الفهرس 
General IntroductionOnly 14 pages are availabe for public view
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Abstract
The present thesis focused on the quantitation of some selected multi-component pharmaceutical dosage forms. These combinations contain two or more active pharmaceutical ingredients in the same dosage form. Methods used for their determination were either UV spectrophotometric methods aided with mathematical manipulations or synchronous fluorescence spectrofluorimetric or RP-HPLC methods. The developed methods were optimized and validated. The thesis is composed of four parts: Part I: General introduction This part presents a general introduction about fixed dose combination dosage forms, their advantages, and different analytical techniques which are used for the simultaneous determination of their components. It also describes how to assess method greenness using the analytical Eco-scale and how to evaluate method greenness using ”green analytical procedure index ”GAPI tool. Part II: Simultaneous determination of amlodipine besylate and celecoxib in their fixed dose combination tablets This part consists of four chapters: Chapter 1: Introduction and Literature Review of Amlodipine besylate and Celecoxib This chapter includes an introduction about the chemical, physicochemical properties and mechanism of action of amlodipine besylate and celecoxib and presents a review of literature about the analytical methods recently reported for their assay. 2: Fast and green RP-HPLC method with dual detection using UV and fluorescence detectors for simultaneous determination of amlodipine besylate and celecoxib in fixed-dose combination tablets. In this chapter, green dual detection simple and sensitive RP-HPLC approaches were developed and validated for estimation of amlodipine besylate and celecoxib simultaneously in their binary mixtures. Separation was achieved by using Thermo™ ODS Hypersil reversed phase column with a mobile phase composed: acetonitrile: 50 mM phosphate buffer, pH 5.5 (60:40, v/v) as mobile phase eluted at a rate of 1 mL/min at 40 oC, using both fluorescence detector and variable wavelength UV detector. The fluorescence detector was adjusted at 360/ 446 nm (ex/em) for the first 5 minutes to determine amlodipine besylate, and then switched online to 265/359 nm (ex/em) for determination of celecoxib. The VWD at a wavelength =240 nm. Calibration curves were linear across concentration ranges of 0.05–2 μg.mL-1 and 0.05–10 μg.mL-1 using fluorescence detector and across concentration ranges of 0.5–35 μg.mL-1 and 5-50 μg.mL-1 is obtained using UV detector for amlodipine besylate and celecoxib, respectively. The method was successfully applied for estimation of both drugs in laboratory prepared mixture containing all potential excipients present in tablets dosage form. Evaluation of greenness of the approaches was also performed and the developed approaches were found to have an analytical Eco-Scale value of 87 indicating HPLC methods greenness is excellent. This method was published in Journal of Separation Science, 43 (16), 3197–3205, 2020. 3: Green simultaneous determination of amlodipine besylate and celecoxib by dual wavelength and simultaneous equation spectrophotometric methods. This chapter presents the development and validation of two spectrophotometric methods; dual wavelength (I) and simultaneous equation (II) methods. Both methods were used for estimation of amlodipine besylate and celecoxib simultaneously in binary mixture and laboratory-prepared mixtures that comprise potential excipients contained in the dosage form of tablets. Method I was based on recording the zero order spectra of mixtures and then measuring the absorbance directly at 357 nm for determination of amlodipine besylate and measuring the absorbance difference (A) between 252 nm and 357 nm for determination of celecoxib. While method II was based on generating two simultaneous equations at 357 nm and 252 nm and solving them. Linearity range for amlodipine besylate using methods I and II was found to be 5- 65 μg. mL-1. For celecoxib the linearity range was found to be 1- 25 μg. mL-1 for both methods. The suggested methods were effectively used to determine the presence of celecoxib and amlodipine besylate in a laboratory-prepared mixture that contained every potential excipient that may be found in a dosage form. Mean percentage recoveries ± SD were found to be 101.157± 0.750 and 101.765± 0.140 for method I and 101.603± 0.750 and 100.549± 1.262 for method II for amlodipine besylate and celecoxib, respectively. This method was published in Journal of Advanced Medical and Pharmaceutical Research, 2(1), 16-23, 2021. 4: Ecofriendly synchronous fluorescence spectrofluorimetric method for quantitation of amlodipine besylate and celecoxib in their fixed-dose combination tablets. This chapter presents the development and validation of a synchronous fluorescence spectrofluorimetric approach for estimation of amlodipine besylate and celecoxib simultaneously. This approach was based on recording of the synchronous fluorescence spectra of their mixtures in methanol by simultaneous scanning of the excitation and emission monochromators at Δλ of 90 nm. Then the synchronous fluorescence spectra intensities were measured at 447 nm for determination of amlodipine besylate and 350 nm for determination of celecoxib. A blank experiment was performed simultaneously. Calibration curves were linear over the concentration range 0.05-3.6 μg. mL-1 for amlodipine besylate and in the range 0.1-1.4 μg. mL-1 for celecoxib. Mean percentage recoveries ± SD were found to be 101.147 ± 0.545 and 99.669 ± 1.418 for estimation of amlodipine besylate and celecoxib, respectively in their mixtures. The approach was effectively used to identify both medications in a laboratory-prepared mixture that included all potential excipients present in tablet dosage form. Part III: Simultaneous determination of montelukast sodium and fexofenadine hydrochloride in their newly released fixed dose combination. This part is also composed of three chapters; Chapter 1: Introduction and Literature Review of montelukast sodium and fexofenadine hydrochloride This chapter includes an introduction about the chemical, physicochemical properties and mechanism of action of montelukast sodium and fexofenadine hydrochloride and presents a review of literature about the analytical methods recently reported for their assay. Chapter 2: Facil and green spectrophotometric methods for simultaneous determination of montelukast sodium and fexofenadine hydrochloride in their fixed dose combination via simultaneous equation and dual wavelength approaches. This chapter presents the development and validation of two spectrophotometric methods; dual wavelength (I) and simultaneous equation (II). Both methods were used for estimation of montelukast sodium and fexofenadine hydrochloride simultaneously in binary mixtures and laboratory-prepared mixtures that comprise potential excipients contained in the dosage form of tablets. Method I was based on recording the zero order spectra of mixtures and then measuring the absorbance directly at 345 nm for determination of montelukast sodium and measuring the absorbance difference (A) between 260.4 nm and 365.8 nm for estimation of fexofenadine hydrochloride. While method II was based on generating two simultaneous equations at 345 nm and 260.4 nm and solving them. Linearity range for montelukast sodium using methods I and II was found to be 0.5-20 μg.mL-1. For fexofenadine hydrochloride the linearity range was found to be 10-200 μg.mL-1 for both methods. The developed methods were successfully applied for the determination of montelukast sodium and fexofenadine hydrochloride in a laboratory-prepared mixture that contained every potential excipient that may be found in a dosage form. Mean percentage recoveries ± SD were found to be 100.998± 0.883 and 100.159± 1.038 for method I and 100.477± 1.542 and 99.782± 1.739 for method II for montelukast sodium and fexofenadine hydrochloride, respectively. 3: Green synchronous fluorescence spectroscopic approach for simultaneous quantitation of montelukast sodium and fexofenadine hydrochloride in combined pharmaceutical formulation. This chapter presents the development and validation of a synchronous fluorescence spectrofluorimetric approach for estimation of montelukast sodium and fexofenadine hydrochloride simultaneously. This method was based on recording of the synchronous fluorescence spectra of their mixtures in methanol by simultaneous scanning of the excitation and emission monochromators at Δλ of 60 nm. Then the synchronous fluorescence spectra intensities were measured at 405 nm for determination of montelukast sodium and 288 nm for determination of fexofenadine hydrochloride. A blank experiment was performed simultaneously. Calibration curves were linear over the concentration range 0.1-2 μg. mL-1 for montelukast sodium and in the range 2-20 μg. mL-1 for fexofenadine hydrochloride. Mean percentage recoveries ± SD were found to be 100.569±1.111 and 100.179±0.544 for estimation of montelukast sodium and fexofenadine hydrochloride, respectively in their mixtures. The approach was effectively used to identify both medications in a laboratory-prepared mixture that included all potential excipients present in tablet dosage form. Part IV: Quantitative analysis of newly approved antidiabetic ternary combination. This part consists of two chapters: Chapter 1: Introduction and Literature Review of dapagliflozin, saxagliptin hydrochloride, and metformin hydrochloride This chapter includes an introduction about the chemical, physicochemical properties and mechanism of action of dapagliflozin, saxagliptin hydrochloride, and metformin hydrochloride and presents a review of literature about the analytical methods recently reported for their assay. Chapter 2: Development and validation of a green dual detection RP-HPLC method for simultaneous determination of dapagliflozin, saxagliptin hydrochloride, and metformin hydrochloride: Application to laboratory prepared combination tablets and human plasma. In this chapter, green, dual detection, simple and sensitive RP-HPLC approaches was developed and validated for estimation of dapagliflozin, saxagliptin hydrochloride, and metformin hydrochloride simultaneously in their ternary mixtures. Separation was achieved by using Thermo™ ODS Hypersil reversed phase column with a mobile phase composed methanol: 50 mM phosphate buffer, pH 5.5 with 1% TEA eluted according to gradient elution schedule at a rate of 1.5 mL/min at 25 oC, using both fluorescence detector and variable wavelength UV detector. The fluorescence detector was adjusted at 223/ 302 nm (ex/em) for determination of dapagliflozin. The UV detector was programmed at a wavelength =218 nm. Calibration curves were linear across a concentration ranges of 2.5-80 μg.mL-1 for dapagliflozin using fluorescence detector and over the ranges of 5-100 μg.mL-1, 5-100 μg.mL-1 and 50- 1000 μg.mL-1 using UV detector for dapagliflozin, saxagliptin hydrochloride and metformin hydrochloride, respectively The approaches were effectively used to identify three medications in a laboratory-prepared mixture that included all potential excipients present in tablet dosage form. • Application to spiked human plasma: The approaches were applied for estimation of dapagliflozin, saxagliptin hydrochloride and metformin hydrochloride in spiked human plasma, the maximum recovery was obtained by protein precipitation employing methanol. The method was optimized and validated, the mean % recovery ± SD was found to be 101.229 ± 0.577 for dapagliflozin using fluorescence detector and100.742 ±0.503 for dapagliflozin, 100.365 ± 0.870 for saxagliptin hydrochloride, and 99.526 ±0.753 for metformin hydrochloride using UV detector. As a result, it is recommended to use these methods in pharmacokinetics studies. For all previously mentioned methods described in the previous parts, the statistical analysis of the results including the derivation of the regression equations for the different calibration curves, accuracy, precision, detection and quantitation limits and specificity have been carried out.