الفهرس 
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Abstract
Summary
This thesis consists of three parts in addition to the references and Arabic summary.
Part I: Stability Indicating Methods for SimultaneoDetermination of Piracetam, Vincamine and Their Degradation Products
This part includes:
Section (A): Introduction and Literature Review This introduction describes the pharmacological action of Piracetam (PIR) and Vincamine (VINC), their chemical structure, physical properties and summary of the published methods developed for their analysis either alone or in combination with other drugs or degradation products.Section (B): Stability Indicating Multivariate Calibration Methods for Determination of Piracetam and Vincamine In this section, multivariate calibration models, such as PLS and PCR, have been successfully applied as selective stability indicating methods for determination of the quaternary mixture of PIR and VINC and their degradation products (PD and VD).To validate the predictive ability of the developed models, they were applied to predict the concentrations of PIR, VINC, PD and VD in an external validation set. Results obtained by the developed models was compared with a reported HPLC one and no significant difference was found between them.Section (C): Stability Indicating chromatographic Methods for Simultaneous Determination of Piracetam and Vincamine In this section, simple and accurate TLC-Densitometric and RP-HPLC chromatographic methods have been developed for simultaneous determination of PIR, VINC, PD and VD in their quaternary mixtures. The best separation resulted upon using chloroform: methanol: glacial acetic acid: triethylamine (8:2:0.1:0.1, by volume, pH=8.0±0.05) as a developing system and detection at 230 nm for TLC-densitometric method. While for RP-HPLC method, a mobile phase consisted of 0.05 M KH2PO4 solution (containing 1% triethylamine, pH adjusted to 3 with orthophosphoric acid): methanol (95: 5, v/v) at flow rate of 1 mL/min using C8 column and 230 nm as a detection wavelength were the optimum separation conditions. The suggested TLC-Densitometric and RP-HPLC methods were successfully applied for analysis of the cited drugs in Cervitam® capsules and the results showed good agreement with the labeled amounts and were compared to the results obtained from the reported method where no statistical difference was found.
Part II: Quantitative Determination of Dimenhydrinate, Cinnarizine and Cinnarizine Impurity in their ternary mixture
This part includes:
Section (A): Introduction and Literature Review This introduction describes the pharmacological action of Dimenhydrinate (DMH), Cinnarizine (CIN) and Cinnarizine Impurity, their chemical structure, physical properties and summary of the published methods developed for their analysis either alone or in combination with other drugs or degradation products.
Section (B): Determination of Dimenhydrinate, Cinnarizine and Cinnarizine Impurity by Different Spectrophotometric Methods In this section, different spectrophotometric methods have been investigated for determination of DMH, CIN and CIN impurity in their ternary mixture. The developed spectrophotometric methods include first derivative spectrophotometry (1D), first derivative of ratio spectra method (1DD), ratio difference spectrophotometry and mean centering of ratio spectra method (MCR).
In first derivative spectrophotometry, DMH was determined by measuring 1D amplitude at 292 nm using Δλ = 2 and scaling factor=10. In first derivative of ratio spectra method, CIN and CIN impurity were determined by measuring 1DD amplitude at 256.6 and 219.6 nm for CIN and CIN impurity, respectively, using standard spectrum of 20 μg/mL of DMH (as a divisor), Δλ = 2 and scaling factor=10. In ratio difference method, DMH was determined by measuring the ratio difference between 216.8 and 232.8 nm after using 20 μg/mL of CIN (as a divisor), While CIN and CIN impurity were determined by measuring the ratio difference between (219 and 237.2 nm) and (230 and 264 nm), respectively, after using 20 μg/mL of DMH (as a divisor). In MCR method, the second mean centered ratio spectra were obtained where peak amplitudes at maximum or minimum wavelengths were measured, So DMH, CIN and CIN impurity were determined at 240, 234.8 and 233.6 nm, respectively. Moreover, the suggested methods were applied for determination of DMH, CIN and CIN impurity in different laboratory prepared mixtures. The results obtained upon applying the proposed methods on Amocerebral® tablets were statistically compared to those obtained by applying the reported HPLC one and no significant difference was found.
Section (C): Determination of Dimenhydrinate, Cinnarizine and Cinnarizine Impurity by Different chromatographic Methods In this section, selective and accurate TLC-Densitometric and RP-HPLC chromatographic methods have been developed for simultaneous determination of DMH, CIN and CIN impurity in their ternary mixtures. The best separation resulted upon using chloroform: methanol: ammonia solution: glacial acetic acid (9.5: 0.5: 0.1:0.1, by volume, pH=9.1±0.05) as a developing system and detected at 235 nm for TLC-Densitometric method. While for RP-HPLC method a mobile phase of 0.05 M KH2PO4 solution (pH = 3 adjusted with orthophosphoric acid): methanol (35:65, v/v) as mobile phase at a flow rate of 1 mL/min using C8 column and detected at 240 nm were the optimum separation conditions. The suggested TLC-Densitometric and RP-HPLC methods were successfully applied for analysis of the cited drugs in Amocerebral® tablets and the results showed good agreement with the labeled amount and were compared to the results obtained from the reported method where no statistical difference was found.
Part III: Stability Indicating Methods for Determination of Vitamin E and Vinpocetine in Presence of Vinpocetine Degradation Product
This part includes:
Section (A): Introduction and Literature Review
This introduction describes the pharmacological action of Vinpocetine (VINP) and Vitamin E (VIT E), their chemical structure, physical properties and summary of the published methods developed for their analysis either alone or in combination with other drugs or degradation products.
Section (B): Stability Indicating Spectrophotometric Methods for Determination of Vitamin E and Vinpocetine in Presence of Vinpocetine Degradation Product
In this section, different stability indicating spectrophotometric methods have been investigated for determination of Vitamin E (VIT E), Vinpocetine (VINP) and Vinpocetine degradation product (DEG) in their ternary mixture. The developed spectrophotometric methods include dual wavelength, area under the curve combined with amplitude center method and second derivative of ratio spectra combined with isoabsorptive point method. In dual wavelength method VIT E, VINP and DEG have been determined by measuring difference in absorbance values between (217.4 and 234.4 nm), (250.4 and 314 nm) and (258.6 and 312 nm), respectively. In area under the curve method (AUC), VINP has been determined by measuring AUC of the extended spectra at 330-350 nm. In amplitude center method, the stored zero order spectra of the studied components were divided by standard spectrum of 6 µg/mL of VINP, in the obtained ratio spectra and after subtraction VINP value, DEG has been determined at 310 nm where no contribution from VIT E, While VIT E has been determined at 210 nm after multiplying by DEG correction factor. In second derivative of ratio spectra method, the stored zero order spectra of the studied components were divided by standard spectrum of 6 µg/mL of VINP, then the obtained ratio spectra differentiated using Δλ = 4 and scaling factor=100, then 2DD peak amplitude were measured at 215.2 and 237.2 nm for VIT E and DEG, respectively. In isoabsorptive point, VINP has been determined by measuring the total absorbance at λiso=264.4 nm after subtraction.
Section (C): Stability Indicating chromatographic Methods for Simultaneous Determination of Vitamin E and Vinpocetine in Presence of Vinpocetine Degradation Product
In this section, simple and accurate TLC-Densitometric and RP-HPLC chromatographic methods have been developed for simultaneous determination of VIT E, VINP and DEG in their ternary mixtures. The best separation resulted upon using methanol: chloroform: ethyl acetate: glacial acetic acid: ammonia solution (6:2:2:0.5:0.1, by volume, pH=6.5±0.05) as a developing system and detected at 235 nm for TLC-Densitometric method. While for RP-HPLC method a mobile phase of gradient elution of methanol: 0.05 M KH2PO4 solution (pH adjusted to 3 with orthophosphoric acid) at a flow rate of 1.5 mL/min using C8 column and detected at 235 nm were the optimum separation conditions. The suggested TLC-Densitometric and RP-HPLC methods were successfully applied for analysis of the cited drugs in Cavalpha® capsules and the results showed good agreements with the labeled amount and were compared to the results obtained from the reported methods where no statistical difference was found.
This thesis refers 198 references, contains 83 figures and 53 tables and ends with Arabic summary.