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العنوان
APPLICATION OF STABILITY STRESS TESTING ON SOME PHARMACEUTICAL FORMULATIONS
المؤلف
Magdy Hanna Nassif,Nancy
هيئة الاعداد
باحث / Nancy Magdy Hanna Nassif
مشرف / Laila El-Sayed Abd El-Fattah
مشرف / Maha Farouk Abd El-Ghany
مشرف / Ahmed Ashour Abd El Wahab
الموضوع
Capillary Electrophoresis-
تاريخ النشر
2010
عدد الصفحات
271.p:
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
العلوم الصيدلية
تاريخ الإجازة
1/1/2010
مكان الإجازة
جامعة عين شمس - كلية الصيدلة - Pharmaceutical Analytical Chemistry
الفهرس
Only 14 pages are availabe for public view

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from 271

Abstract

The thesis includes four parts:
Part I: General Introduction and Literature Review
This part comprises a brief idea about different ICH guidelines and the proposed stress testing conditions. The studied proton pump inhibitors, their structures, properties and stability, together with a summary of different methods reported in the literature for their determination are also given.
Part II: Stability-Indicating TLC-Spectrodensitometric Methods for the Determination of Pantoprazole and Lansoprazole
In this part, the quantitative determination of Panto and Lanso in pure form, in pharmaceutical formulations and in six stressed samples (acid, alkaline, oxidative-induced degradation, wet thermolysis, dry thermolysis and photodegradation) were successfully achieved using mobile phases consisting of chloroform: methanol: ammonia 33%: acetonitrile (30: 3: 0.5: 13, by volume) and chloroform: isopropanol: ammonia 33%: acetonitrile (18: 5: 0.8: 8 , by volume) for Panto and Lanso, respectively.
The two drugs were found to be degraded in acid, alkaline, neutral and oxidative medium. They are also thermolabile. Panto and Lanso show no degradation when exposed to UVA and white cool fluoresecent lamp but they are degraded when exposed to direct sunlight.
The methods were validated and compared statistically with a reported method.
Part III: Stability-Indicating HPLC Methods for the Determination of Pantoprazole and Lansoprazole
Section A: HPLC Determination of Pantoprazole and Lansoprazole
This section includes the determination of Panto and Lanso using reversed phase HPLC with UV detection at 290 and 285 nm, respectively. The chromatographic separation was achieved using mobile phases of potassium dihydrogen phosphate: acetonitrile in a ratio 100:50 v/v and 100:60 v/v for Panto and Lanso, respectively.
Linear correlation were obtained between the peak area and the corresponding concentrations of Panto and Lanso within the concentration range 0.40 - 50.00 μg/mL and 0.80 – 35.00 μg/mL; for Panto and Lanso, respectively.
The proposed methods were successfully applied for the determination of the proposed drugs in their pharmaceutical formulations and the accuracy was assessed by applying the standard addition technique.
Statistical comparison of the obtained results was adopted relative to those obtained by applying the reported method and no significant difference was found between the two methods.
Section B: Kinetic Studies of Acid, Alkaline and Oxidative-Promoted Degradation for Pantoprazole and Lansoprazole.
In this section the order of acid, alkaline and oxidative-induced degradation reactions for both drugs were studied using the isolation method. The order of the reaction was found to be pseudofirst order. The study shows that Lanso was more susceptible to all these types of degradation than Panto.
Part IV: Simultaneous Spectrophotometric Determination of Pantoprazole, Amoxicillin and Metronidazole.
This part describes three spectrophotometric methods for the simultaneous determination of the co-adminstered drugs; Panto, Amox and Metro.
In the derivative ratio spectra-zero crossing method, Panto was determined at 301nm and Amox at 245.2nm, using a solution of Metro of concentration 25 μg/mL as divisor. Metro was determined at 235.8 nm using a solution of Panto of concentration 5μg/ml as divisor.
In the double divisor ratio derivative method, Panto was determined at 299nm (20μg/mL Amox + 20 μg/mL Metro as divisor), Amox was determined at 243nm (15μg/mL Panto + 15 μg/mL Metro as divisor) and Metro was determined at 240nm (15μg/mL Panto + 15 μg/mL Amox as divisor).
In the chemometrics-assisted double divisor ratio derivative method using Savitsky-Golay function, Panto was determined at 298nm, Amox at 242nm and Metro at 240nm.
The proposed methods were applied for the determination of the three drugs in pure form, in pharmaceutical preparations, in laboratory prepared mixtures and in spiked plasma.
Part V: Refrences.
This thesis contains 140 refrences