الفهرس 
General introduction and literature reviewOnly 14 pages are availabe for public view
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Abstract
This Thesis Includes Three Parts ; Part I Includes General Introduction And Literature Review About The Studied Drugs . Part II And III Represent An Introduction And Descriptive Experimental Work. It Ends With References And A Summary In Arabic.
Part I: General Introduction And Literature Review
This Introduction Includes The Pharmacological Action Of The Studied Drugs , Their Physical Properties , Chemical Structures And Literature Review Of The Reported Methods For Their Analysis.
Part II : Spectrophotometric Methods For Determination Of Some Antidiabetic And Antihypertensive Drug Mixtures
Section A: Quantitative Determination Of Repaglinide , Metformin Hydrochloride And Melamine In Their Ternary Mixture By Double Divisor Second Derivative Ratio Spectrophotometric Method (DDSDR)
In This Section Repaglinide, Metformin Hydrochloride And Melamine Were Determined By Applying Double Divisor Ratio Derivative Spectrophotometric Method (DDSDR) . The Absorption Spectra Of Different Concentrations Of Each Of The Three Components In Their Pure Forms , Their Laboratory Prepared Ternary Mixtures And Their Pharmaceutical Formulation Samples Were Recorded And Divided By The Absorption Spectrum Of The Binary Mixture Of The Other Two Components As A Double Divisor. Second Derivative Of These Ratio Spectra Were Determined And Then Recorded At 327.6 Nm , 338 Nm And 332.8 Nm For Repaglinide, Metformin Hydrochloride And Melamine Respectively.The Proposed Method Was Found To Have Good Linearity In The Concentration Ranges Of 2-20 Μg Ml⁻¹ , 2-25 Μg Ml⁻¹ And 0.5-10 Μg Ml⁻¹ For Repaglinide, Metformin Hydrochloride And Melamine Respectively.
Section B: Quantitative Determination Of Repaglinide , Metformin Hydrochloride And Melamine In Their Ternary Mixture By Ratio Difference Spectrophotometric Method ( R D )
In This Section Repaglinide, Metformin Hydrochloride And Melamine Were Determined By Applying Ratio Difference Spectrophotometric Method (RD).Different Concentrations Of Repaglinide And Metformin Hydrochloride Were Divided By The Normalized Spectrum Of 1μg Ml-1 Of Melamine As A Divisor, Then The Difference In Amplitude Values Were Determined At 231.4 And 247 Nm For Repaglinide And 239.8 And 251.6 Nm For Metformin Hydrochloride. Similarly Different Concentrations Of Melamine Were Divided By The Standard Spectrum Of 15 Μg Ml⁻¹ Of Metformin Hydrochloride As A Divisor , Then Measuring The Amplitude Differences At 204.2 And 215.6 Nm. The Proposed Method Was Also Applied For The Determination Of The Laboratory Prepared Ternary Mixtures And The Pharmaceutical Formulation. The Developed Method Was Found To Have Good Linearity In The Concentration Ranges Of 1-30 Μg Ml⁻¹ , 2-35 Μg Ml⁻¹ And 0.5-10 Μg Ml⁻¹ For Repaglinide, Metformin Hydrochloride And Melamine Respectively.
Section C : Quantitative Determination Of Saxagliptin , Metformin Hydrochloride And Melamine In Their Ternary Mixture By Double Divisor Second Derivative Ratio Spectrophotometric Method (DDSDR)
In This Section Double Divisor Ratio Derivative Spectrophotometric Method (DDSDR) Was Applied For Determination Of Saxagliptin, Metformin Hydrochloride And Melamine. Different Concentrations Of Saxagliptin Were Determined By Dividing Each Absorption Spectrum Of Saxagliptin By The Spectrum Of The Binary Mixture Of The Other Two Components As A Double Divisor (10 Μg Ml⁻¹ Of Each Of Metformin Hydrochloride And Melamine) . Similarly The Spectra Of The Binary Mixture Of (10 Μg Ml⁻¹ Of Each Of Saxagliptin And Melamine) And (10 Μg Ml⁻¹ Of Each Of Saxagliptin And Metformin Hydrochloride) Were Used As Double Divisors For Determination Of Different Concentrations Of Metformin Hydrochloride And Melamine Respectively. Second Derivative Of These Ratio Spectra Were Determined And Then Recorded At 335 Nm , 330 Nm And 329.4 Nm For Saxagliptin, Metformin Hydrochloride And Melamine Respectively. The Suggested Method Was Also Performed For The Determination Of The Laboratory Prepared Ternary Mixtures And The Pharmaceutical Formulation. The Developed Method Was Found To Have Good Linearity In The Concentration Ranges Of 5-35 Μg Ml⁻¹ , 4-40 Μg Ml⁻¹ And 0.5-10 Μg Ml⁻¹ For Saxagliptin , Metformin Hydrochloride And Melamine Respectively.
Section D : Quantitative Determination Of Felodipine , Ramipril And Felodipine Impurity C In Their Ternary Mixture By Double Divisor Ratio Difference Spectrophotometric Method (DD-RD )
In This Section Felodipine , Ramipril And Felodipine Impurity C Were Determined By Applying Double Divisor Ratio Difference Spectrophotometric Method (DD-RD). The Absorption Spectra Of Different Concentrations Of Each Of The Three Components In Their Pure Forms , Their Laboratory Prepared Ternary Mixtures And Their Pharmaceutical Formulation Samples Were Recorded And Divided By The Normalized Spectra Of The Binary Mixture Of The Other Two Components As A Double Divisor, Then The Difference In Amplitude Values Were Determined At 305 And 350 Nm For Felodipine And 210 And 225 Nm For Ramipril . On The Other Hand The Difference In Amplitude Values Were Determined At 240 And 284 Nm For Felodipine Impurity C. The Proposed Method Was Found To Have Good Linearity In The Concentration Ranges Of 5-55 Μg Ml⁻¹ , 5-45 Μg Ml⁻¹ And 5-45 Μg Ml⁻¹ For Felodipine , Ramipril And Felodipine Impurity C Respectively.
Part III : chromatographic Methods For Determination Of Some Antidiabetic And Antihypertensive Drug Mixtures
Section A : Quantitative Determination Of Repaglinide , Metformin Hydrochloride And Melamine In Their Ternary Mixture By HPLC Method
A Simple, Accurate And Reproducible chromatographic Method Has Been Developed For The Quantitative Determination Of Repaglinide, Metformin Hydrochloride And Melamine In Their Pure Forms And Their Pharmaceutical Dosage Forms.
The HPLC Method Used C18 Column (250 X 4.6 Mm X 5μm Particle Size) And A Mobile Phase Consisting Of Acetonitrile : Methanol : 0.01M Sodium Dihydrogen Phosphate Monohydrate Buffer (Ph Adjusted To 3.00 Using Orthophosphoric Acid) (40:30:30 , By Vol) At A Flow Rate Of 1ml/Min For 6 Min Then It Was Increased To 2ml/Min Till 8 Minutes, With UV-Detection At 242 Nm. The Peaks Of The Three Components Were Obtained At 7.2, 5.2 And 3.9 Minutes Respectively. The Proposed Method Was Validated And Successfully Applied To Replitza® Tablets Containing Repaglinide And Metformin Hydrochloride. The Results Were Statistically Compared To A Reported HPLC Method And No Significant Differences Were Found. The Developed Method Was Found To Have Good Linearity In The Concentration Ranges Of 1-10 Μg Ml⁻¹ , 2-20 Μg Ml⁻¹ And 0.5-10 Μg Ml⁻¹ For Repaglinide , Metformin Hydrochloride And Melamine Respectively.
Section B : Quantitative Determination Of Repaglinide , Metformin Hydrochloride And Melamine In Their Ternary Mixture By HPTLC Method
In This Section An HPTLC Method Was Applied For selective Separation And Quantitative Determination Of Repaglinide, Metformin Hydrochloride And Melamine In Their Pure Forms Using Silica Gel Plate 60 F254 As Stationary Phase And Chloroform : Methanol :Acetic Acid (8.5:1:0.5 , By Vol) As A Developing System .The Detection Wavelength Was 240 Nm. The Obtained Rf Values Were 0.77, 0.1 And 0.34 For The Three Components Respectively. The Suggested Method Was Also Validated And Successfully Applied For The Determination Of Repaglinide And Metformin Hydrochloride In Their Pharmaceutical Formulation Replitza® Tablets. The Developed Method Was Found To Have Good Linearity In The Concentration Ranges Of 0.2-1.5 Μg/Band , 1-10 Μg/Band And 0.1-1.2 Μg/Band For Repaglinide , Metformin Hydrochloride And Melamine Respectively.
Section C : Quantitative Determination Of Saxagliptin , Metformin Hydrochloride And Melamine In Their Ternary Mixture By HPLC Method
In This Section Saxagliptin , Metformin Hydrochloride And Melamine Were Simultaneously Determined In Their Pure Forms And Their Pharmaceutical Formulation By Using An HPLC chromatographic Method. The Method Was Applied Successfully Using C18 Column And A Mobile Phase Consisting Of Acetonitrile : Methanol : 0.05M Potassium Dihydrogen Phosphate Buffer (Ph Adjusted To 3.00 Using Orthophosphoric Acid) (15:20:65 , By Vol) At A Flow Rate Of 1ml/Min, With UV-Detection At 210 Nm. The Developed Method Was Validated And Successfully Applied To Kombiglyze XR® Tablets Containing Saxagliptin And Metformin Hydrochloride. The Developed Method Was Found To Have Good Linearity In The Concentration Ranges Of 1-20 Μg Ml⁻¹ , 2-30 Μg Ml⁻¹ And 1-10 Μg Ml⁻¹ For Saxagliptin , Metformin Hydrochloride And Melamine Respectively.
Section D : Quantitative Determination Of Saxagliptin , Metformin Hydrochloride And Melamine In Their Ternary Mixture By HPTLC Method
A Simple And Accurate HPTLC chromatographic Method Has Been Developed For The Quantitative Determination Of Saxagliptin , Metformin Hydrochloride And Melamine In Their Pure Forms And Their Pharmaceutical Dosage Forms.. The Method Used Silica Gel Plate 60 F254 As Stationary Phase And Chloroform : Ethyl Acetate :Formic Acid (6:4:0.04 , By Vol) As A Developing System .The Detection Wavelength Was 210 Nm. The Obtained Rf Values Were 0.69, 0.12 And 0.4 For The Three Components Respectively. The Method Was Found To Be Linear Through Concentration Ranges Of 0.2-2 µg/Band, 0.3-15 µg/Band And 0.1-1.5 µg/Band For The Three Components , Respectively.
Section E : Quantitative Determination Of Felodipine , Ramipril And Felodipine Impurity C In Their Ternary Mixture By A Green HPLC Method
A Validated Green HPLC chromatographic Method Has Been Developed For The Quantitative Determination Of Felodipine , Ramipril And Felodipine Impurity C In Pure Forms And Their Dosage Form Triacor®. The chromatographic Separation Was Performed On C18 Column (250 X 4.6 Mm X 5μm Particle Size) With A Less Toxic Green Mobile Phase Consisting Of Ethanol : Water : 0.05M Potassium Dihydrogen Phosphate Buffer (Ph Adjusted To 2.7 Using Orthophosphoric Acid) (45:35:20 , By Vol) At A Flow Rate Of 1ml/Min, With UV-Detection At 239 Nm . The Method Was Found To Be Linear Through Concentration Ranges Of 2-25 Μg Ml⁻¹ , 2-25 Μg Ml⁻¹ And 1-12 Μg Ml⁻¹ For The Three Components , Respectively.
Section F : Quantitative Determination Of Felodipine , Ramipril And Felodipine Impurity C In Their Ternary Mixture By HPTLC Method
In This Section Felodipine , Ramipril And Felodipine Impurity C Were Separated And Simultaneously Determined By A selective And Sensitive HPTLC chromatographic Method . The Separation Was Carried Out On Silica Gel Plates Using Toluene: Chloroform : Methanol : Formic Acid (3:5:2: 0.05 , By Vol) As A Developing System. The Detection Wavelength Was At 239 Nm. The Obtained Rf Values Were 0.68, 0.23 And 0.49 For The Three Components Respectively. The Studied Method Was Applicable For Analysis Of The Three Components In Their Pure Forms And Their Pharmaceutical Formulation Triacor® Containing Felodipine And Ramipril. The Results Were Statistically Compared To A Reported HPTLC Method And No Significant Differences Were Found. The Developed Method Was Found To Be Linear Through Concentration Ranges Of 0.5-5 µg/Band, 0.1-5 µg/Band And 0.1-2 µg/Band For The Three Components , Respectively.
Section G : Kinetic Study Of Felodipine Degradation By HPLC chromatographic Method Inspecting The Effect Of Three Important Experimental Factors.
This Work Presents A Kinetic Study Of Felodipine Alkaline Degradation Using A Reported
HPLC Method where The Effects Of Drug Concentration , Alkali Concentration And Temperature On The Rate Of Degradation Are Tested . The HPLC Method Uses C18 Column And A Mobile Phase Consisting Of Tetra Butyl Ammonium Hydrogen Sulphate And Acetonitrile (18:82) With A Flow Rate Of 1.2 Ml / Min At 237 Nm .The Degradation Of Felodipine Was Found To Follow Pseudo-First order , With A Degradation Rate Constant Of 0.0719 Mol /H And A Half Life Of 9.638 Hours . The Effect Of Temperature On The Overall Rate Constant Obeyed Arrehenius Equation where The Calculated Activation Energy Was Found To Be 3.096 Kcal/ Mol.
Thesis Includes (87) Figures, (91) Tables , (116) References And Ends With A Summary In Arabic.