Thesis (Ph.D.) – Cairo University. Faculty of Pharmacy. Department of Pharmaceutical Chemistry.

Four simple, accurate, sensitive and economic Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopic (ATR-FTIR) methods have been developed for the quantitative estimation of some non-steroidal anti-inflammatory drugs alone or in presence of related substances. The first method involves the determination of etodolac by direct measurement of the absorbance at 1716 cm-1. In the second method, the second derivative of the IR spectra of tolfenamic acid and its imperity (2-chlorobenzoic acid) was used and the amplitudes were measured at 1084.27 cm-1 and 1058.02 cm-1 for tolfenamic acid and 2-chlorobenzoic acid, respectively. The third method used the first derivative of the IR spectra of bumadizone and its reported degradation product, N,N-diphenylhydrazine and the amplitudes were measured at 2874.98 cm-1 and 2160.32 cm-1 for bumadizone and N,N-diphenylhydrazine, respectively. The fourth method depends on measuring the amplitude of diacerein at 1059.18 cm-1 and of rhein, its reported degradation product, at 1079.32 cm-1 in their first derivative spectra. The four methods were successfully applied on the pharmaceutical formulations by extracting the active constituent in chloroform and the extract was directly measured in liquid phase mode using a specific cell. Moreover, validation of these methods was carried out following International Conference of Harmonisation (ICH) guidelines.

Synthesis of new derivatives through an esterification reaction between the carboxylic acid functional group in NSAIDs and a naturally occurring phenolic antioxidant, thymol, to give anew prodrug. This is one of possible approaches to solve GIT irritation problem. The suggested prodrugs to be prepared are Etodolac-thymol and Tolfenamic acid-thymol prodrugs. The new prodrugs structure should be confirmed by FT-IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis. After synthesis and structure confirmation, the prodrugs will be evaluated for their chemical stability in different temperatures and pHs. Moreover, a kinetic study in 20% liver homogenate and 10% buffered plasma would be carried based on RP- HPLC method for the separation and determination of the 2 new prodrugs and their related bioactive products.

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