الفهرس 
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Abstract
This Thesis Consists Of Three Parts: Part I Represents General Introduction And Literature Review About All Studied Drugs And Another Two Parts Include An Introduction And Descriptive Experimental Work; In Addition To References And Summary In Arabic.
Part I: General Introduction And Literature Review
This Introduction Describes The Pharmacological Action Of The Drugs Under Study In The Thesis, Their Chemical Structure, Physical Properties And Review Of The Published Methods Developed For Their Analysis.
Part II: Spectrophotometric Determination Of Some Respiratory Drugs
Section (A): Dual Wavelength Spectrophotometric Method For Determination Of Guaifenesin And Theophylline In Their Binary Mixture.
This Section Describes A Simple, Rapid And Cost Effective Dual Wavelength Spectrophotometric Method For Determination Of GUI And THP In Their Binary Mixture.
The Principle Of Dual Wavelength Method Is The selection Of Two Wavelengths where The Interfering Component Shows The Same Absorbance Value And The Component Of Interest Shows Significant Difference In Absorbance With Concentration. selection Of Suitable Wavelengths Plays An Important Role With Respect To selectivity And Sensitivity; Hence Different Wavelengths Were Tried But The Best Results Regarding selectivity And Sensitivity Were Obtained By Using The Absorbance Difference Values At 224.6 Nm And 254.4 Nm For Determination Of GUI where THP Has Zero Absorbance Difference And Using Absorbance Difference Values At 236 Nm And 275 Nm For Determination Of THP where GUI Has Zero Absorbance Values.
Section (B): Ratio Difference (RD) Spectrophotometric Method For Determination Of Guaifenesin And Theophylline In Their Binary Mixture.
In This Section Ratio Difference (RD) Spectrophotometric Method Is Developed And Validated For Determination Of Theophylline And Guaifenesin In Their Binary Mixture. Absorption Spectra Of Each Drug Were Recorded, Divided By Suitable Divisor Then Measuring The Absorbance Difference At 236 Nm And 270 Nm And At 228 Nm And 255 Nm To Obtain The Corresponding Concentrations Of THP And GUI, Respectively.
Section (C): Mean Centering Of Ratio Spectra (MCR) Spectrophotometric Method For Determination Of Guaifenesin And Theophylline In Their Binary Mixture.
In This Section Mean Centering Of Ratio Spectra (MCR) Spectrophotometric Method Is Developed And Validated For Determination Of Theophylline And Guaifenesin In Their Binary Mixture. Absorption Spectra Of Each Drug Were Recorded, Divided By Suitable Divisor And The Obtained Ratio Spectra Were Mean Centered. The Concentrations Of The Two Drugs Were Then Determined from The Calibration Curves Obtained By Measuring Amplitudes At 281.4 And 227.4 Nm For THP And GUI, Respectively.
Section (D): Partial Least Squares And Spectral Residual Augmented Classical Least-Squares Chemometric Models For Determination Of Guaifenesin And Theophylline In Presence Of Guaiacol (Guaifenesin Impurity): A Comparative Study
The Work Introduced In This Section Aims To Compare Two Different Chemometric Methods Namely, Partial Least Squares Regression (PLSR) And Spectral Residual Augmented Classical Least Squares (SRACLS) where The Study Presented Aims To Show The Underlying Algorithm For Each And Introduce A Modest Comparison Between Them To Indicate The Advantages And Disadvantages Of Each. The Comparison Is Conducted On A Pharmaceutical UV Dataset Of Neo Minophylline ® Syrup As A Case Study, where GUI And THP Are Analyzed In Presence Of GUI Impurity.
A 4 Level 3 Factor Calibration Design Was Performed; Resulting In 16 Mixtures For The Training Set Containing Different Ratios Of Interfering Species. An Independent Test Set Consisting Of 8 Mixtures Was Used To Validate The Prediction Ability Of The Suggested Models. The Results Presented Indicate That PLSR Is Considered The De-Facto Standard In Chemometrics And Mostly Used In Several Routine Applications And Is Usually Used In Industry. It Gives Comparable Results To Reference HPLC Methods, Though Handling Traditional UV Data.
Finally, The Proposed PLSR Model Was Successfully Applied For Determination Of THP And GUI In Neo Minophylline® Syrup But SRACLS Could Not; Moreover It Have Advantage Over Reported Methods In That It Can Determine THP And GUI In Presence Of GUI Impurity.
Part III: chromatographic Determination Of Some Respiratory Drugs
Section (A): Determination Of Guaifenesin And Theophylline Or Salbutamol Or Dextromrthorphan Hbr In Presence Of Guaifenesin Impurity (Guaiacol) By HPTLC Method
Simple, selective And Sensitive High-Performance Thin Layer chromatographic (HPTLC) Method Has Been Developed And Validated For The Simultaneous Determination Of Guaifenesin (GUI) And Its Impurity Guaiacol (GUA), In Three Ternary Mixtures With Theophylline (THP) Mix.I Or Salbutamol Sulfate (SAL) Mix II Or Dextromethorphan Hbr (DEX) Mix III. The Separation Was Carried Out On HPTLC Silica Gel 60 F254 Using Ethyl Acetate: Hexane: Methanol: Ammonia (65:35:10:2, By Volume) For Mixture (I) Containing GUI, THP And GUA, And Ethyl Acetate: Hexane: Methanol: Ammonia (65:35:15:2, By Volume) For Mixture (II) Containing GUI, SAL And GUA And Ethyl Acetate: Hexane: Methanol: Ammonia (65:35:5:2, By Volume) For Mixture (III) Containing GUI, DEX And GUA As A Developing System To A Distance Of About 9 Cm. The Plates Were Dried In The Air At Room Temperature, The Bands Were Detected Under UV Lamp And Scanned At 275 Nm For Mixture (I) And (III) And 227nm For Mixture (II). Calibration Curves Were Constructed In The Range Of 0.4 - 2 µg/Band For Both THP And GUI, And 0.4 - 1.2 µg/Band For GUA For Mixture (I), 0.2 – 4 µg/Band, 0.2 – 2 µg/Band And 0.4 - 1.2 µg/Band For GUI, SAL And GUA, Respectively For Mixture (II) And 0.4 - 2 µg/Band, 0.2 – 2 µg/Band And 0.4 - 1.2 µg/Band For GUI, DEX And GUA, Respectively, For Mixture (III) With Good Correlation For The Three Mixtures. The Developed Method Was Validated According To ICH Guidelines And Demonstrated Good Accuracy And Precision. The Results Were Statistically Compared To The Reported Methods With No Significant Difference, Indicating The Ability Of Our Method To Be Used For Routine Analysis Of Drug Product.
Section (B): Determination Of Guaifenesin , Theophylline Or Salbutamol And Guaifenesin Impurity (Guaiacol) By HPLC Method.
In This Section, The Resolution Efficiency Of HPLC Technique Is Utilized For Simultaneous Determination Of Two Ternary Mixture Of GUI, THP And GUA (Mixture I) And GUI, SAL And GUA (Mixture II) In Pure Form And In Pharmaceutical Formulation.
For Mixture (I) chromatographic Separation Was Carried Out Using Isocratic Mode On An ODS C18 Column With A Mobile Phase Consisting Of Methanol: Water (Containing 0.1% Triethylamine): Acetonitrile (30:60:10 By Volume) With A Flow Rate Of 0.7 Ml.Min-1 And UV Detection At 275 Nm At Room Temperature Using Run Time Up To 10 Min. The Calibration Plots Were Linear Over The Concentrations Range Of (2 - 25µg.Ml-1), (2 - 37µg.Ml-1) And (0.5 - 10µg.Ml-1) For THP, GUI And GUA, Respectively. For Mixture (II) chromatographic Separation Was Carried Out Using Isocratic Mode On A Hypersil GOLD CN Column With A Mobile Phase Consisting Of 0.05 M KH2PO4 (Containing 0.1% Triethylamine, Adjusted To Ph= 3.7 By Phosphoric Acid): Methanol (60: 40, By Volume) With A Flow Rate Of 0.6 Ml.Min-1 And UV Detection At 275 Nm At 250C Using Run Time Up To 6 Min. The Calibration Plots Were Linear Over The Concentrations Range Of (0.5-20µg.Ml-1), (0.5 - 30µg.Ml-1) And (0.1 – 10 µg.Ml-1) For SAL, GUI And GUA, Respectively. All The Injections Were Run In Three Replicates And The Injection Volume Was 20 Μl And The Total Peak Areas Were Used To Quantify The Studied Components. The Proposed Methods Were Validated According To ICH Guidelines. The Results Were Statistically Compared To Those Obtained By A Reported HPLC Methods And No Significant Difference Was Found Regarding Accuracy And Precision.
Section (C): Determination Of Guaifenesin And Dextromrthorphan Hbr And Guaifenesin Impurity (Guaiacol) By UPLC Method
A Highly Sensitive, Accurate And New Precise UPLC Method Was Developed For The Simultaneous Determination Of Guaifenesin (GUI), Dextromrthorphan Hbr (DEX) And Guaifenesin Impurity (Guaiacol GUA). chromatographic Separation Was Carried Out Using Isocratic Mode On A Hypersil GOLD Column With A Mobile Phase Consisting Of 0.05 M KH2PO4 (Containing 0.3% Triethylamine, Adjusted To Ph= 3 By Phosphoric Acid): Acetonitrile (75: 25 By Volume) With A Flow Rate Of 0.3 Ml.Min-1 And UV Detection At 275nm At 250C Using Run Time Up To 4 Min. The Separation Was Achieved With The Corresponding Retention Time 0.96, 1.64 And 2.38 Min For GUI, GUA And DEX, Respectively. The Calibration Plots Were Linear Over The Concentrations Range Of (2 - 40µg.Ml-1), (0.5 - 40µg.Ml-1) And (0.5 - 15µg.Ml-1) For DEX, GUI And GUA, Respectively. The Proposed Method Was Validated According To ICH Guidelines. The Results Were Statistically Compared To Those Obtained By A Reported HPLC Method And No Significant Difference Was Found Regarding Accuracy And Precision.
This Thesis Refers 124 References; Contain 38 Figures And 40 Tables And Ends With A Summary In Arabic.