الفهرس 
Introduction and Literature Survey
Butamirate citrateOnly 14 pages are availabe for public view
 |  | from | 188 |  |  |
| | | from | 188 | | |
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.