1.21 Formation of ternary complexes
a water soluble polymer and CD and a drug mixed together in a solution to
obtain the so called ternary complexes, it is possible increase to drug
solubilization, when compared to the polymer and CD separately, which is a
result of the synergistic effect between the components. Formulations
containing drug: CD complexes with the addition of a water soluble polymer have
proven to be capable of increasing the bioavailability of formulations while
reducing the amount of CD by up to 80% 73. In the presence of water, the polymer aids in the wettability of
particles resulting in the accelerated dissolution and increased amount of drug
delivered in vitro 74.
interaction of water – soluble polymers with drug may occur by means of ion –
ion, ion – dipole, dipole – dipole electrostatic bonds, Vander Waals force, or
3 –center, 2 – electron bonds 75. Similarly the interaction between polymers and CDs and drug: CD
complexes begins to occur on the external surface of the CD molecule. CDs
polymers and drug: CD complexes form aggregates capable of solubilizing drugs
and other hydrophobic molecules 76, as shown in figure.
Figure 4: Representation of
ternary complex formation between drugs, CD and water soluble polymer
3 – Acetyl Coumarin ( 3AC)
Coumarins and their derivatives form an elite class
of compounds, occupying an important place in the realm of natural products and
synthetic organic chemistry 77.
3-acetyl-coumarins are important initial compounds for the synthesis of
coumarins and the synthesis of coumarins and their derivatives has attracted
considerable attention from organic and medicinal chemists for many years as a
large number of natural products contain this heterocyclic nucleus.
Coumarin (benzopyrones or 2-oxo-2H-chromene) is a compound containing two structures of
six member heterocyclic rings with two oxygen atoms. Classification of
coumarins includes simple coumarin, furanocoumarins, pyranocoumarins and coumarins substituted in
the pyrone ring 78.
Simple coumarins are compound that undergoes hydroxylation, alkoxylation and
alkylation to form its derivatives. Coumarin can be found in several plants
notably with high concentration in the tonka bean (Dipteryx odorata), vanilla
grass (Anthoxanthum odoratum), woodruff (Galium odoratum), mullein (Verbascum spp.), and sweet grass (Hierochloe odorata). It
has a sweet scent, readily recognized as the scent of newly mown hay, and has been used in perfumes since 1882.
Natural coumarin compounds can be found in flowers, seeds, fruits, trunk, stem
and foliage and suitable solvents can be used in extraction for its isolation.
Coumarins also can be produced through organic synthesis although it can be
found naturally in several green plants. The 3-Acetylcoumarin is also known as 2H-1-Benzopyran-2-one or 3-Acetyl-2H-chromen-2-one.
exists in two polymorphic forms i.e. form A (Triclinic) and
form B (Monoclinic).
Structure of 3AC
of. 3AC is C11H8O3.
5: Structure of 3-AcetylCoumarin
1.24 Synthesis of 3AC
3-Acetylcoumarin was prepared according
to the procedure reported previously (5). A mixture of salicyaldehyde (0.5 mol)
and ethyl acetoacetate (0.5 mol) was stirred and cooled. To this mixture 10 g
of piperidine was added with shaking. The mixture was maintained at freezing temperature
for 2-3 hours resulting in a yellow colored solid mass, which was separated out.
It was recrystallized from ethanol to get the target compound. 79
Figure 6: Synthesis
of 3 – Acetyl coumarin by Knoevenagel reaction
1.25 Properties of 3AC
3: Properties of 3AC
120 – 1220 C
Solubility in water
Uses of 3 Acetyl Coumarin
3 Acetyl Coumarin is important initial compoundfor the synthesis of
coumarin and their derivatives has attracted considerable attention from
organic and medicinal chemists .
Applications of 3
v 3 Acetyl Coumarin application ranges from additive
in food, perfumes, cosmetics, pharmaceuticals.
v In the preparation of insecticides 80
v As optical brightners 80
v As dispersed fluorescent and tunable laser dyes 80
v Coumarin have varied bioactive for example
inhibition of platelet aggregation 80
v As anticancer 81
v Inhibition of steroid 5? – reductase 82
A polymer is defined as a macromolecule formed by
the repeated combination of several simple molecules (Monomers) through
Poly vinylpyrrolidone (PVP)
Poly vinylpyrrolidone (PVP), also
commonly called polyvidone or povidone, is a polymer made from the monomer
vinylpyrrolidone. It is also called briefly PVP, is one of the numerous
products 83.84 of the acetylene chemistry
founded by Reppe.
Preparation of PVP
By the reaction of acetylene with
formaldehyde, 1,4 – butenediol is obtained which is hydrogenated to butanediol.
After oxidative cyclization to butyroacteone and its reaction with ammonia, pyrrolidone is formed by the
removal of water. Finally the vinyl group is introduced to form N-Vinyl
pyyrrolidone-2(1-(2-oxo-pyrrolidinyl)-ethylene). The polymerization of
vinylpyrrolidone produces the polymeric material (fig. ). Vinylpyrrolidone can
polymerized either in bulk, in solution or in suspension.
Figure 7: Synthesis of
N-vinyl pyrrolidone from acetylene and formaldehyde
Polymerization of vinyl pyrrolidone
Properties of PVP
is a nonionic water-soluble polymer and can be applied in a variety of
fields-of-use owing to following advantageous characteristics
solubility in water as well as various organic solvents
affinity to various polymers and resins
film formation property
adhesiveness to various substrates
chelate / complex formation property
Application of PVP
A survey of most important application
of VP polymers is reported below