الفهرس 
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Abstract
Aim of the work
The aim of the present work is to develop analytical methods
(potentiometric and spectrophotometric methods) for study and quantitative
determinations of some anti-histaminic drugs [hydroxyzine hydrochloride
(HYZ), meclozine hydrochloride (MOZ) and cinnarizine (CIZ)].
The present thesis comprises of three chapters:
Chapter (1)
Contains two parts:
The first part includes general introduction concerning theoretical bases of the
general properties of different types of ion selective electrodes and great
attention was given to the applications of ion selective electrodes in
pharmaceutical analysis. Also include basic spectrophotometry, theory, concepts
and applications.
The second part gives a literature survey of the previous studies for the analysis
of the studied drugs including spectrophotometric, potentiometric,
chromatographic, and electrophoresis methods.
Chapter (2)
Contains two parts:
The first part is experimental part for ion selective electrode which dealing with
the materials, reagents and instruments used as well as the experimental
techniques applied. Full details are given for the preparation of the electrodes,
construction of the calibration graphs and investigation of the effect of response
time, and pH on the performance characteristics of the electrodes, also methods
for evaluation of the electrode selectivity and determination of the studied drug
in pure solutions and in its pharmaceutical formulations.
The second part deals with experimental part for spectrophotometric technique
which includes apparatus used for measurements and procedures for preparation
of drug and reagent solutions. It is also contains the proposed
spectrophotometric methods for determination of the studied drugs in pure and
in dosage forms.
Chapter (3)
Contain two parts:
The first part: deals with the results and discussion for potentiometric technique
used ion selective electrodes for the determination of the studied drugs in which
sodium 12-tungstophosphate (TP), ammonium reineckate (AR) and ammonium
molbydate (AM) anions were tested as ion-pair agents for the preparation of
electroactive ion association complexes of studied drugs. Sensors incorporating
membranes with PVC as a plastic matrix, dioctyl phthalate as a solvent mediator
and studied drug ion-pair were prepared and electrochemically evaluated.
The following experimental variables were investigated.
1. Effect of acidity.
2. Study of response time.
3. Interference.
The performance characteristics and uses of the proposed electrodes were fully
discussed in terms of.
• The usable concentration ranges of the studied drugs 1×10-2 - 1×10-7 M with
(sodium 12-tungstophosphate, ammonium reineckate and ammonium molbydate)
and 1×10-2 - ×10-6 M in case of ammonium reineckate with meclozine
hydrochloride and cinnarizine.
• The effect of soaking life time of the electrodes.
• The effect of pH changes on the electrodes performance. The potential
variations due to pH changes are considered acceptable in the pH ranges of (2.5-
6.5, 3.0-6.5 and 2.5-7.0) for hydroxyzine HCl, (4.0-7.0, 4.0-6.0 and 3.0-7.0) for
meclozine HCl and (3.0-7.0, 2.5-6.5 and 3.0-7.0) for cinnarizine with (sodium
12-tungstophosphate, ammonium reineckate and ammonium molbydate),
respectively.
• The response time of the electrode, which is the time required to achieve a
steady state potential (within ±1mV) after successive immersion of the
electrodes in a series of the drug solution, each having a 10-fold increase in
concentration. The electrodes yielded steady potential within 10-20 s.
• The selectivity of the electrodes towards different substances and ionic species
was checked and the values of the selectivity coefficient were calculated to
evaluate their degree of interferences. The obtained values indicating that the
present electrodes have high ability to discriminate between the tested drug
cation and interfering substances
• Analytical applications which involve determination of the studied drug using
their selective electrodes in different samples applying standard addition method
and potentiometric titration.
• The results are in high agreement with those obtained using the official
methods as clear from the statistical treatment of the results obtained from the
analytical applications using F-test and t-test
The second part: contain the results and discussion for spectrophotometric
procedures for the determination of the studied drugs using acid dyes reagents
bromocresol green (BCG), bromocresol purple (BCP), bromophenol blue (BPB)
and rose Bengal (RB). The proposed method are based on colored ion-pair
complex formation between the acid dyes and drugs which is extracted with
organic solvent except for rose bengal, (chloroform, carbon tetrachloride,
methylene chloride, hexane and benzene) and determination of the concentration
by measuring the absorbance of the extracted complex against a blank prepared
by the same way except addition of the drug. The following experimental
variables were investigated.
1. Effect of acidity.
2. Effect of time.
3. Effect of the extracting solvent.
4. Effect of reagent concentration.
5. Suggested mechanism.
6. Interference.
7. Validity of the method.
Beer’s law is obeyed within the concentration ranges (2.5-40.0, 2.5-37.5,
5.0-62.5 and 2.0-15.0 μg ml-1) for hydroxyzine HCl, (5.0-45.0, 2.5-45.0, 2.5-
37.5 and 2.0-20.0 μg ml-1) for meclozine HCl and (2.5-30.0, 5.0-45.0, 2.5-25.0
and 2.0-25.0 μg ml-1) for cinnarizine, in case of (BCG, BCP, BPB and RB)
respectively. For more accurate results, ringbom optimum concentration ranges
are determined. Molar absorbtivity, sandell sensitivity, detection and
quantification limits are calculated. In order to determine the accuracy and
precision of the proposed methods, solutions containing three different
concentrations of the studied drugs are prepared and analysed in six replicates.
The recovery, relative standard deviations, relative error and confidence limits
are calculated. The proposed methods can successfully applied to determine the
pure form of the studied drugs and their dosage forms. The results obtained from
studied drugs are compared statistically drugs and their dosage forms. The
results obtained are compared statistically by student’s t-value and variances
ratio F-test with the official methods at 95% confidence level. The results show
that t- and F-values are less than the critical value indicating that there is no
significant difference between the proposed and official methods. Thus, the
proposed spectrophotometric method can be applied in determination of the
studied drugs in pure form and in dosage forms.