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العنوان
Analytical Study of Some Compounds of Pharmaceutical Interest Possessing Acidic Groups or Their Derivatives /
المؤلف
Abo Gharam, Amira Hany El Saeed Ebrahim.
هيئة الاعداد
باحث / اميره هانىء السعيد ابراهيم
مشرف / مجدى محمد عبد الخالك
مشرف / هدى محمد جمال الدين دعبيس
مشرف / هبه حسن عابدين
الموضوع
Pharmaceutical Chemistry. Acidic Groups.
تاريخ النشر
2020.
عدد الصفحات
288 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
العلوم الصيدلية
تاريخ الإجازة
1/1/2020
مكان الإجازة
جامعة الاسكندريه - كلية الصيدلة - كيمياء صيدليه
الفهرس
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Abstract

The thesis deals with the analysis of some drugs whose chemical structures contain acidic group(s) or their functional derivatives.
The studied drugs in the thesis belong to different pharmacological classes such as non steroidal anti-inflammatory agents, adrenergic agents, leukotriene and proton pump inhibitors.
The thesis consists of six parts:
Part I This part presents a general introduction about the chemical names, structures, physical properties, pharmacological actions and therapeutic uses of the studied drugs.
Besides, it summarizes the pharmacopoeial and other published analytical methods for the selected drugs in pharmaceutical dosage forms, biological samples and other possible matrices.
Part II This part deals with two novel and eco-friendly chromatographic methods for the simultaneous quantification of bambuterol hydrochloride and montelukast sodium in presence of terbutaline as the pharmacopeial related substance of bambuterol hydrochloride.
The first method is HPLC-DAD procedure with the aid of Zorbax eclipse plus C8 column(4.6 x 250 mm, 5 μm particle size)as a stationary phase and a mobile phase consisting of a mixture of0.003M phosphate buffer pH 5.0 and acetonitrile eluted in a gradient mode at a constant flow rate of 1.1 mL/min.
The chromatograms were recorded at 210 nm for the three cited drugswhere the analyte peaks eluted at retention times 2.867, 8.615and 12.339 min for terbutaline, bambuterol and montelukast, respectively.
The second method is HPTLC procedure using precoated HPTLC silica gel aluminum plates 60 F254with a mobile phase system consisting of ethyl acetate, ethanol and ammonia (78.9: 12: 9.1).
The developed plates were scanned densitometrically at 210 nm for the three analytes where compact spots of montelukast, terbutaline and of bambuterol were observed at Rfvalues of 0.30, 0.40 and 0.60,respectively.
Analytical performance of the adopted methods was validated according to the ICH guidelines with respect to linearity, ranges, precision, accuracy, robustness, detection and quantification limits.
Excellent linearity of the developed methods is proved by the high values of regression coefficients (not less than 0.9993).
The adopted methods were successfully applied for the concurrent analysis of bambuterol and montelukast in their combined tablets.
Moreover, statistical comparison of the results of the proposed chromatographic methods and those of the greenest reference method was applied using the one-way analysis of variance test(Single factor ANOVA) where no significant differences were noted. Finally, claiming greenness according to authors‘ assumptionsis not sufficient, therefore greenness assessment using four approaches; analytical Eco-Scale, the national environmental methods index (NEMI), Raynie pictogram and green analytical procedure index(GAPI)was performed to confirm the greenness of the proposed HPLC and HPTLC methods and also to rank and compare the green character of the proposed and previously published chromatographic methods.
Part III This part includes the development and validation of versatile HPLC-DAD and HPTLC methods for the concurrent quantitative estimation of five drugs namely, diacerein, aceclofenac, diclofenac sodium, celecoxib and meloxicam within a single run in a short analysis time.
For HPLC-DAD, effective separation was performed through using Zorbax SB C18 (4.6 x 250 mm, 5 μm particle sizes) with the mobile phase composed of 0.05 M phosphate buffer pH 3.0 and acetonitrile (42:58) and pumped isocratically ataflowrate of 1 mL/min. The chromatograms were extracted at 258 nm for diacerein and celecoxib,at 276 nm for aceclofenacand diclofenac and at 355 nm for meloxicam.
The cited drugs were well resolved with retention times 3.816, 5.281, 7.611, 8.322 and 9.875 min for diacerein, meloxicam, aceclofenac, diclofenac and celecoxib, respectively.
In HPTLC procedure, precoated TLC silica gel aluminum plates 60 F254(10 x 10 cm) were used with a mobile phase consisting of mixture of 92% chloroform, 8% methanol and 0.25% glacial acetic acid.
The developed plates were scanned densitometrically at 258 nm for diacereinand celecoxib, at 280 nm for aceclofenacand diclofenacand at 360 nm for meloxicam.Well resolved peaks of the investigated drugs appeared at Rf values of 0.27, 0.37, 0.61, 0.67and 0.74for aceclofenac, diacerein, diclofenac, celecoxiband meloxicam, respectively.The validation of the proposed methodswas evaluated based on ICH guidelines for linearity, ranges, precision, accuracy, robustness, detection and quantification limits.
Good linearities for the proposed methods were verified by high correlation coefficients (r 0.9992).The adopted methods are successfully applied to the assay of different diacereinbinary mixtures in their combined dosage forms with satisfactory level of selectivity, accuracy and precision.
In addition for each binary mixture, analysis results of the proposed chromatographic methods were statistically compared with those obtained from the reference method using the one way analysis of variance test (Single-factor ANOVA) where the calculated F-values did not exceed the critical value, revealing no substantial differences between the proposed and reference methods.
Finally, the calculation of the analytical Eco-scales was performed to confirm the greenness of theproposed methods and to compare them with the different reported HPLC and HPTLC methods.
Part IV This part describes the establishment of four analytical methods for the concomitant determination of diacerein and meloxicam including two stability indicating chromatographic methods and two spectrophotometric techniques.
This part includes two chapter.