الفهرس 
Stability indicating assay methods for determination of Dapoxetine HCl in presence of its oxidative degradation product (Dapoxetine-N-Oxide)Only 14 pages are availabe for public view
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Abstract
This Thesis Consists Of Three Parts; Each Part Includes Different Analytical Techniques For The Analysis Of Some Drugs Used In The Treatment Of Some Urogenital Tract Diseases. Each Part Of This Thesis Includes The Introduction And Literature Review And Also The Descriptive Experimental Work. Also References And Summary In Arabic Was Included.
GENERAL INTRODUCTION
This Part Contain General Introduction About The Composition Of The Urogenital Tract For Both Male And Female. Also Summary Of The Main Disorders Which Could Affect The Genital Tract For Male And Female Patient Was Included. Brief Summary For The Two Most Common Patient Complaints Which Come Usually To The Clinic (Fungal Infections Of The Female Genital Organ And Premature Ejaculation In Male) Was Also Discussed.
Part I: STABILITY INDICATING ASSAY METHODS FOR DETERMINATION OF DAPOXETINE Hcl IN PRESENCE OF ITS OXIDATIVE DEGRADATION PRODUCT DAPOXETINE-N-OXIDE
This Part Was Developed And Validated For Introduction Of Simple, Sensitive, selective And Accurate Stability Indicating Spectrophotometric And chromatographic Methods For Determination Of Dapoxetine Hydrochloride (DPX) In Presence Of Its Oxidative Degradation Product Dapoxetine-N-Oxide (DNO). The Most Important Advantage Of The Introduced Work Is That Stability Indicating Methods With Identification And Structure Elucidation Of (DNO) The Degradation Product Of (DPX) Was Developed And Validated For The First Time. (DPX) Was Determined With Different Analytical Methods.
- This Part Includes 3 Sections:
- Introduction And Literature Review
This Introduction Describes The Pharmacological Action Of Dapoxetine Hydrochloride (DPX), Its Chemical Structure, And Physical Properties. This Section Also Includes The Results Of The Stability Study Of (DPX) And Preparation Of Degradation Product. Review Of The Published Methods Developed For The Analysis Of (DPX) Was Also Included.
- Section (A): Stability Indicating Ratio Difference And Second Ratio Derivative Spectrophotometric Methods For Determination Of Dapoxetine Hcl:
In This Section; The Presented Work Aimed To Develop Two Accurate, Simple And Sensitive Spectrophotometric Stability- Indicating Methods For Analysis Of DPX And Its Oxidative Degradation Product DNO With Its Identification By Mass Spectrum. The Ratio Difference Method Gives Best Result When Using 20 µg Ml-1 Of DNO As A Divisor And Measuring Absorbance Difference Between 232 And 245 Nm (ΔA 232 – 245 Nm), While Second Ratio Derivative Method, The Absorption Spectra Of DPX Were Divided By The Absorption Spectra Of 20 µg Ml-1 Oxidative Degradation Product (DNO) As A Divisor where DPX Was Measured At Λ = 242 Nm Without Any Interference Of DNO. DPX Was Found To Be Linear Over The Concentration Range Of 3 – 30 And 3 – 40 µg Ml-1 In Ratio Difference And Second Ratio Derivative Method, Respectively.
- Section (B): Stability Indicating HPTLC Method For Determination Of Dapoxetine Hcl
In This Section, Accurate, Sensitive, selective And Cost Effective HPTLC Method Was Developed, Optimized And Validated For Simultaneous Determination Of Dapoxetine Hcl (DPX) In Presence Of Its Oxidative Degradation Products Dapoxetine-N-Oxide (DNO) In Pure Powder And In Its Pharmaceutical Formulation. The Developed Method Depended On Separation Of DPX from Its Oxidative Degradation Product DNO On TLC Aluminum Plates Pre-Coated With Silica Gel 60 F254 As The Stationary Phase Using Petroleum Ether: Ethyl Acetate: Methanol: Triethyl Amine (3:5:1:0.1, By Volume) As A Developing System And The Separated Bands Were Scanned At 210 Nm. Calibration Curve Were Constructed In The Range Of (0.50-2.80 Μg/Band) For Dapoxetine Hcl (DPX) With Good Accuracy. The Developed Method Was Validated According To ICH Guidelines And Demonstrated Good Accuracy And Precision. The Developed HPTLC Method Could Be Used For Analysis Of The Cited Components Without Any Interference from Pharmaceutical Formulation Excipients.
- Section (C): Stability Indicating UHPLC-DAD Method For Determination Of Dapoxetine Hcl
In This Section, Rapid, Accurate, Cost Effective, Sensitive And selective Ultra-High Performance Liquid chromatographic (UHPLC) Method Was Developed And Validated To Determine Dapoxetien Hcl (DPX) In Presence Of Its Oxidative Degradation Product Dapoxetine-N-Oxide (DNO). The Cited Components Was Separated Using Hypersil Gold C8 Column (1.9 µm, 50 Mm X 2.1 Mm) At Isocratic Elution Of Methanol: 0.05% Aqueous Solution Of Sodium Lauryl Sulphate (Ph=3±0.1 Adjusted By Orthophosphoric Acid) (70:30, V/V) At Flow Rate 0.5 Ml Min-1. Detection Of The Studied Drugs Was Performed At 290 Nm. Calibration Curve Was Constructed And DPX Was Found To Be Linear In Concentration Range (1.00 – 80.00 Μg Ml-1). The Total Analysis Time Was 2 Minutes And The Total Peak Areas Were Used To Quantify The Studied Drug. The Proposed Method Was Successfully Applied For The Analysis Of DPX In Pure And Pharmaceutical Formulation.
Part II: DETERMINATION OF MICONZOLE NITRATE, NYSTATIN AND METRONIDAZOLE SIMULTANEOUSLY AS TERNARY MIXTURE IN THEIR TOPICAL FORMULATIONS
This Part Focused On Developing And Validating Different Simple, Accurate And Sensitive Analytical Methods For Simultaneous Determination Of Miconazole Nitrate (MIC), Nystatin (NYS) And Metronidazole (MET) Either In Pure Or In Their Pharmaceutical Formulations. The Developed Chemometric And chromatographic (HPLC And HPTLC) Methods Were Applied With High Sensitivity And selectivity For Determination Of The Studied Components Simultaneously In Their Topical Formulations (Vaginal Suppositories).
- This Part Includes 3 Sections:
- Introduction And Literature Review
This Introduction Describes The Pharmacological Action Of Miconazole Nitrate (MIC), Nystatin (NYS) And Metronidazole (MET) Their Chemical Structure, Physical Properties And Review Of The Published Methods Developed For Their Analysis In Their Binary And Ternary Mixture.
- Section (A): Partial Least Squares (PLS), Linear Support Vector Regression (SVR) And Orthogonal Projections To Latent Structures (O-PLS/PLS) For Determination Of Miconazole Nitrate, Nystatin And Metronidazole As Ternary Mixture: A Comparative Study
This Work Aims To Introduce Smart Solution For Separation Of This Ternary Mixture Using Cheap And Simple Instruments Like UV Spectrophotometer, Hence The Chemometric Solutions Like The Three Presented Here Could Be Of Choice. This Work Aims As Well To Establish A Comparison Between PLSR, O-PLS/PLS And Linear SVR Chemometric Models Through Analysis Of Different Mixtures Of MIC, NYS And MET As A Case Study; Highlighting The Advantages And Disadvantages Of Each Model. Partial Least Squares Regression (PLSR), Linear Support Vector Regression (SVR) And Orthogonal Projections To Latent Structures (O-PLS/PLS) Are Three Chemometric Models Were Applied For Determination Of Miconazole Nitrate (MIC), Nystatin (NYS) And Metronidazole (MET) As Case Study In Raw Materials And Pharmaceutical Formulations Through Handling UV Spectral Data And A Comparative Study Between The Three Methods Were Established Highlighting The Advantages And Disadvantages Of Each Model. 3 Factors 4 Levels Experimental Design Was Established Resulting In A Training Set Consisting Of 16 Mixtures Containing Different Ratios Of The Studied Components. The Prediction Ability Of The Suggested Models Was Validated By Using An Independent Test Set Consisting Of 8 Mixtures.The Results Obtained By The Proposed Models Indicate Their Ability For Determination Of The Cited Drugs With High Accuracy Using Cost Effective And Simple Instruments As Spectrophotometer. from The Presented Study It Was Found That SVR Model Gives Better Results Than The Other Two Proposed Models.
- Section (B): HPTLC Method For Determination Of Miconazole Nitrate, Nystatin And Metronidazole Simultaneously As Ternary Mixture
In This Section, Accurate, Sensitive, selective And Cost Effective HPTLC Method Was Developed, Optimized And Validated For Determination Of Miconazole Nitrate (MIC), Nystatin (NYS) And Metronidazole (MET) As Ternary Mixture In Pure Form Or In Their Pharmaceutical Formulations. The Proposed Method Was Used For Separation And Analysis Of The Cited Compounds Using HPTLC Aluminum Plates Pre-Coated With 0.25 Mm Silica Gel 60 F254 And Using Ethyl Acetate: Toluene: Methanol: Triethyl Amine: Formic Acid (3:1:7:0.3:0.1, By Volume) As A Developing System. The Separated Bands Were Detected At 215 Nm. Calibration Curves Were Constructed where MIC, NYS And MET Were Found To Be Linear In The Range Of 0.40 – 2.00, 0.40 – 2.20 And 0.40 – 2.00 Μg/Band, Respectively. The Developed HPTLC Method Was Validated According To The ICH Guidelines And It Could Be Used For Analysis Of The Cited Components Without Any Interference from Excipients Found In Their Pharmaceutical Formulations.
- Section (C): RP – HPLC - DAD Method For Determination Of Miconazole Nitrate, Nystatin And Metronidazole As Ternary Mixture
In This Section, HPLC-DAD Method Was Developed And Validated For Simultaneous Determination Of Ternary Mixture Of MIC, NYS And MET In Pure Form And In Pharmaceutical Formulations. Optimum chromatographic Conditions For Separation Of The Cited Mixture Was Achieved With High Accuracy On ZOBRAX Eclipse Plus RP- C8 Column Using Isocratic Elution Of Methanol: 0.05% Aqueous Solution Of Sodium Lauryl Sulphate (40:60, V/V) As Mobile Phase. Flow Rate Was Maintained At 0.8 Ml Min-1. Eluents Were Monitored At A Wavelength Of 220 Nm. Calibration Curves For MIC, NYS And MET Were Constructed And It Was Found To Be Linear In The Range Of 5.00 – 50.00, 4.00 – 50.00 And 4.00 – 40.00 Μg Ml-1, Respectively. The Proposed Method Was Developed And Validated According To The ICH Guidelines.
Part III: DETERMINATION OF MICONZOLE NITRATE AND HYDROCORTISONE IN THEIR TOPICAL PREPARATION
This Part Concerned With Developing And Validating Different Simple, Accurate And Sensitive Spectrophotometric And chromatographic Methods For Simultaneous Determination Of Miconazole Nitrate (MIC) And Hydrocortisone (HDC) Either In Pure Or In Their Pharmaceutical Formulation. The Proposed Methods Were Applied With High Sensitivity And selectivity For Determination Of The Studied Components Simultaneously In Their Topical Formulation.
- This Part Includes 2 Sections:
- Introduction And Literature Review
This Introduction Describes The Pharmacological Action Of Miconazole Nitrate (MIC) And Hydrocortisone (HDC), Their Chemical Structure, Physical Properties And Review Of The Published Methods Developed For Their Analysis.
- Section (A): Spectrophotometric Methods For Determination Of Miconazole Nitrate And Hydrocortisone In Their Binary Mixture
In This Section, Three Accurate, Simple, selective Spectrophotometric Methods Namely Isoabsorptive, Ratio Subtraction And Ratio Difference Methods Were Developed And Validated For Determination Of Miconazole Nitrate (MIC) And Hydrocortisone (HDC). Isoabsorptive Spectrophotometric Method Was Developed For Determination Of (MIC) In Presence Of (HDC) In Which (HDC) Was Determined By Direct Spectrophtometry At Λmax 242.6 Nm. Then (MIC) Was Determined At The Isoabsorptive Point At 231 Nm. For Ratio Subtraction And Ratio Difference; (HDC) Was Determined By Direct Spectrophtometry At Λmax 242.6 Nm. Then (MIC) Was Determined By Ratio Subtraction Method At Λmax 220 Nm While For Ratio Difference Method In Which Absorption Spectra Of (MIC) Were Recorded, Divided By Suitable Divisor Of (HDC) Then Measuring The Absorption Difference At 211 And 230 Nm To Obtain The Corresponding Concentrations Of (MIC). MIC And HDC Were Found To Be Linear In Concentration Range 2-24 And 4-24 Μg Ml-1, Respectively.
Section (B): UHPLC - DAD Method For Determination Of Miconazole Nitrate And Hydrocortisone In Their Binary Mixture
In This Section, Simple, Accurate, Sensitive, selective And Cost Effective UHPLC Method Was Developed And Validated For Simultaneous Determination Of Miconazole Nitrate (MIC) And Hydrocortisone (HDC) Either In Pure Or In Their Pharmaceutical Formulation. The Optimum chromatographic Separation Was Achieved With High Accuracy, Symmetry And Precision On Hypersil Gold C18 Column (1.9 µm, 50 Mm X 2.1 Mm) Using Isocratic Elution Of Acetonitrile And Water (30:70, V/V). Flow Rate Was Maintained At 0.4 Ml Min-1 And Eluent Was Monitored At 230 Nm. The Total Analysis Time Was Less Than 2 Min. Calibration Curves Were Constructed And It Were Found To Be Linear In Concentration Range 2 – 50 And 7 – 45 Μg Ml-1 For MIC And HDC, Respectively. The Proposed Method Has Been Successfully Applied For Determination Of MIC And HDC In Bulk And In Their Pharmaceutical Formulation.
This Thesis Refers 70 References; Contain 52 Figures And 48 Tables And Ends With A Summary In Arabic.