الفهرس | Only 14 pages are availabe for public view |
Abstract The present thesis includes the analytical studies for the determination of Butamirate citrate and Itopride Hydrochloride in their bulk form or pharmaceutical preparations. It comprises three chapters: Chapter I: contains an introduction on Butamirate citrate (BC), Itopride hudrochloride (IT) and on the proposed methods for their determination, and also includes literature survey on the methods reported for their determination and on the selected methods for their analysis. Chapter II: contains the experimental part which includes the materials, preparation of various solutions, apparatus used and general procedures for the developed methods for the determination of BC and IT. Chapter III: contains the results and discussion, which contains the proposed methods for the determination of BC and IT, and includes two parts: Part 1: This part describe selective RRLC and HPLC, used for the determination of butamirate citrate in raw material, in pharmaceutical formulations and in presence of its acid–and alkaline-degradates, and determination of Itopride HCl (IT) with Pantoprazole Na (PA) as amixture, These methods proved that the selectivity, accuracy, and simple mobile phases used provide simple and economic applications, and they reflect suitability for quality control laboratories. The proposed methods permit the preparations of BC degradate and IT in pure form within a short time at room temperature. 132 i) RRLC and HPLC Methods for determination of BC: The proposed RRLC and HPLC methods were developed and validated for sensitive and specific quantitative analysis of BC in its available commercial syrup with no interference from the excipients or its degradation product. As well, the solvents used in preparation of mobile phases are available in all analytical laboratories. A potential advantage appears in the study of reaction kinetics of the degradation and was found to be a pseudo-first-order reaction under the experiment’s basic and acidic stress conditions, while the half-life times were estimated. Moreover, the thermodynamic parameters of acid degradation reaction and activation energies were estimated for its importance in understanding and optimizing molecular interactions and design process. Rapid resolution liquid chromatography (RRLC) Agilent SB-C18 (4.6×50 mm, 1.8μm) column with mobile phase [0.2% triethylamine bufer: acetonitrile (50:50 v/v)], pH 4.8 adjusted with phosphoric acid and ultraviolet detection at 222 nm. HPLC Promosil C18 (4.6 mm×250 mm, 5μm) column with mobile phase [0.05 M ammonium dihydrogen phosphate bufer: acetonitrile 50:50 (v/v)] with pH 5.4 and ultraviolet detection at 222 nm. These methods showed high sensitivity concerning linearity, accuracy, and precision over the range from 5 to 150 μgmL−1 and 1 to 150 μgmL−1 for RRLC and HPLC methods, respectively ii) RRLC Method for determination of IT: RRLC method was applied for the determination of Itopride hydrochloride (IT) drug with pantoprazole sodium (PA) as mixture, using Bonus- RP C18, (1.8 μm, 4.6x50 mm) column; mobile phase: (0.02% ammonium formate buffer: methanol (50:50 v/v), pH 5.6 adjusted with formic acid. Linearity range from 2-180 μgmL-1 of IT and from 1.6-32 μgmL−1 of PA were prepared from working solution and 5μL injected (triplicate) for RRLC method, and chromatographed at 280 nm under the previously described chromatographic conditions. The average peak areas were 133 calculated and plotted against the corresponding concentration of the drug in μgmL-1and the regression equation was computed. Part 2: In this part, the proposed carbon paste electrodes based on butamirate-phosphomolybdate, butamirate-phosphotangestate and itopride-phosphotangestate as the electroactive compounds might be a useful analytical tool and an interesting alternative in the determination of BC and IT in the bulk form and pharmaceutical formulation. The present electrodes show high sensitivity, reasonable selectivity, long-term stability and applicability over a wide pH range. The reported methods are simple, sensitive, highly specific and advantageous over the previously described procedures for BC and IT determinations, because interferences from the recipients, impurities, degradation products or other accompanying drug components are eliminated. The carbon paste electrode has the advantage of being easy to prepare and regeneration of the active surface. i) Carbon paste method for determination of BC: The utility of carbon paste electrode for the determination of butamirate citrate modified with butamirate–phosphomolbdic acid (B-PM) and butamirate-phosphotungestic acid (B-PT) ion-associates in batch mode is demonstrated. The electrodes revealed a Nernstian response over a wide concentration ranges 1.99×10-5 -1x10-2 mol L-1 and 9.99×10-6 -1x10-2 molL-1 using B-PM and B-PT, respectively. The detection limits of these electrodes are 3.38×10-6 molL-1, and 1×10-5 mol L-1 using B-PM and B-PT, respectively. The best electrode performance was obtained with carbon paste composition of 5% butamirate -phosphomolybdate, 47.5% graphite and 47.5% di octylphthalate (DOP) and 10% butamirate -phosphotungestate, 45% graphite and 45% dioctyl phethalate (DOP). The sensors exhibit response time (8-22 s) and (8-19 s) for B-PM and B-PT, respectively. They have good selectivity in presence of inorganic cations, and amino acids. The electrodes were successfully applied to monitoring of butamirate citrate in pure solution and 134 pharmaceutical formulation (cough cut syrup 7.5 mg/5mL). The recovery ranges using the standard addition method were found from 98.21–103.11% and 99.59-102.60% using B-PM electrode and 98.06–101.03% and 99.05-100.80% using B-PT electrode, respectively, the recovery ranges using Calibration curve method were found from 97.27-99.05% using B-PM electrode and 100.09- 101.90% using B-PT electrode. ii) Carbon paste method for determination of IT: Different carbon paste sensors were prepared by varying the percentages of the ion-exchanger (IT-PT) and using different solvent mediators to obtain the optimum compositions of the sensors which give the best performance characteristics. The electrodes revealed a Nernstian response over a wide concentration ranges 1.39×10-5- 1.00x10-2 molL-1. The detection limit of this electrode is 3.23×10- 6mol L-1. The best electrode performance was obtained with carbon paste composition of 10% itopride-phosphotungestate, 45% graphite and 45% dioctyl phethalate (DOP). The sensors exhibit response time (5-10 s). It has good selectivity in presence of inorganic cations, and amino acids. The electrode was applied to monitoring of itopride hydrochloride in pure solution and pharmaceutical formulation (Garopride 50 mg tablets). The recovery ranges using the standard addition method were found from 99.79–100.50% and 99.84-101.01%, the recovery ranges using Calibration curve method was found from 97.24- 101.94%.The sensor of the optimum composition was used directly to carry out all the subsequent studies without any soaking. Summary: both Arabic and English summary are given by the end of the thesis. References: contains all references used in the thesis which were of a great help to this study. |