الفهرس 
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Abstract
The present thesis involves the determination of some selected antidiabetics and some cardiovascular drugs. The developed methods were either spectrophotometric methods or RP-HPLC methods. The developed methods were optimized and validated. Part I: General introduction This part represents a general introduction about diabetes mellitus, cardiovascular diseases and their medications. Part II: Literature review This chapter represents an introduction about the chemical and physicochemical properties of some antidiabetic drugs: metformin (MET), empagliflozin (EMP), linagliptin (LIN), pioglitazone (PIO) and glimepiride (GLM), alogliptin (ALG) and two antihypertensive drugs: nebivolol (NEB) hydrochloride and valsartan (VAL). Also, it includes a review of literature about the analytical approaches reported for quantitation of these drugs in their single and combined dosage forms. Part III: Development and validation of new RP-HPLC analytical methods for simultaneous determination of some antidiabetic drugs and antihypertensive drugs. This part consists of three chapters: Chapter 1: Analytical Quality by Design Based on Design Space in RP-HPLC Analysis for Simultaneous Estimation of Metformin, Linagliptin and Empagliflozin This chapter includes an introduction about employing the quality by design (QbD) paradigm and its advantages. This chapter presents simultaneous determination of metformin (MET), empagliflozin (EMP) and linagliptin (LIN) in their ternary mixtures using quality by design. The developed technique was successfully applied for the simultaneous estimation of metformin (MET), empagliflozin (EMP) and linagliptin (LIN) in their in a laboratory prepared tablet containing all possible excipients present in tablet dosage form and in spiked human plasma samples. Quality risk management principles were applied for determining the critical method parameters (CMPs) affecting the simultaneous determination of metformin hydrochloride (MET), linagliptin (LIN), and empagliflozin (EMP) by RP-HPLC. The ternary mixture was successfully resolved in 5 min with linearity range of (0.1-600) μg/mL for MET and (0.05-50) μg/mL for LIN and EMP. This chapter was published in Royal Society Open Science, 2022. 9(6): p. 220215. Chapter 2: Deduction of the Operable Design Space of RP-HPLC Method for the Simultaneous Estimation of Metformin, Pioglitazone, and Glimepiride It presents the development and validation of quality by design RP-HPLC for the simultaneous quantitation of metformin (MET), pioglitazone (PIO) and glimepiride (GLM) in their ternary mixtures. The developed quality by design method was successfully applied for the simultaneous determination of metformin (MET), pioglitazone (PIO) and glimepiride (GLM) in a laboratory prepared tablet containing all possible excipients present in tablet dosage form and in spiked human plasma. AQbD approach depended on the studding of quality target product profile (QTPP), analytical target profile (ATP) and risk assessment tool for factors or critical method parameters (CMPs) that affect the method performance. Regarding to International Conference on Harmonization (ICH)Q8(R2), ICH Q9 guidelines, the (ATP) it was used for establishment of the method operable design region (MODR). * This chapter was published in Scientific reports, 2023. 13(1):pages (1-13). Chapter 3: Green HPLC-Fluorescence Detection Method for Simultaneous Estimation of Nebivolol and Valsartan in Their Combined Dosage Form: Application to Spiked Human Plasma This chapter presents an introduction about validation of bioanalytical methods and their importance. It also presents the development and validation of bioanalytical technique for simultaneous estimation of nebivolol (NEB) and valsartan (VAL) in their binary mixtures, laboratory prepared tablets containing all possible excipients present in tablet dosage form and in spiked human plasma samples. The validation of the developed approach was in accord to ICH guidelines Q2 (R1) for estimation of NEB and VAL in their tablets and validated according to USFD and EMEA bio-analytical validation guidelines for quantitation of NEB and VAL in spiked human plasma. The greenness of the proposed approach was estimated according to the analytical Eco-Scale approach. Part IV: Univariate and multivariate spectrophotometric methods for simultaneous determination of some antidiabetics. This part consists of four chapters: Chapter 1: Using Eosin Y as a Facile Fluorescence Probe in Aloglipitin Estimation: Application to Tablet Dosage Forms and Content Uniformity Testing This chapter presents the development and validation of spectrofluorimetric technique for the estimation of alogliptin (ALG) using eosin y in its pure and tablet dosage forms. The developed methods were successfully applied for the determination of alogliptin (ALG) in its tablet dosage form and also applied for the content uniformity testing. The developed method application was successfully extended for ALG content uniformity test (CU). The distribution fraction (DF), rate constants (K), and free energy changes (ΔG°) were calculated. This chapter was published in Spectrochemica Acta Part A: Molecular Biomolecular Spectroscopy, 2023. 285: p. 121919. Chapter 2: Four Validated Spectrophotometric Approaches for Simultaneous Estimation of Linagliptin and Empagliflozin in Their Pure and Tablet Forms This chapter includes an introduction about four spectrophotometric methods including area under curve (AUC), first derivative of ratio spectrophotometric (1DD) method, ratio difference method (RD) and dual wavelength method (DWL) as well as their advantages. It also presents the development and validation of these four univariate spectrophotometric approaches for simultaneous determination of linagliptin (LIN) and empagliflozin (EMP) in their binary mixtures. The developed methods were successfully applied for the estimation of linagliptin (LIN) and empagliflozin (EMP) in a laboratory prepared tablet containing all possible excipients present in tablet dosage form. Chapter 3: Three Validated Spectrophotometric Approaches for Simultaneous Estimation of Pioglitazone and Linagliptin in Pure Forms and Tablet Form This chapter includes an introduction about three spectrophotometric methods including first derivative of ratio spectrophotometric (1DD) method, ratio difference method (RD) and simultaneous equation method (S.E) as well as their advantages. It also includes the development and validation of these three univariate spectrophotometric techniques for simultaneous estimation of linagliptin (LIN) and pioglitazone (PIO) in their binary mixtures. The developed approaches were successfully applied for the estimation of linagliptin (LIN) and pioglitazone (PIO) in a laboratory prepared tablet containing all possible excipients present in tablet dosage form. Chapter 4: Introducing Gradient Boosting Regression Model for Multivariate Quantitation of Pioglitazone, Alogliptin and Glimepiride in Pure Forms and Tablets with Aid of UV- Spectrometry: A Comparative Study This chapter includes a comparison between the performance of four multivariate models partial least square (PLS), artificial neural networks (ANN), support vector regression (SVR) and extreme gradient boosting (XG Boost) algorithm for the determination of the unique anti-diabetic mixture of pioglitazone (PIO), alogliptin (ALG) and glimepiride (GLM) in pharmaceutical formulations with aid of UV- spectrometry. GLM, the component completely overlapped with (PIO) and (ALG) spectra with narrow spectral range and low absorption characteristics. It was only successfully determined using extreme gradient boosting (XG Boost) algorithm with root mean squared error of prediction (RMSEP) for the proposed model of 5.86*10-4. The results showed that (XG Boost) algorithm had best performance regarding the determination of the three components in proposed mixtures with lowest (RMSEP) and standard deviation.