الفهرس 
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Abstract
This thesis consist of four parts which are; general introduction and literature review and three parts each part include descriptive experimental work for the studied drugs in addition to references and Arabic summery.
Part I: General Introduction and Literature Review
This part discusses introduction to the drugs containing carbonyl group, chemical structure, physical properties, pharmacology and published methods for determination of the studied drugs.
Part II: DeterminationofDiflunisaland its impurity (Biphenyl-4-ol)
This part includes 4 sections:
Section A: Spectrofluorimetric Method for Simultaneous Determination of Diflunisal and Its Impurity
In this section, a new sensitive, simple, rapid, accurate and precise spectrofluorimetric method was used for determination of diflunisal and its impurity. Determination of diflunisal is based on first derivative spectrofluorimetric method, while its impurity can be determined by zero order spectrofluorimetric method. Diflunisal was measured at zero-crossing wavelength at 394 nm (zero crossing point with its impurity) which was selected for quantification of diflunisal.The impurity was measured directly at 334 nm after excitation at 254 nm, using 0.05 M phosphate buffer (pH 9) as solvent.The analytical signal resulting from first derivative and zero order spectra were measured for diflunisal and its impurity, respectively. The proposed method was effectively applied for analysis of studied drug in its tablet formulation.The results obtained were statistically compared to the reported method revealing high accuracy and good precision.
Section B: TLC-Densitometric Method for the Separation and Determination of Diflunisaland its Impurity
New validated accurate, sensitive and selective method was applied for quantitative determination of diflunisal and its reported impurity whether in bulk powder or in pharmaceutical dosage form. Diflunisal and its impurity were separated on silica gel TLC F254 plates using toluene: acetone: acetic acid (3.5: 6.5: 0.1 by volume) as mobile phase. Scanning of the separated bands was done at 254 nm, over a concentration range of 0.5-3 and 0.1-1.7 µg/band for DIF and its impurity, respectively. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines demonstrating good accuracy and precision. The results were statistically compared to those obtained by reported method and no significant difference was found between them.
Section C: High Performance Liquid chromatographic Method for the Separation and Determination of Diflunisal and its impurity
In this section, a new validated accurate, sensitive and selective method was applied for quantitative determination of diflunisal and its reported impurity whether in bulk powder or in pharmaceutical dosage form, where a mixture of diflunisal and its impurity were separated on reversed phase silica C18 (5 µm, 250 mm and 4.6 mm) column using 0.05M phosphate buffer (pH = 4): acetonitrile (40:60, v/v) as a mobile phase. The components were detected at 254 nm over a concentration range of 5-30 μg/mL and 2-9 μg/mL for DIF and its impurity, respectively. The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared to those obtained by the reported method and no significant difference was found between them.
Section D: Thermoanalytical Investigation of Diflunisal
In this section, a group of techniques was used in which a physical property of diflunisal is measured as a function of temperature while diflunisal is subjected to a controlled temperature program. These techniques include thermogravimetric analysis (TGA), derivative thermogravimetric analysis (DTG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC).
The TGA/DTG curves of DIF show that the drug is thermally decomposed in one step. This step occurs in the temperature range of 195.06-255.88 ºC with the loss of 97.37% which attributed to the loss of (C13H8F2O3) molecule and melting.
The DTA curve exhibits endothermic peaks. The sharp endothermic peak at 211.9 °C is due to the melting of the compound (mp 211 - 213 °C). The sharp endothermic peak at 309.86 °C is attributed to the decomposition corresponding to the first mass loss observed in TGA/DTG thermogram curves
DSC curve of DIF in drug substance exhibited one endothermic peak at 212.83 °C corresponding to the melting point of the pure drug. DSC curve of DIF in drug product showing endothermic peak at 210.80 °C corresponding to the melting point of the pure drug so no interference between the drug and excipient.
Part III: Determination of Rebamibide and Its Impurity (Debenzyolated Isomer of Rebamibide)
Section A: TLC-Densitometric Method for the Separation and Determination of Rebamipide and Its Impurity
Rebamibide(REB) and its impurity (DER) were separated on silica gel TLC F254 plates using chloroform: methanol: ammonia (6:4: 0.3, by volume) as a developing system for 15 min at room temperature. Scanning of the separated bands was done at 254 nm, over a concentration range of 0.1-1.6 and 0.1-2 µg/band for REB and DER, respectively. The developed method was validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared to those obtained by official method and no significant difference was found between them.
Section B: Second Derivative (D2) Spectrophotometric Method for Determination of Rebamibide in Presence of Its Impurity
Second derivative method was applied for determination of REB. This method enables determination of REB at 337.3 nm without any interference of its impurity. The proposed method was validated according to the International Conference on Harmonization (ICH) guidelines and applied for the determination of the studied compound in drug substances and drug product. The results were statistically compared to those obtained by official method and no significant difference was found between them.
Section C: Spectrophotometric Methods Manipulating Ratio Spectra for Determination of Rebamibide and Its Impurity
In this section, three sensitive and selective methods were used for determination of REB and DER. Method A (Ratio Difference Spectrophotometric Method) was based on dividing the recorded spectra of REB solution by the absorption spectrum of 4 μg/mL of DER (as a divisor), while DER spectra were divided by 20 μg/mL REB spectrum. Good linearity was achieved by measuring the difference between amplitudes of the ratio spectra at 254 and 343 nm for REB, and 336 and 247 nm for DER. Method B (Derivative Ratio Spectrophotometric Method) was based on measuring the peak amplitude of first derivative of ratio spectra (1DD) at 260.4 nm for REB and at 263 nm for DER. Method C (Mean Centering of Ratio Spectrophotometric Method) in which recorded absorption spectra of REB and its impurity (DER) were divided by suitable divisor from DER and REB respectively and the obtained ratio spectra were then mean centered. Good linearity was achieved by measuring the peak amplitudes at 255 nm for REB and DER respectively. The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision.
Part IV: Simultaneous Determination of Dexamethasone and Chlorpheniramine Maleate in Their Binary Mixture and in presence of their reported preservatives (methyl and propyl paraben)
Section A: TLC-Densitometric Method for Simultaneous Determination of Dexamethasone and Chlorpheniramine maleate in presence of their reported preservatives
Validated simple, sensitive and selective method was applied for quantitative determination of dexamethasone and chlorpheniramine maleate in presence of their reported preservatives (methyl and propyl paraben) whether in pure forms or in pharmaceutical formulation. Dexamethasone, chlorpheniramine maleate, methyl and propyl paraben were separated on silica gel TLC F254plates using hexane: acetone: ammonia (5.5:4.5:0.5, by volume) as mobile phase and scanning of the separated bands at 254 nm over a concentration range of 0.1-1.7 and 0.4-2.8 µg/band for DEX and CHL, respectively. The proposed methods have advantages over previously reported methods for determination of dexamethasone and chlorpheniramine maleate in being able to detect lower concentrations of main drugs, and show better resolution of interfering preservatives, hence could be more reliable for routine quality control analyses.
Section B: RP-HPLC Method for Simultaneous Separation and Determination of Dexamethasone and Chlorpheniramine maleate and Their Reported Preservatives
In this section validated simple, sensitive and selective method was applied for quantitative determination of dexamethasone and chlorpheniramine maleate and their reported perservatives (metyl and propyl paraben) whether in pure forms or in pharmaceutical formulation. Using RP-HPLC, a mixture of dexamethasone and chlorpheniramine maleate together with the reported preservatives was separated on reversed phase silica C18 (5 µm, 250 mm, 4.6 mm) using acetonitrile: 0.1 M ammonium acetate buffer, pH 3: (40:60 v/v) a mobile phase. The drugs were detected at 220 nmover a concentration range of 5-50 μg/mL, 2-90 μg/mL, 4-90 μg/mL and 7-50 μg/mL for DEX, CHL, MTP and PRP, respectively.
This thesis refers to 115 references; contains 54 figures and 60tabels and ends with summery in Arabic.