2][3][4][5][6]. Study of the literature suggests that KT being sensitive molecules may not yield stable film formulation when formulated into orally dissolving films using the solvent casting technique.…”

Section: Introductionmentioning

confidence: 99%

Studies on Effect of Formulation and Processing Parameters on Stability of Ketorolac Tromethamine Orally Dissolving Films

Sapkal¹,

Bonde

Gawande

et al. 2019

Int J App Pharm

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Objective: The objective of the proposed work was to study the effect of various formulation and process parameters of solvent casting method on the physical and chemical stability of Ketorolac Tromethamine (KT) in the orally dissolving film dosage form. Methods: KT-excipient interaction study was carried out both in solid state and by processing samples through the solvent casting technique. The samples were evaluated using IR spectroscopy (IR) and X-ray diffractometry (XRD). Solvent casting method was used to prepare KT films using different film-forming polymers, and solvents. The drying temperature and pH of the dispersion were also varied to study the effect of these parameters on the stability of KT. All the formulations were analysed chemically initially and after one month of storage at 40 °C/75% RH. Results: During KT-excipient interaction study in solid state KT was found to be stable. No significant changes were observed in its impurity profile. Interaction between different polymers and KT was observed after the solvent casting process as revealed by IR and XRD analysis. The interaction was further confirmed in the film formulations upon chemical analysis. The polymers showing interaction with KT in XRD and IR were making it unstable chemically and were responsible for its chemical degradation as revealed by chemical analysis. It was also revealed that KT is most stable when processed using water as the solvent. KT was found to be stable when processed at a higher temperature and at acidic pH during film formation. It was found that chemical stability is more when Polyethylene oxide (PEO) and water under acidic pH are used and films are dried at a higher temperature. Conclusion: Both formulation parameters and processing conditions of the solvent casting technique affects the stability of drugs and hence should be studied as part of pre-formulation studies while developing orally dissolving films of drugs.

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Acid and base degraded products of ketorolac

Cited by 8 publications

References 2 publications

Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies

Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies

Electrochemical Determination of Ketorolac - A Non-Opioid Analgesic at Glassy Carbon Electrode

Studies on Effect of Formulation and Processing Parameters on Stability of Ketorolac Tromethamine Orally Dissolving Films

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