Summary:
methods have been developed and evaluated using the High Performance Liquid Chromatography Technique using a photodiode array detector (PDA) for the quantification of brinzolamide and brimonidine tartrate and their impurities in ophthalmic collyrium.
In the theoretical part of the dissertation, the main features for the validation of an analytical method, as well as the acceptance criteria according to ICH, are presented in Chapter 1. The second chapter presents the basic principles for determining the impurities in generic pharmaceuticals and the theoretical background based on the international directives and the legislation that is now very strict. The way of developing a generic pharmaceutical preparation is described in detail compared to the commercially available prototype, and reference is also made to how to calculate impurities limits based on current legislation. The third chapter describes the pharmacological elements of brimonidine brinzolamide and tartrate and their mechanism of action.
The experimental part of the dissertation includes Chapters 4, 5 and 6, of which chapter 4 describes the technique of liquid chromatography developed and validated in order to quantitate the related substances of brinzolamide. Analytical studies are carried out to investigate factors influencing analyte and impurity retention in order to determine optimal chromatographic conditions. Subsequently, the HPLC method was evaluated for its main quality characteristics (linearity, accuracy, precision, robustness), while the limit of detection and the limit of quantification of the method were determined. Stability studies on accelerated degradation conditions were performed. Correspondingly, in Chapter 5, the organology and experimental conditions used to quantitate the two active substances, as well as the quantification of the impurities of brimonidine tartrate by the liquid chromatography technique as an analytical method with common chromatographic assay conditions, are mentioned. The studies conducted to investigate the factors affecting the retention of the two substances and the impurities of brimonidine tartrate are reported to determine the optimal chromatographic conditions. Subsequently, the HPLC method was evaluated for its main quality characteristics (linearity, accuracy, precision, robustness), while the limit of detection and quantification limit of the method for quantification of the related substances of brimonidine tartrate was determined. Stability studies on accelerated degradation conditions were performed. Finally, in Chapter 6 a little reference is made to the role of preservatives in ophthalmic collyriums, as well as to the procedure followed for the production of the ophthalmic suspensions of brinzolamide and brimonidine tartrate.
Keywords:
Brinzolamide, Brimonidine Tartrate, Development of Analytical Method, Quantitative Determination of drug substance, Quantitative Determination of impurities
