الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 281 |  |  |
| | | from | 281 | | |
Abstract
Different methods for the determination of some pharmaceutical drugs produced by Hikma Company which are used in the treatment of seasonal and perennial allergic conjunctivitis, chronic hepatitis C (CHC) in adults, antibacterial in pure and in pharmaceutical dosage forms have been introduced in this thesis.
These drugs include Azelastine hydrochloride, Benzalkonium chloride, Sofosbuvir, Ledipasvir, Cefixime trihydrate and Sodium benzoate.
The thesis consists of the following chapters:
CHAPTER I: INTRODUCTION
It includes:
I. A review about Compounds Under Study.
II. Literature review about the official and reported methods for the determination of the drugs under investigation.
III. Aim and basis of the work on which the proposed methods were chosen.
CHAPTER II: EXPERIMENTAL
This chapter included all material (Active & In Active), chemicals, solvents, apparatus, solution preparation and chromatographic condition, which are used in the analysis of the drugs under study.
CHAPTER III: RESULTS AND DISCUSSION
The chapter was further divided into three parts:
PART A: Quantitative determination of Azelastine hydrochloride and Benzalkonium chloride in binary mixture.
248
English Summary
I. Simultaneous Determination of Azelastine hydrochloride and Benzalkonium chloride by RP-HPLC Method in their Ophthalmic Solution:
A simple, specific, precise, accurate, and stability-indicating RP-HPLC method was developed and validated for the determination of Azelastine hydrochloride (AZH) and benzalkonium chloride (BAC) in eye drops formulations. RP-HPLC method was performed on the Thermo CPS CN column (150 mm X 4.6 mm, 5 μm particle size, using buffer solution of pH 4.5 containing 50 mM potassium dihydrogen phosphate and 5.7 mM hexane sulfonate: acetonitrile (50:50 v/v) as the mobile phase at a flow rate of 1.5 ml/min, UV detection at 212 nm and run time of 7.5 min. This method is validated according to ICH guidelines and USP requirements for new methods, which include accuracy, precision, selectivity, LOD, LOQ, robustness, ruggedness, linearity and range. Linear relationships were obtained in the ranges of 6.25-50 μg/mL and 5.0-50 μg/mL for AZH and BAC, respectively, with significantly different Rt values of 2.254, 3.432 and 3.946 min for AZH and homologs of BAC (C12, C14) with correlation coefficients of 0.9994 and 0.9992, respectively.
II. Determination of Azelastine Hydrochloride and Benzalkonium Chloride in Their Ophthalmic Solution by Different Spectrophotometric Methods:
Three simple, specific, accurate and precise spectrophotometric methods for the determination of a binary mixture of Azelastine hydrochloride (AZH) and Benzalkonium chloride (BAC) in pure and in their Dosage forms. The methods namely; (A) zero order (D0), (B) ratio difference (RD) and (C)ratio subtraction (RS). In method (A), AZH could be directly determined in the zero order at wave length equals to 284 nm in the range (5.0–50 μg/mL) with good correlation coefficient (0.9994), where no interference from BAC is reported. While BAC was determined by 249
English Summary
different methods in the range (2.0–30 μg/mL). In method (B) BAC determination depends on dividing the spectrum of the binary mixture by the standard spectrum of 20μg/mL AZH as a divisor, then BAC is determined using the difference between the two wavelengths 262 & 208 nm, we here BAC has absorbances and AZH is constant, the difference = (ΔP262.0-208.0) with good correlation coefficient (0.9994). Finally, in method (C) BAC can be determined by dividing the spectrum of the binary mixture by the standard spectrum of 10 μg/mL AZH as a dvisor, then a constant, which is determined as the mean value of the absorbances in the plateau region (230–300 nm), is subtracted; after multiplication by the divisor we obtain a zero order (D0) original spectrum of BAC at 208.0 nm with good correlation coefficient (0.9992). Accuracy, recovery and the selectivity of the developed methods were applied on the laboratory prepared mixtures, standard addition technique and pharmaceutical dosage form. The obtained results for the suggested methods were statistically compared with the reported HPLC one using student’s-t and F-ratio tests, showing that the two methods were accurate and precise.
PART B: Quantitative determination of Sofosbuvir and Ledipasvir in their binary mixture.
I. Assay and Dissolution Methods Development and Validation for Simultaneous determination of Sofosbuvir and Ledipasvir by RP-HPLC Method in Tablet dosage forms:
Specific, accurate, simple, selective and stability-indicating RP-HPLC method is developed and validated for simultaneous determination of Sofosbuvir and Ledipasvir in tablet dosage form for assay and dissolution methods. RP-HPLC method was performed on the Eclipse XDB C18 column (250 mm X 4.6 mm, 5 μm particle size, using buffer solution of pH 3.0 containing 0.02 M potassium dihydrogen phosphate and 5.7 mM hexane sulfonate: acetonitrile (50:50 v/v) as the mobile phase at a flow rate 250
English Summary
of 1.5 ml/min, injection volume 10 μL and UV detection at 254 nm. This method is validated according to BP, USP and ICH requirements for new methods, which include accuracy, precision, selectivity, robustness, ruggedness, LOD, LOQ, linearity and range. Linear relationships were obtained in the ranges of 40-500 μg/mL and 30-300 μg/mL with correlation coefficients of 0.9998, 0.9996, 0.9996 and 0.9993 at Rt value of 2.429 min and 4.529 min for Sofosbuvir and Ledipasvir respectively for assay content and dissolution rate. The forced degradation studies as acidity, alkalinity, oxidation, heat, thermal, humidity and photo degradation were performed according to ICH guidelines. The accurate determination of both drugs is very important for Forensic and Criminal Investigations from the point of view of Forensic pharmacy.
II. Novel spectrophotometric methods for determination of Sofosbuvir and Ledipasvir in their Tablet Dosage form:
The aim of this work is to develop and validate three accurate, simple, selective and specific spectrophotometric methods for the determination of Sofosbuvir (SOF) and Ledipasvir (LDV) in pure and in their dosage forms. LDV can be easily determined in the zero order at a wavelength of 333 nm with good correlation coefficient (0.9997), with no interference from SOF. While the latter could be determined in presence of LED by three novel spectrophotometric methods viz., (I) first derivative (1D), (II) ratio difference (RD) and (III) ratio subtraction (RS). In method (I) SOF has λmax at (274 nm) with good correlation coefficient (0.9997). In method (II), laboratory prepared mixtures were divided by the absorption spectrum of standard 10 μg/mL LDV for the determination of SOF and the ratio spectra were recorded at 208 nm and 270 nm for SOF with good correlation coefficient (0.9993). Finally, in the third one (III), ratio subtraction method is established for resolving the overlap between SOF and LDV by dividing the spectrum of the binary mixture by the standard spectrum of 25 μg/mL 251
English Summary
LDV as a divisor and subtract the constant value determined in the plateau region at 290 –375 nm, then multiply by the divisor to obtain zero order (D0) original spectrum of SOF at 261 nm with good correlation coefficient (0.9994). Accuracy, recovery and the selectivity of the developed methods were confirmed by applying the standard addition technique, testing on authentic mixtures and application on pharmaceutical dosage forms. The obtained results from the proposed methods were statistically compared with those obtained from the recently published HPLC method for their simultaneous determination using one-way analysis of variance (ANOVA) where no significant difference was observed between the proposed methods and the well-established ones which prove their validity for the analysis of this binary mixture.
PART C: Quantitative determination of Cefixime trihydrate and Sodium benzoate in their binary mixture.
I. Validation of a Novel and Sensitive RP-HPLC Method for Simultaneous Determination of Cefixime Trihydrate and Sodium Benzoate in Powder for Oral Suspension Dosage Form:
A novel, specific, precise, simple, and accurate RP-HPLC method was developed and validated for simultaneous determination of Cefixime trihydrate (CFX) and Sodium benzoate (SDM) in powder for oral suspension (POS) dosage form. RP-HPLC method was performed on the Agilent Eclipse XDB C8 column (250 mm X 4.6 mm, 5μm particle size, using buffer solution of pH 2.8 containing 0.02M sodium dihydrogen phosphate: Acetonitrile (50:50 v/v) as the mobile phase at a flow rate of 1.0 mL/min, injection volume 10 μL and UV detection at 229 nm. And the total run time was 7.0 min. Linear relationships were obtained in the ranges of 5-200 μg/mL and 2-40 μg/mL for CFX and SDM, respectively, with significantly different Rt values of 2.203 and 3.970 min for CFX and SDM with correlation coefficients (r) >0.9999, limits of detection of 1.36 and 252
English Summary
0.21 μgmL-1 and limits of quantitation was 4.14 and 0.64 μgmL-1 for CFX and SDM, respectively. The obtained results for the suggested method were statistically compared with those obtained by official or the reported method for CFX and SDM, respectively using student’s-t and F-ratio tests, showing that the methods were accurate and precise. This method is validated according to ICH guidelines and USP requirements for new methods, which include accuracy, precision, specificity, LOD, LOQ, robustness, ruggedness, linearity and range. Hence this RP-HPLC method was suitable for quality control of raw materials and finished products. The accurate determination of low levels of both drugs was very important for the analysis of forensic problems.
II. Novel spectrophotometric methods for simultaneous determination of Cefixime trihydrate and Sodium benzoate in powder for oral suspension dosage form:
Up till now, no spectrophotometric methods have been published for determination of Cefixime trihydrate and Sodium benzoate in their pharmaceutical formulation. Novel, specific, precise, simple, and accurate spectrophotometric methods were developed and validated for simultaneous determination of Cefixime trihydrate (CFX) and Sodium benzoate (SDB) in powder for oral suspension (POS) dosage form. Firstly, CFX was directly determined using its extended spectra at 290 nm, where no interference from the co-formulated SDB. In method (I), CFX and SDB were determined by first derivative ratio spectrophotometric method (1DD) at 284 and 318 nm for CFX, while SDB is determined at 216 and 234 nm. In method (II), simultaneous ratio subtraction method (SRSM) was established for resolving the overlap between CFX and SDB by dividing the spectrum of the binary mixture by the standard spectrum of 20 μg/mL CFX as a divisor then subtract the constant value determined in the plateau region at 240–325 nm, then multiply by the divisor to obtain zero order (D0) original spectrum of SDB at 227 nm, further zero order of CFX is 253
English Summary
determined at λmax 290 nm after multiplication the divisor by the obtained constant. Finally, in the third one; ratio difference spectrophotometric method (RDSM), laboratory prepared mixtures were divided by the absorption spectra of standard 40 μg/mL CFX for the determination of SDB and standard 30 μg/mL SDB for the determination of CFX. The ratio spectra were recorded at 231 nm and 290 nm for CFX, while at 223 nm and 250 nm for SDB. The obtained results for the proposed methods were statistically compared with those obtained by the official method for CFX besides the recently published HPLC one for their simultaneous determination using one-way analysis of variance (ANOVA) where no significant difference was observed between the proposed methods and the well-established ones which prove their validity for the analysis of this binary mixture.
CHAPTER IV: SUMMARY AND CONCLUSION
CHAPTER V: REFERENCES
CHAPTER VI: ARABIC SUMMARY.