1.21 Formation of ternary complexesWhena water soluble polymer and CD and a drug mixed together in a solution toobtain the so called ternary complexes, it is possible increase to drugsolubilization, when compared to the polymer and CD separately, which is aresult of the synergistic effect between the components. Formulationscontaining drug: CD complexes with the addition of a water soluble polymer haveproven to be capable of increasing the bioavailability of formulations whilereducing the amount of CD by up to 80% 73. In the presence of water, the polymer aids in the wettability ofparticles resulting in the accelerated dissolution and increased amount of drugdelivered in vitro 74.Theinteraction of water – soluble polymers with drug may occur by means of ion –ion, ion – dipole, dipole – dipole electrostatic bonds, Vander Waals force, or3 –center, 2 – electron bonds 75. Similarly the interaction between polymers and CDs and drug: CDcomplexes begins to occur on the external surface of the CD molecule. CDspolymers and drug: CD complexes form aggregates capable of solubilizing drugsand other hydrophobic molecules 76, as shown in figure.
Figure 4: Representation ofternary complex formation between drugs, CD and water soluble polymer 1.22 3 – Acetyl Coumarin ( 3AC)Coumarins and their derivatives form an elite classof compounds, occupying an important place in the realm of natural products andsynthetic organic chemistry 77.3-acetyl-coumarins are important initial compounds for the synthesis ofcoumarins and the synthesis of coumarins and their derivatives has attractedconsiderable attention from organic and medicinal chemists for many years as alarge number of natural products contain this heterocyclic nucleus. Coumarin (benzopyrones or 2-oxo-2H-chromene) is a compound containing two structures ofsix member heterocyclic rings with two oxygen atoms. Classification ofcoumarins includes simple coumarin, furanocoumarins, pyranocoumarins and coumarins substituted inthe pyrone ring 78.
Simple coumarins are compound that undergoes hydroxylation, alkoxylation andalkylation to form its derivatives. Coumarin can be found in several plantsnotably with high concentration in the tonka bean (Dipteryx odorata), vanillagrass (Anthoxanthum odoratum), woodruff (Galium odoratum), mullein (Verbascum spp.), and sweet grass (Hierochloe odorata). Ithas 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, stemand foliage and suitable solvents can be used in extraction for its isolation.
Coumarins also can be produced through organic synthesis although it can befound naturally in several green plants. The 3-Acetylcoumarin is also known as 2H-1-Benzopyran-2-one or 3-Acetyl-2H-chromen-2-one. 3-Acetylcoumarinexists in two polymorphic forms i.e. form A (Triclinic) andform B (Monoclinic).
1.23Structure of 3AC Molecular formula of. 3AC is C11H8O3. Figure5: Structure of 3-AcetylCoumarin 1.24 Synthesis of 3AC3-Acetylcoumarin was prepared accordingto 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 gof piperidine was added with shaking. The mixture was maintained at freezing temperaturefor 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: Synthesisof 3 – Acetyl coumarin by Knoevenagel reaction 1.25 Properties of 3AC Table 3: Properties of 3AC Molar mass 188.
1794 Appearance Pale Yellow Melting point 120 – 1220 C Solubility in water Sparingly soluble 1.26Uses of 3 Acetyl Coumarin3 Acetyl Coumarin is important initial compoundfor the synthesis ofcoumarin and their derivatives has attracted considerable attention fromorganic and medicinal chemists .1.
27Applications of 3Acetyl Coumarinv 3 Acetyl Coumarin application ranges from additivein food, perfumes, cosmetics, pharmaceuticals.v In the preparation of insecticides 80v As optical brightners 80v As dispersed fluorescent and tunable laser dyes 80v Coumarin have varied bioactive for exampleinhibition of platelet aggregation 80v As anticancer 81v Inhibition of steroid 5? – reductase 82 1.28PolymerA polymer is defined as a macromolecule formed bythe repeated combination of several simple molecules (Monomers) throughcovalent bonds.1.29Poly vinylpyrrolidone (PVP)Poly vinylpyrrolidone (PVP), alsocommonly called polyvidone or povidone, is a polymer made from the monomervinylpyrrolidone. It is also called briefly PVP, is one of the numerousproducts 83.
84 of the acetylene chemistryfounded by Reppe.1.30Preparation of PVPBy the reaction of acetylene withformaldehyde, 1,4 – butenediol is obtained which is hydrogenated to butanediol.After oxidative cyclization to butyroacteone and its reaction with ammonia, pyrrolidone is formed by theremoval of water. Finally the vinyl group is introduced to form N-Vinylpyyrrolidone-2(1-(2-oxo-pyrrolidinyl)-ethylene). The polymerization ofvinylpyrrolidone produces the polymeric material (fig.
). Vinylpyrrolidone canpolymerized either in bulk, in solution or in suspension. Figure 7: Synthesis ofN-vinyl pyrrolidone from acetylene and formaldehyde Figure 8:Polymerization of vinyl pyrrolidone 1.31Properties of PVP Structure: Colour: WhitepowderPVP-Polyvinylpyrrolidoneis a nonionic water-soluble polymer and can be applied in a variety offields-of-use owing to following advantageous characteristicsØ Goodsolubility in water as well as various organic solventsØ Goodaffinity to various polymers and resinsØ HighhygroscopicityØ Goodfilm formation propertyØ Goodadhesiveness to various substratesØ Goodchelate / complex formation property 1.32Application of PVPA survey of most important applicationof VP polymers is reported below