Caroline Grace, A (2018) Development and Validation of Discerning Analytical Quantification Methods for Some Drugs in Pharmaceutical Dosage Forms. Doctoral thesis, The Tamilnadu Dr.M.G.R. Medical University, Chennai.
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Abstract
The present research work entitled “Development and validation of Discerning analytical quantification methods for some drugs in pharmaceutical dosage forms” presents the research accomplished for the establishment of novel analytical methods for quantification of multi-component and single drug in their pharmaceutical dosage forms. The proposed study comprised of three major parts, which consists of chemometric optimization to develop new method for determination of combination drug, HPLC method development and Ultra-Violet spectrophotometric method development and validation of the developed methods for the estimation of different drugs in pharmaceutical formulations. The chemometric tools of statistical experimental design methodology and derringer’s desirability function were employed to develop a new simultaneous RP-HPLC method for the determination of chlorzoxazone, paracetamol and aceclofenac combination in combined tablet dosage form. The time of analysis, resolution and quality of peaks were concurrently optimized by using the above tools. The experimental design has been utilized during the development of the method to minimize the retention times and maximize the resolution. A total desirability function has been used to evaluate more than one response at a time and optimum condition was found by plotting response graphs. The employed optimization methodology reduced overall assay development time and provided essential information regarding the sensitivity of various chromatographic factors on separation attributes. The method showed higher sensitivity and shorter analysis time and making it feasible to be implemented for routine quality control analysis in a pharmaceutical laboratory. The validation study sustained the selection of the assay conditions by confirming that the assay was specific, accurate, linear, precise, and robust. Therefore, this HPLC method can be used as a routine quality control analysis in a pharmaceutical environment. The results of the study demonstrated the benefit of applying this approach in selecting optimum conditions during assay method development. Hence, it was concluded that experimental design approach is a suitable analytical tool to optimize and to develop a novel HPLC methods from the perspective of time of analysis, cost of analysis and laboratory resources. The second part of the work described about the new HPLC method development and validation for few combination drugs and single drugs in pharmaceutical formulations. An attempt was taken to separate and identify the six known impurities of the drug dapagliflozin in tablet dosage form by RP-HPLC method. The reference standards of impurity-A, B, C, D, E and F were spiked in dapagliflozin sample solution prepared from marketed tablet. In the optimized gradient chromatographic conditions dapagliflozin and the impurities were well separated with resolution greater than 2. The results of validation confirmed that the method was precise and linear, accurate, rugged and robust; LOD and LOQ of impurities were well established. Hence the present method can be adopted to separate, identify and quantify the related impurities of dapagliflozin in pharmaceutical formulations. The application of this method in quality control shall improve the safe use of medicinal products which contain dapagliflozin as an active substance. A novel HPLC method was developed for the simultaneous estimation of levetiracetam and its preservatives in commercial oral liquid dosage form. Based on the method results obtained, it was found that the developed method was accurate, precise and sensitive. The proposed method has an advantage over the published methods62-69; this method can be used for analyzing levetiracetam in presence of the preservatives used in commercial formulation. Because monitoring the limit of preservatives present in any formulation is mandatory. Therefore the suggested method could be conveniently adopted for the routine quality control analysis of Levetiracetam and its preservatives from its marketed oral liquid dosage form. All the proposed HPLC and UV spectrophotmetric methods were successfully developed and validated. The applicability of the methods for the estimation of drug substance in their pharmaceutical formulations was proved. All the method validation parameters of analytical performance were checked as per ICH guidelines and the statistical results (percentage, mean, RSD, percentage difference and recovery percentage) of the methods were within the acceptance criteria. Hence it is concluded that the proposed methods are simple, accurate, precise, specific and sensitive and it can be satisfactorily employed for regular analysis of the preferred drugs in formulations in quality control laboratories and it is proved to be extremely beneficial because of the cost effective, uncomplicated, less time consuming, eco-friendly approach of the developed methods.
| Item Type: | Thesis (Doctoral) |
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| Additional Information: | 55733/2013 |
| Uncontrolled Keywords: | Development and Validation, Discerning Analytical Quantification Methods, Pharmaceutical Dosage Forms, Chlorzoxazone, Paracetamol, Aceclofenac, Serratiopeptidase. |
| Subjects: | PHARMACY > Pharmaceutical Analysis |
| Depositing User: | Subramani R |
| Date Deposited: | 10 Apr 2022 13:16 |
| Last Modified: | 10 Apr 2022 13:18 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/19080 |
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