Sangeetha, R K (2020) Analytical Method Development for Selected Cardiovascular Drugs and Its Application for Impurity Profiling, Degradation and In Vitro Drug-Drug Interaction studies. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
In the current research work UV Spectroscopy and chromatographic methods were developed for the four drugs namely apixaban, rivaroxaban, ibutilide fumarate and dofetilide. These methods provide the availability of the simple way of analysis with strategic and segmented working procedure adopted. Each of the analytical method is economical, time saving, and easily adaptive. The UV Spectroscopic method for apixaban, ibutilide fumarate and dofetilide is advantageous as there is minimum steps involved the sample preparation, time of analysis and procedure. The HPTLC method developed and validated for the four drugs offers a very selective, sensitive and speedy analysis of the samples. Sensitivity of the method is proven with the results obtained in the nanogram level for the drugs. Among all the three methods, the HPTLC method is highly sensitive . The HPLC method was found to be highly selective that they effectively quantified the selected drugs without any interference of matrix(excipients), impurity or degradants. The isocratic mode of operation is efficient and advantageous with only aqueous &organic solvents used in the mobile phase without any buffer system. There is no reported pharmacokinetics data available till date for ibutilide fumarate. The interaction studies developed and validated is a model for the metabolic pathway of ibutilide fumarate as the rat liver microsomes consists of cytochrome 450 enzymes. The steady state concentration level of ibutilide fumarate when present with verapamil till four hours depicts the interference of verapamil in the metabolic pathway of ibutilide .The results implify a concern on the co-administration of ibutilide fumarate and verapamil. Hence the co administration of ibutilide fumarate and verapamil has to be given serious consideration. The analytical methods developed and validated can be applied for the routine analysis of the drug substance in the bulk and dosage forms. The applications of the methods adopted signifies the stability of the drugs under the degradation conditions. The interaction studies is a basic framework for the valuable results on co-administration of ibutilide fumarate with verapamil during multiple drug therapy. The impurity profiling is a valuable tool for the identification of impurity in drug substance for rivaroxaban and in drug product for dofetilide respectively. IMPACT OF THE STUDY: Analytical methods are the versatile tool for the identification, quantification and structural elucidation of the drug molecules. The spectroscopic and chromatographic methods of analysis developed and validated in this work are simple, time efficient and reliable to quantify the selected drugs. The impurity profiling of rivaroxaban and dofetilide is the sensitive technique to identify the impurity which will affect the potency of the drug. The degradation studies of ibutilide fumarate and dofetilide are useful for proving the stability of these two drugs under various stress conditions. The in vitro drug-drug interaction studies is an insight on how the Ibutilide drug responds to the enzymes present in the liver when co-administered with verapamil. The method developed and validated for the in vitro drug-drug interaction studies of Ibutilide fumarate with verapamil will be useful in the clinical studies of these drugs. The analytical methods developed and validated for the selected drugs can be adopted for the routine quality control of these drugs in bulk and formulations.
| Item Type: | Thesis (Doctoral) |
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| Additional Information: | 22231/2013 |
| Uncontrolled Keywords: | Apixaban, Rivaroxaban, Ibutilide fumarate, Dofetilide, Analytical Method Development, Cardiovascular Drugs, Impurity Profiling, Degradation, In Vitro Drug-Drug Interaction studies. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Subramani R |
| Date Deposited: | 12 Jan 2022 00:20 |
| Last Modified: | 12 Nov 2022 16:17 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/14390 |
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