الفهرس 
Introduction and Literature reviewOnly 14 pages are availabe for public view
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Abstract
This thesis is concerned with the analysis of certain drugs used in treatment of conjunctivitis namely; Prednisolone acetate, Sulfacetamide sodium and Tobramycin sulphate.
The thesis includes six parts:
PART (I): Introduction and Literature review
It includes a brief idea about conjunctivitis, drugs used for its treatment, review of their structures, their chemical and physical properties and different analytical methods reported in literature applied for the determination of the studied drugs in pure form, pharmaceutical formulations and biological samples.
PART (II): Spectrophotometric Methods for Determination of Certain Drugs used in Treatment of Conjunctivitis
Section (A): Spectrophotometric Methods for Simultaneous Determination of Prednisolone acetate and Sulfacetamide sodium in Bulk Powder and in their Combined Dosage Form.
Four validated eco-friendly spectrophotometric methods were described for the simultaneous quantification of Prednisolone acetate and Sulfacetamide Sodium in their pure form and their pharmaceutical formulation.
Two smart spectrophotometric methods using unified regression equation namely Response Correlation and Amplitude Modulation and two other ratio spectra manipulating methods namely; Ratio subtraction and Ratio difference coupled with constant multiplication were developed and validated for the simultaneous analysis of a binary mixture of the mentioned two drugs. The proposed methods were validated according to ICH guidelines and were found to be within the acceptable ranges.
The proposed methods were successfully applied for determination of both drugs in their combined dosage form; Blephamide ophthalmic suspension® with high accuracy and selectivity, and the validation of the proposed methods was further assessed by applying standard addition technique. The proposed methods were statistically compared with the validated reported methods in literature and no statistically significant difference was found.
Section (B): Efficient Absorbance Quenching of PVP-capped Silver Nanoparticles for Determination of Tobramycin sulphate in its Pharmaceutical Dosage Form and Spiked Human Plasma.
A fast eco-friendly spectrophotometric method is developed for determination of a non-UV absorbing drug, Tobramycin sulphate, in its bulk powder, pharmaceutical dosage form and spiked human plasma using PVP-capped silver nanoparticles as a colorimetric probe. This method is based on measuring the decrease in the absorbance spectrum of silver nanoparticles at 415.0 nm by increasing the concentration of Tobramycin sulphate. The absorbance quenching is probably due to the formation of hydrogen bonds between the PVP-capped silver nanoparticle and the drug, resulting in an aggregation which leads to color change and could be measured quantitatively. Different factors affecting the spectrophotometric determination of Tobramycin sulphate as; the effect of silver nanoparticle concentration, pH, buffer type and reaction time were studied and optimized using full factorial design, in which the predicted model fits well to the experimental data as proved by ANOVA results. Validation of the proposed method was performed according to ICH guidelines and was found to be within the acceptable ranges. The proposed method was successfully applied for determination of Tobramycin sulphate in its pharmaceutical dosage form; Tobrin ophthalmic solution®, Tobrin ophthalmic ointment® and spiked human plasma with high accuracy and selectivity, and the validation of the proposed method was further assessed by applying standard addition technique. The proposed method was statistically compared with the validated reported method in literature and no statistically significant difference was found.
PART (III): Electrochemical Methods for Determination of Certain Drugs used in Treatment of Conjunctivitis
Section(A): Potentiometric Method for Determination of Tobramycin sulfate using Bare, Carbon nanodots and Silver Nanoparticles Modified Carbon Paste Electrodes in its Pharmaceutical Dosage Form and Spiked Human Plasma.
In this section, two novel carbon paste electrodes modified with carbon nanodots (C-dots) and silver nanoparticles (AgNPs) were fabricated, for the first time, for potentiometric determination of Tobramycin sulphate, which was recently employed in the treatment protocol of COVID-19. The two modified electrodes were compared to a bare carbon paste one, to study the advantages of addition of nanoparticles in potentiometric sensors which was found to improve the performance characteristics of the electrode in terms of sensitivity and selectivity and also prolonged its lifetime.
Two inexpensive and simple methods for synthesis of carbon nanodots were developed and compared to each other, namely hydrothermal and microwave-assisted methods. The synthesized carbon nanodots were characterized using transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis), photoluminescence (PL), Fourier transform-infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The synthesized microwave carbon nanodots had smaller particle size, thus were used for the modification process. The electrochemical performance of the proposed sensors was evaluated according to the IUPAC recommendation data and was found to be within the acceptable ranges. This developed potentiometric method was used for quantification of Tobramycin in its co-formulated dosage form; Lotepred® T ophthalmic solution and spiked human plasma with good recovery results and without interference of the co-formulated drug Loteprednol etabonate and excipients. The proposed method was statistically compared with the validated reported method in literature and no statistically significant difference was found.
Section (B): Determination of Sulfacetamide sodium by Cobalt Based Nanoparticles Coated Graphite Sensors in Dosage Form and Aqueous Humor.
This section proposes two sensors for the potentiometric determination of Sulfacetamide sodium. Sensor 1 is a bare coated graphite electrode plasticized with DOP and Tetrakis-decyl ammonium bromide as a sensing element.
Sensor 2 is a Cobalt oxide nanoparticles modified coated graphite electrode. The latter electrode showed several advantages over the bare one in terms of Nernstian slope, sensitivity, selectivity and life time. The electrochemical performance of the proposed sensors was evaluated according to the IUPAC recommendation data and was found to be within the acceptable ranges. Both electrodes were used for analysis of Sulfacetamide sodium in pure solutions, pharmaceutical dosage form and spiked rabbit aqueous humor with good recovery percentages without the interference of the co-formulated drug Prednisolone acetate and excipients. The proposed method was statistically compared with the validated reported method in literature and no statistically significant difference was found.
PART (IV): chromatographic Methods for Determination of Certain Drugs used in Treatment of Conjunctivitis
Section (A):TLC-densitometric Method for Simultaneous Determination of Prednisolone acetate and Sulfacetamide sodium in their Combined Dosage form followed by their Finger Prints Evaluation using Online HPTLC–ESI-MS.
This section was focused on the development of an eco-friendly, simple, rapid and accurate TLC-densitometric method for simultaneous determination of Prednisolone acetate and Sulfacetamide sodium in their pharmaceutical dosage form which can be used for their routine analysis in quality control labs. This method offered superiority in terms of environmental friendliness, simplicity, speed, and cost, as it did not require sophisticated or expensive instruments. This method was performed on silica plates F254 using a mobile phase composed of methanol and ethyl acetate in a ratio (90:10 v/v) and spots were detected under UV at 254.0 nm. Another advantage of the proposed method is the finger prints evaluation of the mentioned drugs using online HPTLC-ESI-MS. Validation of the proposed method was performed according to ICH guidelines and was found to be within the acceptable ranges. The proposed method were successfully applied for determination of both drugs in their combined dosage form; Blephamide ophthalmic suspension® with high accuracy and selectivity, and the validation of the proposed method was further assessed by applying standard addition technique. The proposed method was statistically compared with the validated reported method in literature and no statistically significant difference was found.
Section (B):HPLC-PDA Method for Simultaneous Determination of Prednisolone acetate and Sulfacetamide sodium in Bulk, Pharmaceutical Dosage Form and Spiked Rabbit Aqueous Humor.
This section was focused on the development of an eco-friendly simple, rapid and accurate HPLC-PDA method for simultaneous determination of Prednisolone acetate and Sulfacetamide in bulk, pharmaceutical dosage form and spiked rabbit aqueous humor. This method offered superiority in terms of environmental friendliness, short run time, simplicity, as it did not require sophisticated or expensive sample extraction technique.
The separation was performed using Kromasil C18 (150 mm x 4.6 mm, 5µm) as a stationary phase, (methanol: water) in a ratio (60:40 v/v) adjusted to pH 5.0. by orthophosphoric acid and with the addition of 1 mL Tri-ethyl amine as an anti-tailing agent as the mobile phase, flow rate : 1 mL/min , injection volume :10 µL and the detection was done at 254.0 nm. Validation of the proposed method was performed according to ICH guidelines and was found to be within the acceptable ranges. The proposed method was successfully applied for determination of both drugs in their combined dosage form; Blephamide ophthalmic suspension® with high accuracy and selectivity, and the validation of the proposed method was further assessed by applying standard addition technique. The proposed method was statistically compared with the validated reported method in literature and no statistically significant difference was found. Owing to the simplicity and successfulness of the proposed method in determining the proposed drugs in spiked rabbit aqueous humor, it could be applied in quality control laboratories, bioequivalence and bioavailability centers.
PART (V): Greenness Assessment
The greenness of our spectrophotometric, potentiometric and chromatographic methods was evaluated using the most recent greenness assessment tool Green Analytical Procedure Index (GAPI).
PART (VI): General Discussion
It includes comparison between the different proposed methods and the several advantages offered by these methods.
References
The thesis includes 61 tables, 58 figures and 313 references and ends with an Arabic summary.
Key words: Prednisolone acetate, Sulfacetamide sodium, Tobramycin sulphate, carbon paste electrode, coated graphite electrode, quality by design.