Study of analytical methods for some calcium channel blocker drugs, from dihydropyridine class

Abstract

The thesis consists of five parts: Part I: General introduction It explained the nature and types of cardiovascular diseases, focusing on calcium channel blockers; their mechanism of action, subtypes and their pharmacological profiles. Also, it dealt with the drug combinations used in treatment of different cardiovascular diseases. Part II: Literature review This part included a general review of physical and chemical properties, pharmacology, and pharmacokinetics of the cited drugs used in combination; Amlodipine (AML), Valsartan (VAL), Hydrochlorothiazide (HCT), Nifedipine (NIF), and Atenolol (AT). Also, some analytical methods, found in the literature, and used for determination of the five drugs either alone, in different combinations, or in combination with each other, were mentioned in this part. Part III: Electrochemical potentiometric determination of Amlodipine; a comparative study This part dealt with the construction of six different ion selective electrode sensors used for determination of Amlodipine either alone, in presence of other interferents found in combination or as fillers in the pharmaceutical dosage form, or spiked in human plasma and urine. It was divided into five sections: Section A: Introduction to ion selective electrode (ISE) technique That summarized the introduction to the two main types of ion selective electrode sensors; ion-exchanger-based ISE and neutral ionophore-based ISE. Section B: Experimental In this section all instruments, chemicals, reagents and standard solutions prepared were discussed together with the general procedures used in fabrication of iron oxide micro-particles and coating of both nano- and micro-particles. Also, it dealt with the construction of Amlodipine ion-exchanger doped sensing membrane electrodes, where three sensors were constructed using the same ion-exchanger, phosphotungstic acid, to precipitate Amlodipine to be incorporated in the membrane. Then, the classical electrode sensor was compared with the other two sensors utilizing the new approach of inclusion of Amlodipine loaded on iron oxide micro- and nano-particles. The three sensors were compared also on the level of determination of Amlodipine in dosage form, and some biological fluids e.g. plasma and urine. The other approach, Amlodipine ionophore-doped sensing membrane electrode, using β-cyclodextrin ionophore in membrane fabrication, was utilized in this section to construct three sensors compared to each other. The classical ionophore-doped sensor was compared to the other two sensors that used Amlodipine loaded micro- and nano-particles of iron oxide on the level of dosage form and biological fluids.

Section C: Results and discussion It summarized all the results and discussions about the six sensors, compared statistically to each other, other similar approaches, and some other reported methods. Part IV: Spectrofluorimetric determination of Amlodipine and Valsartan, in combination This part discussed six spectrofluorimetric methods for simultaneous determination of Amlodipine and Valsartan based on native and synchronous fluorimetry. Section A: Introduction to spectrofluorimetry It dealt with the introduction to different types of spectrofluorimetric methods of analysis. Section B: Experimental It summarized all instruments, chemicals, reagents, and standard solutions used in the whole part. It included the construction of two different methods based on native fluorescence, conventional native fluorescence and single λex method, for simultaneous determination of Amlodipine and Valsartan. The first method used the excitation wavelength for each drug component to determine it in the mixture, and the second method was based on using one excitation wavelength to determine both drugs in only one step. Both methods were validated and compared to some reported methods. Three different methods utilizing the effect of different addiditives to increase method sensitivity of Amlodipine and Valsartan simultaneous determination in single λex method, were discussed. Then, determination of AML and VAL by synchronous spectrofluorimetry with the application of chemometrics, was introduced. Some factors were optimized for enhancing fluorimetric response of fluorophores either native or synchronous e.g. type and volume of solvent (as a sensing agent), pH, selection of excitation wavelength and selection of optimum wavelength difference. Some other additives were studied to increase single λex method sensitivity e.g. different types of surfactants, β-cyclodextrin in different concentrations, and magnetite iron oxide nanoparticles in different concentrations also. Section C: Results and discussion The results of all suggested methods were statistically compared to each other, and to different other reported methods for determination of the same mixture by different techniques. Part V: Spectrophotometric determination of some dihydropyridine combinations Section A: Introduction to spectrophotometry It dealt with the introduction to different types of spectrophotometric methods of analysis that utilize less manipulation steps. Also, a theoretical background about the approaches used, was introduced. Section B: Experimental All instruments, chemicals, standard solutions preparation and reagents were summarized. Successive spectrophotometric resolution technique (SSRT) coupled with constant multiplication (CM) was utilized to obtain the zero order absorption or first derivative spectra of the proposed drugs to simultaneously determine Amlodipine, Valsartan and Hydrochlorothiazide without many manipulation steps. Amplitude center method, Amplitude factor and double divisor ratio spectra derivative method were used to determine the partially or severely overlapped spectra of the proposed drugs, AML, VAL and HCT. Then the application of ratio subtraction technique coupled with constant multiplication (CM), on NIF and AT binary mixture, were discussed. This technique was applied on both zero and first derivative spectra to resolve the partially overlapped spectra of NIF and AT. Also, amplitude factor method was used to determine NIF, and amplitude center method was used for AT determination