الفهرس 
Part I: Introduction and Analytical ReviewOnly 14 pages are availabe for public view
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Abstract
The presented thesis is concerned with the densitometric and spectroscopic methods for determination of mainly two oral hypoglycemic drugs (Dapagliflozin, Empagliflozin) in the presence of their combinations.
It consists of three main parts and six chapters:
Part I: Introduction and analytical review
This section includes a general introduction on types of diabetes mellitus, its classification, its prevalence, and provides classifications of anti-diabetic drugs, then concentrates on the physical and pharmacological properties of dapagliflozin (DAPA), empagliflozin (EMPA) which belong to synthetic type of oral hypoglycemic drugs called Gliflozins. This part also includes a summary of literature review concerning the reported analytical methods for the determination of the cited drugs.
Part II: Densitometric methods
This part consists of four chapters:
Chapter 1: TLC-spectrodensitometric method for simultaneous determination of dapagliflozin and rosuvastatin in rabbit plasma: Stability indicating assay and kinetic studies, this chapter has been published in RSC Advances ,2020, Volume 10, pages 40795-40805
TLC spectrodensitometric method was developed using ethyl acetate: methanol (5:0.1 v/v/) as mobile phase for simultaneous separation and determination of DAPA and ROSV in bulk, dosage forms and rabbit plasma for the first time. The method offers high selectivity and sensitivity with acceptable reproducibility. Regression plots revealed linear relationships in the concentration range 20-2500 ng/band and 10-2500 ng/band with LODs of 6.60 and 3.57 ng/band for both DAPA and ROSV, respectively. The forced degradation was carried out according to ICH guidelines which indicate that DAPA and ROSV undergo degradation to a different extent under UV light.
Chapter 2: Simple TLC-spectrodensitometric method for studying lipophilicity and quantitative analysis of hypoglycemic drugs in their binary mixture. Was published in Biomedical chromatography 1/5/2021.
In this chapter, simple, sensitive, and selective TLC-spectrodensitometric method was proposed for the simultaneous separation and determination of DAPA and MET in their binary mixture. The determination was performed on silica gel and mobile phase consisting of 0.5M (NH4)2SO4: methanol (3:7 v/v), and UV detection at λ = 237 nm. The method was validated according to ICH guidelines. The linearity of the proposed method was found in the range of 45 – 1000 and 50 – 1500 ng/band with LODs of 15 and 13 ng/band) for DAPA and MET, respectively. The TLC method was used to determine DAPA and MET in pharmaceutical tablets and spiked human plasma. The proposed method was used to study the lipophilicity parameters of the two drugs via retention data.
Chapter 3: Innovative TLC-densitometric method with fluorescent detection for simultaneous determination of ternary anti-diabetic mixture in pharmaceutical formulations and human plasma, this chapter was published in Microchemical journal, Volume 165, 5/6/2021, page 106131.
In this chapter, a direct, specific, and sensitive TLC method coupled with fluorescence detection was developed for separation and determination of the three co-administered drugs: GLIM, EMPA and LING in bulk, pharmaceutical formulations and in real human plasma samples with high precision and accuracy. In this study, the reflectance/fluorescence detection mode was applied providing higher sensitivity and selectivity. Good recovery of the studied drugs from plasma indicated that the method is suitable for determination of the investigated drugs without interference from plasma components. Furthermore, the proposed method does not require further sample pretreatment. Moreover, the proposed method provides several advantages, such as short time of analysis, large sample capacity per run, and minimal use of solvent. In addition, the use of disposable stationary phase allows the use of strong acidic medium which cannot be used in other chromatographic method such as HPLC methods.
Chapter 4: Quantitative structure–retention relationship (QSRR) aided study for simultaneous micellar thin layer chromatographic (MTLC) separation and estimation of empagliflozin, linagliptin, and metformin HCl in their ternary mixture
This chapter represents the first research which revealed the mechanism of micellar TLC (MTLC) using three types of surfactants (anionic, cationic, and nonionic) and relating the practical data with computational analysis of this type of separation. from this study concluded the most effective 2D and 3D descriptors that are logP (o/w), AMI-IP, E-sol, E-vdw, MR and a-don. For cationic and anionic micelles, the most effective factors are ionization potential and a-donor while for nonionic micelles; the most effective factors are E-vdw, E-sol and logP (o/w). The method was also developed for simultaneous separation and estimation of EMPA, LING and MET tertiary mixture in standards, laboratory-made tablets, and spiked rabbit plasma.
Part III: Spectroscopic methods
A simple and non-invasive FTIR method for the quantitative determination of empagliflozin-metformin and empagliflozin-linagliptin in their binary mixtures.
FTIR spectroscopy was applied successfully for the quantification of EMPA, MET, and EMPA, LING binary mixtures for the first time. FTIR method was developed for direct, inexpensive, and fast quantification of drugs in solid state. The study of interference effect of the excipients, the results obviously showed the sensitivity of FTIR spectroscopic method for pharmaceutical analysis without prior sample preparation. it was found that LODs and LOQs of EMPA and MET were in the range of (5.47 - 4.83) µg/mg and in the range of (1.60 – 1.94) µg/ mg, respectively, while LODs and LOQs of EMPA and LING were in the range of (4.88 – 3.14) µg/mg and (1.77 – 1.03) µg/ mg.