Object
Title: Analytical quality assessment of selected NSAIDs used in veterinary pharmacotherapy
Abstract:
Nonsteroidal anti inflammatory drugs (NSAIDs) are one of the most frequently used groups of drugs in the world. Their chronic use is associated with side effects, mainly from the digestive system. The solution to this problem was to be a new group of drugs selective COX 2 inhibitors, coxibs. Thanks to their selectivity, these drugs damage the gastric mucosa to a lesser extent while having equally strong anti inflammatory and analgesic effects. However, the development of mentioned group of drugs has been suspended after reports of cardiotoxicity of its representatives during randomized clinical trials. For this reason, valdecoxib and rofecoxib were withdrawn from s ale, and the use of other coxibs in humans was significantly reduced. There is also a strong demand for painkillers and anti inflammatory drugs in veterinary medicine, especially in the course of degenerative joint diseases or conditions after surg ery Coxibs limited to human use have been successfully used in veterinary treatment (e.g. firocoxib, cimicoxib, robenacoxib). Another way to manipulate prostaglandin E2 (PGE2) mediated inflammation is to use prostaglandin (EP) receptor modulation. This resulted in the introduction of a new, non COX inhibiting representative of anti inflammatory drug s into veterinary medicine grapiprant. The subject of the undertaken research was the analytical assessment of the quality of ; NSAIDs used in veterinary therapy on the example of repr e sentatives of the coxib (robenacoxib, cimicoxib, firocoxib) and piprants (grapiprant) group s. The selected drugs are relatively new and have great therapeutic potential, while information on veterinary pharmacotherapy are few and the results of analyzes are often divergent. The main goal of the research was to obtain reliable information on the quality of pharmaceu tical preparations in terms of the content of active substances (API) and the dependencies related to their use. Additionally, the possibility of interactions occurring in the pharmaceutical phase in multidrug mixtures containing the tested NSAIDs was assessed, promoting the breakdown of medicinal substances, and the formation of unfavorable products that may affect the safety of therapy and increase side effects. Indirect research goals included: optimization of analysis conditions for selected compounds (determination of API content and possible impurities); analysis of the durability of medicinal substances and assessment of potential interactions in the pharmaceutical phase with drugs used, e.g. in combined therapy of degenerative diseases, and determining the direction of the changes taking place; preliminary assessment of the toxicity of the analyzed degradation products; modification of the physicochemical properties of coxib, affecting the safety of ; therapy and facilitating the use of the drug. Thin layer chromatography with densitometric detection was used to assess the content and purity of the tested drugs, while the analysis of products and degradation paths was based on the results obtained using ultra high performance liquid chromatography coupled with tandem mass spectrometry. Methods for the determination of selected drugs (grapiprant, celecoxib, etoricoxib, cimicoxib, robenacoxib and firocoxib) were developed and validated and their usefulness was demonstrated in extensive qualitative and quantitative studies and their usefulness was demonstrated in extensive qualitative and quantitative studies and stability tests.and stability tests. In addition, the durability of API and the directions of changes under In addition, the durability of API and the directions of changes under stress stress conditions were analyzed;conditions were analyzed; the formation of additional products was confirmed and their probable the formation of additional products was confirmed and their probable structures were presented.structures were presented. Changes in the degradation rate and durability of coxibs vary Changes in the degradation rate and durability of coxibs vary depending on concomitant medications.depending on concomitant medications. Additionally, preliminary research was undertakenAdditionally, preliminary research was und ; ertaken on the modification of physicochemical properties (using the example of celecoxib) by formingon the modification of physicochemical properties (using the example of celecoxib) by forming an inclusion complex with an inclusion complex with ββ--cyclodextrin, and the possibility of local drug administration by slow cyclodextrin, and the possibility of local drug administration by slow release from titanium dioxide nanostrucrelease from titanium dioxide nanostructures located in on titanium surfacestures located in on titanium surfaces was presentedwas presented. . The results The results obtained obtained as part of the as part of the conducted conducted experiments significantly expand the state of current experiments significantly expand the state of current knowledge in the broadly understood subject of NSAIDs used in veterinary therapyknowledge in the broadly understood subject of NSAIDs used in veterinary therapy,, and outlined and outlined further research directions.further research directions. The results of the conducted analyses, apart from their scientific The results of the conducted analyses, apart from their scientific value, may also bring application possibilities, defining a new direction that will allow to optimize value, may also bring application possibilities, defining a new direction that will allow to optimize pharmacotherapypharmacotherapy,, improve ; the safety of therapy and reduce drug side effectsimprove the safety of therapy and reduce drug side effects.
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Rada Dyscypliny Nauki farmaceutyczne
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Last modified:
Dec 20, 2024
In our library since:
Oct 8, 2024
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8
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0
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http://dl.cm-uj.krakow.pl:8080/publication/5163
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| Edition name | Date |
|---|---|
| ZB-140517 | Dec 20, 2024 |
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