Analytical Study Of Some Anti-histaminic Drugs:

Ahmad Hamdy Ahmad Mohammed

Aim of the workThe aim of the present work is to develop analytical methods(potentiometric and spectrophotometric methods) for study and quantitativedeterminations 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 thegeneral properties of different types of ion selective electrodes and greatattention was given to the applications of ion selective electrodes inpharmaceutical analysis. Also include basic spectrophotometry, theory, conceptsand applications.The second part gives a literature survey of the previous studies for the analysisof 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 withthe materials, reagents and instruments used as well as the experimentaltechniques applied. Full details are given for the preparation of the electrodes,construction of the calibration graphs and investigation of the effect of responsetime, and pH on the performance characteristics of the electrodes, also methodsfor evaluation of the electrode selectivity and determination of the studied drugin pure solutions and in its pharmaceutical formulations.The second part deals with experimental part for spectrophotometric techniquewhich includes apparatus used for measurements and procedures for preparationof drug and reagent solutions. It is also contains the proposedspectrophotometric methods for determination of the studied drugs in pure andin dosage forms.Chapter (3)Contain two parts:The first part: deals with the results and discussion for potentiometric techniqueused ion selective electrodes for the determination of the studied drugs in whichsodium 12-tungstophosphate (TP), ammonium reineckate (AR) and ammoniummolbydate (AM) anions were tested as ion-pair agents for the preparation ofelectroactive ion association complexes of studied drugs. Sensors incorporatingmembranes with PVC as a plastic matrix, dioctyl phthalate as a solvent mediatorand 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 fullydiscussed 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 meclozinehydrochloride and cinnarizine.• The effect of soaking life time of the electrodes.• The effect of pH changes on the electrodes performance. The potentialvariations 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) formeclozine HCl and (3.0-7.0, 2.5-6.5 and 3.0-7.0) for cinnarizine with (sodium12-tungstophosphate, ammonium reineckate and ammonium molbydate),respectively.• The response time of the electrode, which is the time required to achieve asteady state potential (within ±1mV) after successive immersion of theelectrodes in a series of the drug solution, each having a 10-fold increase inconcentration. The electrodes yielded steady potential within 10-20 s.• The selectivity of the electrodes towards different substances and ionic specieswas checked and the values of the selectivity coefficient were calculated toevaluate their degree of interferences. The obtained values indicating that thepresent electrodes have high ability to discriminate between the tested drugcation and interfering substances• Analytical applications which involve determination of the studied drug usingtheir selective electrodes in different samples applying standard addition methodand potentiometric titration.• The results are in high agreement with those obtained using the officialmethods as clear from the statistical treatment of the results obtained from theanalytical applications using F-test and t-testThe second part: contain the results and discussion for spectrophotometricprocedures for the determination of the studied drugs using acid dyes reagentsbromocresol green (BCG), bromocresol purple (BCP), bromophenol blue (BPB)and rose Bengal (RB). The proposed method are based on colored ion-paircomplex formation between the acid dyes and drugs which is extracted withorganic solvent except for rose bengal, (chloroform, carbon tetrachloride,methylene chloride, hexane and benzene) and determination of the concentrationby measuring the absorbance of the extracted complex against a blank preparedby the same way except addition of the drug. The following experimentalvariables 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, 2.5-25.0and 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 rangesare determined. Molar absorbtivity, sandell sensitivity, detection andquantification limits are calculated. In order to determine the accuracy andprecision of the proposed methods, solutions containing three differentconcentrations of the studied drugs are prepared and analysed in six replicates.The recovery, relative standard deviations, relative error and confidence limitsare calculated. The proposed methods can successfully applied to determine thepure form of the studied drugs and their dosage forms. The results obtained fromstudied drugs are compared statistically drugs and their dosage forms. Theresults obtained are compared statistically by student’s t-value and variancesratio F-test with the official methods at 95% confidence level. The results showthat t- and F-values are less than the critical value indicating that there is nosignificant difference between the proposed and official methods. Thus, theproposed spectrophotometric method can be applied in determination of thestudied drugs in pure form and in dosage forms.