this ppt give you some basic idea how a prodrug can increase the membrane permeability.

1. Presentation on prodrug
 Submitted by
Keshob kumer Ghose
ID: 2016000300001
Elvin Akhter Mim
ID: 2016000300004
Tabassum Roshny
ID: 2016000300006
Elit Hasan Rakib
ID: 20160003000008
 Submitted to
Surid Mohamod Chowdhury
Lecturer, Dept. of pharmacy,
SEU

2. prodrug
Improvement of membrane permeability

3. Prodrug?
 A medication or compound that after
administration, is metabolized into a
pharmacologically active drug.
 Sulfasalazine has to be broken down by bacteria in
the colon into two products- 5 amino salicylic acid
and sulfa pyridine.

4. Fact
 The oral bioavailability of a drug may be limited by
its
Aqueous solubility
Low solubility
Both rapid and extensive hepatic metabolism

5. Needs of prodrug
 Improve patient acceptability.
 Alter and improve absorption.
 Alter bio distribution.
 Alter metabolism.
 Alter elimination.
 Drug is not sufficiently bioavailable.
 Drug does not permit the BBB.
 Drug has no organ or cell specificity.

6. Structure of cell membrane

7. Dosage form
 If oral……form stomach and intestine to portal
circulation.
 If pre-rectal ……from rectum to systemic circulation.
 If intramuscular……from muscle to systemic
circulation.
So for absorption drug needs crossing of the cell
membrane

8. How
 Since unafacilated and largely nonspecific passive
transport mechanisms are the most common
absorption routes in oral drug delivery, better
diffusion across the biologic phospholipid bilayers,
and thus better oral bioavailability can be achieved
by increasing the lipophilicity of an active agent by
masking polar ionized or nonionized functional
groups.

9. example
 Oseltamivir Is an orally active prodrug of
oseltamivir carboxylate (selective inhibitor of viral
neuraminidase).
 As an ethyl ester, oseltamivir is both rapidly and
well absorbed and this modification increase the
oral bioavailability.

10. oseltamivir

11. How
 An alternative means of increasing oral absorption
of a drug is carrier mediated transport, which is
particularly important where a drug is either polar
or charged and where passive transcellular
absorption is negligible.
 A number of prodrug s have been designed to
structural features that would allow them to be
recognized and taken up by these transporters.

13. example
 Midodrine, which is an prodrug of
desglymidodrine, a selective alpha-1 receptor
agonist for the treatment of orthostatic
hypotension.
 Midodrine contains a glycine promoiety that is
attached to the amine functionally of DMAE, and it
is converted into its parent active drug primarily in
the liver and In the systemic circulation by unknown
peptidase.

14. Midodrine

15. valacyclovir
 Valacyclovir is a L-valyl ester prodrug of acyclovir, a
purine nucleoside used for the treatment of herpes
virus infections. Valacyclovir is a substrate, not only
for peptide transporter 1 but also for Na-
dependent neutral amino acid transporter. After
absorption, it is bio activated by valacyclovir
hydrolase. The bioavailability of this prodrug is
more than 50%, which is 20 to 35% better than the
bioavailability of acyclovir.

16. valacyclovir

17. How
• Lipophilicity of poorly permeable drugs can be
increased by modifying the hydrocarbon moieties.
Lipophilicity can be achieved by masking polar
ionized or nonionized functional groups to
enhance oral absorption.

19. THANK YOU