تصنيع ودراسة المواصفات ل الأدوية المساعده المصممة ل حمض ترانزاميك و براسيتامول
Date
2014-02-22
Authors
هبه نعيم خميس غريب
hiba naeem khamees ghareeb
Journal Title
Journal ISSN
Volume Title
Publisher
AL-Quds University
جامعة القدس
جامعة القدس
Abstract
Prodrug is a chemical devise in which the drug is covalently linked to a chemical moiety; this
linked moiety will temporarily affect the physicochemical properties of the drug for increasing
their usefulness or decreasing their toxicity. The prodrug should be converted to its active form
by metabolic or/and chemical processes, conversion process involves metabolism by enzymes
distributed throughout the body. These enzymes might either decrease the drug’s bioavailability,
or a genetic polymorphisms might lead to variability in prodrug activation and thus affect the
efficacy and safety of designed prodrug. In the past few decades computational chemistry
methods have been utilized in calculating physicochemical and molecular properties of
compounds. This tool can be used to design prodrugs that chemically (intramolecular processes)
interconvert to their parent drugs without any involvement of enzyme catalysis. The release of
the active drug is solely dependent on the rate limiting step of the intramolecular process. Based
on DFT calculations four different tranexamic acid prodrugs and three different bitter less
paracetamol prodrugs were designed, synthesized and characterized using FT-IR, 1H-NMR LCMS
and their in vitro intra-conversion to their parent drugs revealed that the t1/2 was largely
affected by the pH of the medium. For tranexamic acid ProD 1 the experimental t1/2 values in 1N
HCl, buffer pH 2 and buffer pH 5 were 54 minutes, 23.9 hours and 270 hours, respectively.
Tranexamic acid ProD 2 was readily converted in 1 N HCl and pH 2 while it was entirely stable
at pH 5 and pH 7.4. On the other hand, tranexamic acid ProD 3 and Prod 4 were stable in all
media studied. The experimental t1/2 values for paracetamol ProD 2 in pH 3 and pH 7.4 were 3
hours and 18 minutes respectively and for paracetamol ProD 3 it was 27 hours in pH 3 and 12
hours in pH 7.4. In vitro binding for paracetamol ProD 2 to bitter taste receptors revealed that
this prodrug lacks any binding affinity and it was found not to have any bitter sensation. This
suggests, that paracetamol ProD 2 can replace its parent drug, paracetamol, for the use asbitterless antipyretic drug for geriatrics and pediatrics.
Description
Keywords
العلوم الصيدلانية , Pharmaceutical Sciences