الفهرس 
DETERMINATION OF TOLFENAMIC ACID AND TWOOnly 14 pages are availabe for public view
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Abstract
This thesis consists of four parts in addition to references , arabic and english summaries. Each part includes an introduction, literature review, descriptive experimental work for the studied drugs, results, discussion and ends with a conclusion.
Part I: DETERMINATION OF TOLFENAMIC ACID AND TWO POTENTIAL IMPURITIES
This part includes five sections.
Section (A): Introduction and Literature Review
This section includes an introduction about Tolfenamic Acid (TOL) and two potential impurities 2-Chlorobenzoic acid (CBA) and 3-chloro-2-methylaniline (CMA) and summary of the published methods developed for TOL analysis in its mixtures with Anthranilic acid derivatives formulation .
Section (B): Determination of Tolfenamic Acid and Two Potential Impurities by Different Spectrophotometric Methods
In this section, zero order absorption spectra, dual wavelength and the recently developed dual wavelength manipulating ratio spectra methods have been applied for determination of TOL,CMA and CBA in their mixture , respectively, using 0.1N HCl as a solvent. TOL concentrations were determined by measuring the absorbance at its λ max (285.4 nm). While the absorbance difference between 214.6 nm and 224.6 nm was used for determination of CMA (at which zero difference for TOL and CBA was observed). Finally concentrations of CBA were calculated by dual wavelength manipulating ratio spectra. where ratio difference between 232.6 nm and 255.6 nm was used (at which zero difference for TOL and CMA was observed) for measuring CBA concentration.
Section (C) : Simultaneous Determination of Tolfenamic Acid (TOL) and Two Potential Impurities by Multivariate Calibration Methods
Multivariate calibration models, such as PLS and PCR has been successfully applied as selective stability indicating methods for determination of the ternary mixture of TOL, CBA and CMA.
To validate the predictive ability of the developed models, they were applied to predict the concentrations of TOL, CBA and CMA in an external validation set. Statistical analysis with the reported method showed no significant difference.
Section (D): Simultaneous Determination of Tolfenamic Acid (TOL) and Two Potential Impurities by TLC- Densitometric Method
This section is concerned with the development of sensitive, economic and specific stability indicating TLC-Densitometric method for determination of TOL, CBA and CMA in their bulk powder and pharmaceutical formulations. The three proposed components were well separated using hexane: chloroform: acetone: acetic acid (75: 25: 20: 0.1, by volume) as a developing system and the separated bands were scanned at 240 nm. The developed TLC-Densitometric method was applicable for determination of TOL in its tablets where good results were observed indicating no interference from excipients.
Section (E): Simultaneous Determination of Tolfenamic Acid (TOL) and Two Potential Impurities by RP-HPLC Method
In this section, a precise, accurate and selective RP-HPLC with isocratic elution has been investigated and validated for quantitative analysis of TOL, CBA and CMA. The chromatographic separation was achieved by using 0.05 M KH2PO4 buffer (pH= 3): acetonitrile (45: 55, v/v) as mobile phase, the separation was performed on C18 column maintaining the flow rate at 1mL min-1 and scanning the eluted components at 230 nm. The suggested method has been applied for determination of the proposed drug in different laboratory prepared mixtures and in pharmaceutical formulation.
Part II: DETERMINATION OF AMLODPINE BESYLATE AND PERINDOPRIL ARGININE
This part includes five sections.
Section (A): Introduction and Literature Review
This section includes an introduction about the pharmacological action of Amlodipine Besylate (AB) and Perindopril Arginine (PA), their chemical structure, physical properties and summary of the methods developed for their analysis in their formulations and in their binary mixture.
Section (B): Determination of Amlodipine Besylate and Perindopril Arginine by Different Spectrophotometric Methods
In this section, different spectrophotometric methods have been applied for determination of AB and PA in their binary mixture using 0.1N NaOH as a solvent. AB concentrations were determined by measuring the absorbance at its λ max (364.6 nm). The absorbance difference between 215.6nm and 226.6 nm were used for determination of PA by dual wavelength method; Moreover Ratio subtraction method was also used for determination of PA by measuring its absorbance at its λ max (217.2 nm).
The developed methods were applied for determination of the studied drugs in different laboratory prepared mixtures. No significant difference was found between the proposed methods and the reported one when they were compared using student’s t-test and F-test.
Section C: Determination of Amlodipine Besylate and Perindopril Arginine by Mean Centering of Ratio Spectra Spectrophotometric Method
In this method, the mean centered ratio spectra amplitudes at 360-361 nm (peak to peak) for quantitation of AB and 312-313 nm (peak to peak) for quantitation of PA and nm were used for quantitation of both AB and PA. The suggested method has been applied for determination of AB and PA in their pure form and in their pharmaceutical preparations. Statistical comparison with the reported RP-HPLC Method showed no significant difference.
Section D: Simultaneous Determination of Amlodipine Besylate and Perindopril Arginine by RP-HPLC Method
In this section, an accurate and selective RP-HPLC method has been investigated and validated for quantitative analysis of AB and PA in their binary mixture. In this method, an isocratic elution was performed at ambient temperature on C18 column with a mobile phase consisting of phosphate buffer: acetonitrile [(60:40, v/v) pH=4.6] at flow rate of 1 mL min-1 and the detection was performed at 210nm.
Statistical comparison of the results obtained by the proposed method and the reported one showed no significant difference regarding both accuracy and precision.
Part III: DETERMINATION OF AMLODPINE BESYLATE AND ATORVASTATIN CALCIUM
This part includes five sections.
Section (A): Introduction and Literature Review
This section includes an introduction about the pharmacological action of Amlodipine Besylate (AB) and Atorvastatin Calcium (ATR), their chemical structure, physical properties and summary of the methods reported for their analysis either together or with other components.
Section B: Simultaneous Determination of Amlodipine Besylate and Atorvastatin Calcium by Isoabsorptive Spectrophotometric Method
In this section, isoabsorptive spectrophotometric (ISO) method has been applied for determination of AB and ATR in their binary mixture using methanol as a solvent. The absorbance value at the isoabsorptive point (λ 232 nm) was used for calculating the total mixture concentration, on the other hand AB degradation product concentration could be selectively determined using the absorbance value at 359.6 nm, and by subtraction ATR content in the mixture could be determined.
The developed methods have been applied for determination of the studied components in different laboratory prepared mixtures; also they were applied for dosage form. The results obtained by applying the proposed methods for determination of AB and ATR were statistically compared to those obtained by applying the reported RP-HPLC and no significant difference were found regarding both accuracy and precision.
Section (C): Simultaneous Determination of Amlodipine Besylate and Atorvastatin Calcium by Dual Wavelength Spectrophotometric Method
In this section, Dual wavelength method has been applied for determination of AB and ATR in their binary mixture using methanol as a solvent. AB concentrations were determined by measuring the absorbance difference at 219nm and 230 nm. While ATR concentrations were determined by measuring the absorbance difference at 225.8 nm and 244.8 nm. The results obtained by applying the proposed method for determination of pure AB and ATR in their dosage form were statistically compared to those obtained by a reported RP-HPLC method and no significance difference was found regarding both accuracy and precision.
Section (D): Simultaneous Determination of Amlodipine Besylate, Perindopril Arginine and Atorvastatin Calcium by HPTLC-Densitometric Method
The developed HPTLC-Densitometric method depended on chromatographic separation of AB, PA and ATR using chloroform: methanol: deionized water: glacial acetic acid: triethylamine (100:70:2:1:4, by volume) as developing system. The separated bands were scanned at 210 nm in the range of 0.2-10 μg band-1 for both AB and PA and in the range of 1-10 μg band-1 for ATR. The Proposed HPTLC-Densitometric method was applied successfully for determination of AB /PA and AB/ATR in their pharmaceutical formulations.
Section (E): Simultaneous Determination of Amlodipine Besylate in combination with Perindopril arginine or Atorvastatin calcium by Multivariate Calibration Methods with Application of Model Updating
Multivariate calibration models, such as PLS and PCR have been successfully applied for determination of AB and PA, the developed PLS and PCR models were updated for determination of AB and ATR in their combined dosage forms.
To validate the predictive ability of the developed models, they were applied to predict the concentrations of AB and PA in an external validation set. Statistical analysis of the results obtained by the developed models was compared with those of the reported RP-HPLC methods. No significant difference was found, within probability of 95 % regarding both accuracy and precision.
Part IV: Appendix
This part includes a brief idea about the instruments, solvents and chemicals used throughout the whole work. In addition to the detailed preparation of the solutions used in each part.
This thesis refers to 157 references, contains 66 tables, 55 figures and ends with an Arabic summary.