تصنيع ودراسة لمواصفات الأدوية المساعدة المصممة لمادة الغايفينيسين
Date
2014-02-25
Authors
أمين محمود عبد المنعم ثوابته
Amin Mahd A. Thawabteh
Journal Title
Journal ISSN
Volume Title
Publisher
AL-Quds University
جامعة القدس
جامعة القدس
Abstract
Guaifenesin is an extremely bitter taste substance which affects its usage in pediatric and
geriatric formulations. In this thesis we aimed to mask the bitter taste of guaifenesin by
converting it to a potential tasteless prodrugs using different linkers. The prodrugs were
synthesized by esterification of carboxylic acid anhydrides and guaifenesin. Maleic
anhydride, succinic anhydride, and glutaric anhydride, respectively, were used to
synthesize guaifenesin ester prodrugs (guaifenesin maleate, guaifenesin succinate,
guaifenesin glutarate), 1 H-NMR, LC-MS, and FT-IR have confirmed the identity and
purity of the new prodrugs.
In vitro kinetic studies for the above mentioned prodrugs were done in four different
aqueous media: 1 N HCl and buffers pH 3.3, pH 5.5 and pH 7.4. Under the experimental
conditions the target prodrug was hydrolyzed to release the parent drug, guaifenesin, as
was confirmed by HPLC determination. The kobs and the corresponding t1/2 values for
guaifenesin prodrugs in 1N HCl were calculated from the linear regression equation
correlating the log concentration of the prodrug versus time. The rate constant (kobs) was
found to be 7.2x10-4
for guaifenesin maleate prodrug, 2.54x10-4
guaifenesin succinate
prodrug, and 2.36x10-4
guaifenesin glutarate prodrug. Half-lives values (t1/2) were 2.01
hours for guaifenesin maleate prodrug, 7.03 hours for guaifenesin succinate prodrugs, and
7.17 hours for guaifenesin glutarate prodrug. On the other hand, at pH 3.3, 5.5 and 7.4,
guaifenesin maleate, guaifenesin succinate, and guaifenesin glutarate prodrugs were
entirely stable and no release of the parent drug, guaifenesin, was observed.
Description
Keywords
العلوم الصيدلانية , Pharmaceutical Sciences