الفهرس 
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Abstract
This thesis consists of five parts in addition to the references and a summary in Arabic. Each part includes an introduction, literature review, descriptive experimental work for the studied drugs, results and discussion.
Part I: Quantitative Determination of Diclofenac Na and Diflunisal in Their Binary Mixtures and Pharmaceutical Formulation
This part consists of five sections.
Section (A): Introduction and Literature Review
This section includes an introduction about the pharmacological actions of Diflunisal (DIF) and Diclofenac Na (DIC), their chemical structures, physical properties and summary of the published methods developed for their analysis in their single form and in their binary mixture.
Section (B): Determination of Diclofenac Na and Diflunisal by Dual Wavelength Spectrophotometric Method
In this section, dual wavelength Spectrophotometric method has been developed and optimized for simultaneous analysis of DIF and DIC using their zero order spectra. The principle for dual wavelength method is that the absorbance difference at two points on the spectra is directly proportional to the concentration of the component of interest, independent of the interfering component.
Absorbance values of DIF were the same at 287 and 308.8 nm, so that these wavelengths were selected for determination of DIC. The same as for 253.6 and 308.8 nm, the absorbance values of DIC were the same and hence those two wavelengths were selected for estimation of DIF
The developed method was successfully applied for quantitation of the studied drugs in laboratory prepared mixtures and in Rhumafen forte® suppositories, the standard addition technique has been applied to verify their validity.
Section (C): Determination of Diclofenac Na and Diflunisal by Q-Analysis (Graphical Absorbance Ratio) Method
In this section, Q-Analysis method was developed for simultaneous determination of of DIF and DIC. In this section two wavelengths should be carefully selected, one of the two selected wavelengths is the isoabsorptive point and the other is the wavelength of maximum absorption of one of the two components. Using the absorbance values at 268 nm (λ iso) and 226.6 nm (λ max for DIF) gave the best results regarding selectivity. The developed method was successfully applied for quantitation of the studied drugs in the range of 2-10 µg mL-1 , also it was used for their determinatiom in different laboratory prepared mixtures and in pharmaceutical formulations.
Section (D): Determination of Diclofenac Na and Diflunisal by Mean Centering of Ratio Spectra Spectrophotometric Method
A simple Spectrophotometric method was developed for determination of the studied mixture without prior separation steps. In this method, the mean centered of ratio spectra amplitudes at 309 nm was used for quantitation of DIF and DIC. The absorption Spectra in the wavelength range of 250-350nm were used and Spectra of standard 4 and 3
µg mL-1 of pure DIC and DIF were used as divisors. Good results were obtained when the developed method was applied for quantitation of the studied drugs in laboratory prepared mixtures and in pharmaceutical formulations, Rhumafen forte® suppositories, the standard addition technique has been applied to verify their validity.
Section (E): Determination of Diclofenac Na and Diflunisal by TLC-Densitometric Method
This section is concerned with the development of sensitive, economic and specific TLC-Spectrodensitometric method for determination of DIF and DIC in their bulk powder and pharmaceutical formulations. The studied components were well separated using hexane: ethyl acetate : acetic acid (50: 48: 2, by volume) as a developing system and the separated bands were scanned at 280nm.
Linear relationships were obtained between the mean integrated peak area (× 10-4) and the corresponding concentrations of DIF and DIC in the concentration range of 2 - 10 µg/band. The developed TLC-Densitometric method was successfully applied for quantitation of the studied drugsin Rhumafen forte® suppositories, the standard addition technique has been applied to verify their validity
Part II: Quantitative Determination of Diclofenac Na and Lidocaine HCl in Their Binary Mixture and in Pharmaceutical Formulation
This part consists of four sections.
Section (A): Introduction and Literature Review
This section includes an introduction about the pharmacological actions of Diclofenac Na (DIC) and Lidocaine HCl (LID), their chemical structures, physical properties and summary of the published methods developed for their analysis in their single form and in their binary mixture.
Section (B): Determination of Diclofenac Na and Lidocaine HCl by Ratio Subtraction Spectrophotometric Method
In this section, ratio subtraction (RS) method has been applied for determination of LID using methanol as a solvent. LID concentrations were determined by measuring the absorbance value at its λ max (203 nm) using RS method, while DIC concentrations were determined directly by measuring the absorbance at its λ max (282 nm) using zero order spectrophotometric method.
Specificity of the method was tested by application to different synthetic mixture and good results were obtained. On the other hand, accuracy was verified by application of standard addition technique where no interference from additives were found.
Section (C): Determination of Diclofenac Na and Lidocaine HCl by Mean Centering of Ratio Spectra Spectrophotometric Method
Mean centering of ratio spectra was developed and validated for selective determination of DIC and LID.
In this method, the mean centered of ratio spectra amplitudes at 245,223.2 nm were used for quantitation of DIC and LID, respectively. The developed method was successfully applied for quantitation of the studied drugs in laboratory prepared mixtures and in pharmaceutical formulations, application of standard addition technique assessed method validity.
Section (D): Determination of Diclofenac Na and Lidocaine HCl by TLC-Densitometric Method
This section is concerned with the development of sensitive, economic and specific TLC-Densitometric method for determination of DIC and LID in their bulk powder and pharmaceutical formulations. The studied components were well separated using ethyl acetate : chloroform: methanol: ammonia(5: 3.3: 1.5:0.2, by volume) as a developing system and the separated bands were scanned at 203nm.
Linear relationships were obtained between the mean integrated peak area (× 10-4) and the corresponding concentrations of DIC and LID in the concentration range of 4 – 40,1-10 µg/ band,respectively. The developed TLC-Densitometric method was successfully applied for quantitation of the studied drugs in pharmaceutical formulations, good results were obtained.
Part III: Quantitative Determination of Lidocaine HCl and Cetylpyridinum Chloride in Their Binary Mixtures and in Pharmaceutical Formulations
This part consists of four sections.
Section (A): Introduction and Literature Review
This section includes an introduction about the pharmacological actions of Lidocaine HCl (LID) and Cetylpyridinum Chloride (CPC), their chemical structures, physical properties and summary of the published methods developed for their analysis in their single form and in their binary mixture.
Section (B): Determination of Lidocaine HCl and Cetylpyridinum Chloride by Dual Wavelength Spectrophotometric Method
In this section, dual wavelength method has been developed and optimized for simultaneous analysis of LID and CPC using their zero order spectra. Absorption values of CPC were the same at 208.4 and 216 nm, so that these wavelengths were selected for the determination of LID. The same as in 260.6 and 365.8 nm, the absorbance values of LID were the same and hence those two wavelengths were selected for estimation of CPC
The method was valid for simultaneous determination of LID and CPC in their combined dosage form. Also , statistical comparison of the results of the proposed method with those of the reported one showed no significant difference.
Section (C): Determination of Lidocaine HCl and Cetylpyridinum Chloride by First Derivative of Ratio Spectra Spectrophotometric Method (DD1)
In this section, first derivative of ratio spectra method (DD1) has been applied for determination of both LID and CPC. Standard spectrum of either 8 µg mL-1 of CPC and 6 µg mL-1 of LID were used as divisors. LID concentrations were determined by measuring the absorbance at (235.4 nm), while CPC concentrations were determined by measuring the absorbance at (269 nm).
The developed method was successfully applied for quantitation of the studied drugs in laboratory prepared mixtures and in pharmaceutical formulations.
Section (D): Determination of Lidocaine HCl and Cetylpyridinum Chloride by TLC-Spectrodensitometric Method
This section is concerned with the development of sensitive, economic and specific TLC-Densitometric method for determination of LID and CPC in their bulk powder and pharmaceutical formulations. The studied components were well separated using chloroform: methanol: aceti acid(7.8: 2: 0.2, by volume) as a developing system and the separated bands were scanned at 245nm.
Linear relationships were obtained between the mean integrated peak area (× 10-4) and the corresponding concentrations of LID and CPC in the concentration range of 5 – 50,2-20 µg/ band ,respectively. The developed method was successfully applied for quantitation of the studied drugs in pharmaceutical formulations containing them, the standard addition technique has been applied to verify their validity
Part IV: Quantitative Determination of Diclofenac Na, Diflunisal , Lidocaine HCl and Cetylpyridinum Chloride in Their Binary Mixtures and Pharmaceutical Formulations
Section (A): Determination of Diclofenac Na,Diflunisal, Lidocaine HCl and Cetylpyridinum Chloride byMultivariate Calibration methods, with application of Model Updating
Multivariate calibration models, PCR and PLS, has been successfully applied for simultaneous determination of DIC and LID. On the other hand, model updating method has been used to determine DIF and CPC in pharmaceutical formulations containing them.
Statistical analysis of the results obtained by the developed models was compared with those of the reported methods showed no significant difference, regarding both accuracy and precision.
Section (B): Simultaneous Determination of Diclofenac Na, Diflunisal, Lidocaine HCl and Cetylpyridinum Chloride RP-HPLC Method
A precise, specific, and accurate RP-HPLC method was proposed for the determination of DIC, DIF, LID and CPC. In this method, a gradient elution of the four components was performed at ambient temperature on ODS column using water(containing 1ml of phosphoric acid and 1ml TEA) and acetonitrile , pH= 2.5 as a mobile phase and UV-detection at 230 nm.
By applying the suggested RP-HPLC method, DIC,DIF, LID and CPC could be quantified in the range of 10 – 100, 10-100, 10-120 and 5-100 µg mL-1, respectively. Statistical comparison of the results obtained by the proposed method and reported methods was carried out. The values of the calculated t and F values are less than the tabulated ones which reveals that there was no significant difference between the methods with respect to accuracy and precision.
Part V: Appendix
This part includes a brief idea about the instruments, solvents and chemicals used in other parts, in addition to the detailed preparation of the solutions used in each part throughout this work.