التركيب الكيميائي والخصائص والقوى المحركة المخبرية لدوائيْن أوليّيْن جديديْن مبتكريْن من مضادات البكتيريا؛ الأموكسيلين والسيفالكسين
Date
2014-02-22
Authors
غدير عبد مطر دقماق
GHADEER ABED MATAR DOKMAK
Journal Title
Journal ISSN
Volume Title
Publisher
AL-Quds University
جامعة القدس
جامعة القدس
Abstract
Marketed antibacterial drugs suffer several problems, such as bitter taste and low stability
which lead to patient incompliance. Prodrug technology for solving such problems is
extremely exciting. Based on previously reported density functional theory calculations,
amoxicillin ProD 1-2 and cephalexin ProD 1-2 were designed and synthesized. For the
intraconversion of both antibacterial prodrugs the kobs and t1/2 values in different media
were calculated from the linear regression equation obtained from the correlation of log
concentration of the residual prodrug versus time. At constant temperature and pH the
hydrolysis reaction for the above mentioned prodrugs displayed strict first order kinetics as
the kobs was quite constant and a straight line was obtained. Kinetic studies in 1N HCl, pH
2.5 and pH 5 were selected to examine the intraconversion of both prodrugs to their parent
drugs. The acid-catalyzed hydrolysis of the prodrugs was found to be much higher in 1N
HCl than in pH 2.5 and pH 5. The experimental t1/2 values of amoxicillin ProD 1 in 1N
HCl, pH 2.5 and pH 5 were 2.5, 7 and 81 hours respectively and for cephalexin ProD 1 in
1 N HCl and pH 2.5 were 2 and 14 hours respectively. In contrast, t1/2 values of amoxicillin
ProD 2 in 1N HCl and pH 2.5 were 8 and 44 hours respectively and for cephalexin ProD 2
in 1 N HCl was 6 hours. On the other hand, at pH 7.4, the four prodrugs were quite stable
and no release of the parent drugs was observed. At pH 5 the hydrolysis of the prodrugs
was too slow. The four antibacterial prodrugs were found to be bitterless. The bitter taste
masking by the prodrugs is believed to be via altering the ability of the drug to interact
with bitter taste receptors.
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Keywords
العلوم الصيدلانية , Pharmaceutical Sciences