الفهرس 
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Abstract
SUMMARY
The present thesis includes the analytical studies for the determination of Verdenafil Hydrochloride (erectile dysfunction) and Dapoxetine Hydrochloride (premature ejaculation) in their pure powder or pharmaceutical preparations.
It comprises three chapters:
Chapter I: contains introduction on Verdenafil (VAR), Dapoxetine (DAP) and on the proposed methods for their determination, and also includes literature survey on the methods reported for their determination and on the selected methods for their analysis.
Chapter II: contains the experimental part which includes the materials, preparation of various solutions, apparatus used and general procedures for the developed methods for the determination of VAR and DAP.
Chapter III: contains the results and discussion, which contains the proposed methods for the determination of VAR and DAP in a mixture, which includes four parts:
Part 1: Simple and rapid spectrophotometric methods were developed for the simultaneous determination of VAR and DAP in mixtures which are:
i) Simultaneous equations method: The determinations were carried out at 291.7 and 245.5 nm for VAR and DAP, respectively. This method was
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applied on their pure and pharmaceutical preparation forms and gives good results.
ii) Dual wavelength method: This method was used for the determinations of VAR and DAP at wavelengths (278.1, 298.4 nm) for VAR and (209.8, 217.4 nm) for DAP. The method was applied on their pure and pharmaceutical preparation forms and gives good results.
iii) Derivative spectrophotometric methods: (1D, 2D, 3D, 4D) were applied for determination of VAR and DAP in presence and absence of each other. In the proposed derivative spectrophotometric methods, which used zero-crossing technique, the wavelengths at 247.8, 260.9, 256.1 or 219.4 nm (zero-crossing wavelengths of DAP) and 240.8, 223.1, 248.2 or 240.8 nm (zero-crossing wavelengths of VAR) for 1D, 2D, 3D, 4D, respectively, were chosen as the optimum working wavelengths for the simultaneous determination of VAR and DAP, respectively. from the previous detailed studies, it was found that 1D and 2D methods (at wavelengths 260.9 nm of VAR or at 240.8 nm for DAP in case of 1D and 2D, respectively) were the best derivative spectra for the simultaneous determination of VAR and DAP in a binary mixture where at these points there is no possible overlapping, the analytical signals are well defined and it is possible to expect more accurate and sensitive results. The analytical validations of these methods were included.
iv) Derivative ratio spectrophotometric: In this part first derivative of ratio spectrophotometric (1DD) method was proposed for spectrophotometric determination of VAR and DAP in a binary mixture. The ratio spectra of VAR had been obtained by dividing its absorption spectra by the absorption spectrum of a certain concentration of DAP (16.0 μgmL-1). Similarly, the ratio spectra of DAP had been obtained by dividing its absorption spectra by the absorption spectrum of a certain concentration
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of VAR (20.0 μgmL-1). Then the first derivative of the obtained ratio spectra of VAR and DAP, separately, can be obtained easily using (Δλ=8) for both drugs and scaling factor = 100 for both VAR and DAP. The concentrations of VAR and DAP were determined using 1DD method by measuring the amplitudes at 241.9 and 238.5 nm, respectively, corresponding to maximum wavelengths. The analytical validation of this method was included.
Part 2: Thermal stability and kinetic studies of VAR and DAP. In this part thermal behaviour of VAR and DAP were studied using different techniques such as TGA, DrTGA, DTA and DSC. The results were confirmed using semi-empirical molecular orbital calculations.
Part 3: This part describes the use of NBS as titrant in the potentiometric determination of VAR and DAP in an acidic medium. N-Bromosuccinimide (NBS) is found to react quantitatively with VAR and DAP in sulphuric and perchloric acids media, respectively, when using NBS. The two drugs are titrated potentiometrically in acidic medium with (2×10-3) M NBS as titrant. The titration curves of drug show well-defined S-shaped stoichiometric end point using a pt-electrode as an indicator electrode. The first differential curves, second differential curves and Gran plots were characterized by sharp inflection permits the accurate determination of the end point.
Part 4: VAR and DAP were determined by applying HPLC method as stability indicating method. Several solvent systems were tried to achieve the best separation for the drugs. chromatographic separation of the two drugs was performed on C8 column and UV detection at 230 nm. The
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proposed method was validated for linearity, accuracy, and precision, limit of detection (LOD) and limt of quantitation (LOQ). Linearity, accuracy and precision were found to be acceptable over ranges of 0.05-30, 0.1 - 45 μgmL-1 with a correlation coefficient 1.000 and 0.999 percentage recovery were 100.2 ± 0.53% and 99.95 ± 0.77% for VAR and DAP, respectively, and these method have many advantages of being simple, rapid and accurate.
All the proposed methods for the determination of VAR and DAP were also applied for their determination in bulk and pharmaceutical forms (tablets). It was carried out on the same batch of samples together with the official and reported methods. The results were compared statistically by the Students’s t-test and Variance ratio F-test. The experimental values did not exceed the theoretical one indicating the absence of any significant difference between the methods compared.
The recovery studies indicated that the excipients in the drug forms did not interfere in the determination of the drug.
Summary: both Arabic and English summary are given by the end of the thesis.
References: contains all references used in the thesis which were of a great help to this study