الفهرس 
Quantitative Determination of Tolnaftate, Its Impurities and Degradation Product in Presence of Methyl ParabenOnly 14 pages are availabe for public view
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Abstract
This Thesis Consisted Of Three Parts, References And A Summary In Arabic. Each Part Includes An Introduction, Literature Review, Descriptive Experimental Work, Results And Discussion For The Studied Drugs And Conclusion.
Part I: Quantitative Determination Of Tolnaftate, Its Impurities And Degradation Product In Presence Of Methyl Paraben
This Part Includes:
Introduction And Literature Review
An Introduction About The Anti-Fungal Drug; Tolnaftate (TF) Was Included Illustrating Its Chemical Structure, Physical Properties, Pharmacological Action And Summary Of The Reported Methods For Its Determination In Pure Form And In Pharmaceutical Formulation Either Alone Or In Combination With Other Drugs.
Section (A): Quadruple Divisor Ratio Spectra Derivative Spectrophotometric Method For Determination Of Tolnaftate, Its Toxic Impurities, Alkaline Degradation Product And Methyl Paraben
In This Section, TF, A Thiono-Ester Anti-Fungal Drug, Was Subjected To Alkaline Hydrolysis To Produce Methyl(M-Tolyl)Carbamic Acid (MTC) And -Naphthol (BN) (TF Impurity A). N-Methyl-M-Toluidine (NMT); TF Impurity D, Was Synthesized And Structurally Elucidated, Along With TF Alkaline Degradation Products, Using IR, H1NMR And MS. Quadruple Divisor Ratio Spectra Derivative Spectrophotometric Method (QD) Was Developed For Quantitative Determination Of TF, By Using Sum Standard Spectra Of Equal Concentrations Of BN, MTC, NMT And MP As (A Quadruple Divisor) For TF Determination, Then The First Derivative Of The Resulted Ratio Spectra, Was Obtained. The Concentrations Of The Other Components, BN, MTC, NMT And MP, Were Determined, Individually, By Similar Procedures To That Of TF. Specificity Of The Method Was Assessed By Its Application For Determination Of TF, BN, MTC, NMT And MP In Different Laboratory Prepared Mixtures. Upon Applying The Proposed Method On Tinea Cure® Cream, The Results Obtained Were Statistically Compared To Those Obtained By Applying The Reported HPLC One, And No Significant Difference Between Them Was Observed.
Section (B): Mean Centering Of Ratio Spectra Spectrophotometric Method For Determination Of Tolnaftate, Its Toxic Impurities, Alkaline Degradation Product And Methyl Paraben
In This Section, Mean Centering Of Ratio Spectra Spectrophotometric Method (MCR) Was Developed. It Depended On Utilizing The Mean Centered Ratio Spectra In Four Successive Steps. The Absorption Spectra Of The Five Studied Components Were Recorded In The Wavelength Range Of 210-350 Nm. The Mean Centered Fourth Ratio Spectra Amplitudes For Each Component Were Used For Its Determination. Specificity Of The Method Was Assessed By Its Application For Determination Of TF, BN, MTC, NMT And MP In Different Laboratory Prepared Mixtures. Upon Applying The Proposed Method On Tinea Cure® Cream, The Obtained Results Were Compared Statistically To Those Obtained By Applying The Reported HPLC One, And No Significant Difference Between Them Was Observed.
Section (C): TLC Densitometric Method For Determination Of Tolnaftate, Its Toxic Impurities And Alkaline Degradation Product In Presence Of Methyl Paraben
In This Section, TLC Densitometric Method Was Developed And Validated For Determination Of TF, BN, MTC And NMT In Presence Of MP In Their Pure Form. It Depended On Separation Of The Studied Components On TLC Silica Gel F254 Plates Using Hexane: Glacial Acetic Acid (8: 2, V/V) As A Developing System And Scanning Wavelength Of 230 Nm. It Was Applied For Determination Of TF In Tinea Cure® Cream And The Results Obtained Were Statistically Compared To Those Attained By Applying The Reported HPLC One With No Significant Difference Between Them.
Section (D): HPLC Method For Determination Of Tolnaftate, Its Toxic Impurities And Alkaline Degradation Product In Presence Of Methyl Paraben
In This Section, HPLC Method Was Developed And Validated For Determination Of TF, BN, MTC And NMT In Presence Of MP In Their Pure Form. It Was Based On Separation Of The Five Components On Eclipse Plus C18 Column. The Mobile Phase Used Was Acetonitrile: Water Containing 1% Ammonium Formate (40:60, V/V), With A Flow Rate Of 1 Ml/Min And Detection Wavelength Of 230 Nm. It Was Applied For Determination Of TF In Tinea Cure® Cream And The Results Obtained Were Statistically Compared To Those Attained By Applying The Reported HPLC One With No Significant Difference Between Them.
Part II: Quantitative Determination Of Hydrocortisone Acetate And Fusidic Acid In Presence Of Their Pharmacologically Active Impurities And Formulation Excipients
This Part Includes:
Introduction And Literature Review
This Part Included An Introduction About Hydrocortisone Acetate (HCA) And Fusidic Acid (FA) Illustrating Their Chemical Structures, Physical Properties, Pharmacological Actions In Addition To Their Pharmacologically Active Impurities; Hydrocortisone (HC) And 3-Ketofusidic Acid (KFA) (FA Metabolite, Impurity And Related Substance), Respectively. It Also Included The Reported Methods For HCA And FA Determination In Their Binary Mixtures Or With Other Drugs Or Their Impurities.
Section (A): Quantitative Determination Of Hydrocortisone Acetate And Fusidic Acid In Presence Of Topical Cream Excipients By Multivariate Calibration Method With Model update
In This Section, Principle Component Regression (PCR) And Partial Least-Squares (PLS) Chemometric Assisted Spectrophotometric Methods Were Developed For Determination Of Hydrocortisone Acetate And Fusidic Acid In Their Binary Mixtures Without Previous Separation. Model update Was Performed To Enable Accurate Determination Of Drugs Under Study In Fusi-Zon® Cream Without Interference from Methyl And Propyl Parabens Excipients And Without Incorporation Of Their Pure Standard Samples In The Initial Calibration Sets. The Proposed Methods Were Compared Statistically To A Reported HPLC Method, And No Significant Difference Was Observed Between Them Regarding Both Accuracy And Precision.
Section (B): Green TLC Densitometric Method For Simultaneous Determination Of Hydrocortisone Acetate And Fusidic Acid In Presence Of Their Impurities And Formulation Excipients
In This Section, Eco-Friendly TLC Densitometric Method Was Developed And Validated For Determination Of HCA, HC, FA And KFA In Presence Of MP And PP. The Proposed Method Depended On Separation Of The Studied Components On TLC Silica Gel, F254 Plates, Using A Developing System Composed Of Ethyl Acetate: Ethanol: Acetone (8: 1: 1, By Volume), With Scanning Of The chromatographic Bands At 230 Nm. It Was Applied For Determination Of HCA And FA In Fusi-Zon® Cream And The Results Obtained Were Statistically Compared To Those Attained By Applying The Reported HPLC One With No Significant Difference Between Them.
Section (C): Green HPLC Method For Determination Of Hydrocortisone Acetate And Fusidic Acid In Presence Of Their Impurities And Formulation Excipients
In This Section, A Greener HPLC Method Than The Reported Methods Was Developed And Validated For Determination Of HCA, HC, FA, KFA, MP And PP In Pure Form. It Was Based On Separation Of The Six Components On Xbridge® C8 Column Using Isocratic Mode And A Flow Rate Of 1.8 Ml Min-1 With A Mobile Phase Composed Of Methanol: Water (50:50, By Volume) And Detection At 230 Nm. The Developed Method Was Applied For Determination Of HCA And FA In Fusi-Zon® Cream. The Obtained Results Were Statistically Compared To Those Attained By Applying The Reported HPLC One With No Significant Difference Between Them. The Greenness Profile Of The Proposed Method Was Favorably Compared To Other Reported Methods.
Part III: Quantitative Determination Of Metformin Hydrochloride And Glibenclamide In Presence Of Their Potential Impurities
This Part Includes:
Introduction And Literature Review
This Part Included An Introduction About Metformin Hydrochloride (MFH) And Glibenclamide (GLB) Describing Their Chemical Structures, Physical Properties, Pharmacological Actions In Addition To MFH Toxic Impurity; Melamine (MLM), And GLB Pharmacopoeial Impurities A And B (GIA And GIB). It Also Illustrated The Reported Methods For MFH And GLB Determination In Pure Form And Their Pharmaceutical Formulation, Either In Their Binary Mixture Or In Combination With Other Drugs Or Impurities.
Section (A): Quantitative Determination Of Metformin Hydrochloride And Glibenclamide In Their Binary Mixture By Spectrofluorimetric Method
In This Section, A Fluorimetric Method Was Introduced For Determination Of MFH And GLB In Their Binary Mixture. It Was Based On Measuring The Native Fluorescence Intensity Of GLB At Λemission = 348 Nm, After Excitation At Λexcitation = 226 Nm And Measuring The Fluorescence Intensity Of The Fluorescent Product Produced from The Derivatization Of MFH Using 9, 10-Phenanthraquinone In Alkaline Media At Λemission = 416 Nm After Excitation At Λexcitation = 240 Nm. Optimization Of The Different Experimental Parameters Was Performed. The Developed Method Was Successfully Applied For Determination Of MFH And GLB In Laboratory Prepared Mixtures And Pharmaceutical Formulation And The Results Obtained Were Statistically Compared To Those Of The Reported HPLC Method With No Significant Difference Between Them
Section (B): Eco-Friendly TLC-Densitometric Method For Simultaneous Determination Of Metformin Hydrochloride, Its Toxic Impurity, Glibenclamide, Its Pharmacopoeial Impurities.
In This Section, Eco-Friendly TLC-Densitometric Method Was Developed And Validated For Determination Of MFH, MLM, GLB, GIA And GIB. The Five Components Were Separated On TLC Silica Gel F254 Plates Using Eco-Friendly Developing System Of Ethyl Acetate: Ethanol: Methanol: Ammonia Solution: Formic Acid (6: 4: 0.5: 0.2: 0.1, By Volume) With Detection At 235 Nm. It Was Also Applied For Determination Of MFH And GLB In Glucovance® Tablet And The Results Obtained Were Statistically Compared To Those Attained By Applying The Reported HPLC One With No Significant Difference Between Them Regarding Both Accuracy And Precision.
Section (C): Eco-Friendly HPLC Method For Simultaneous Determination Of Metformin Hydrochloride, Its Toxic Impurity, Glibenclamide And Its Pharmacopoeial Impurities
In This Section, An Eco-Friendly HPLC Method Was Developed And Validated For Determination Of MFH, MLM, GLB, GIA And GIB. The chromatographic Separation Occurred On Xbridge® C18 Column With Eco-Friendly Mobile Phase Using Gradient Elution Mode And Detection Was Set On 235 Nm. Method Utility Was Verified By Its Application For Determination Of MFH And GLB In Glucovance® Tablet. The Proposed Method Was Favorably Statistically Compared To The Reported HPLC One, With No Significant Difference Between Them.
This Thesis Contains 131 References, 89 Figures, 70 Tables And An Arabic Abstract.