SURFACE ACTIVITY surfactant reduces surface tension of water at lower concentration.

Surface agent may enhance or retard the drug absorption,which depends upon the chemical nature of surfactant, it's concentration, it's effect on biological membrane,and micelle formation. At lower concentrations, the surfactant enhances the concentrations reduce the absorption rate absorption rate; the same in higher

In lower concentrations,they reduce the surface tension and bring about better absorption through better contact of the molecules With absorbing membrane, but when the concentration crosses the critical micelle concentration, the surfactant aligns them at the surface so that the hydrophilic end is towards the water and hydrophobic is squeezed away from the water.These molecular aggregates are called micelle, which entrap the drug molecule In their hydrophobic core, and result in the retardation of the rate of absorption The orientation of surface active molecules at the surface of water or at the interface of polar and nonpolar liquids takes place with nonpolar(hydrocarbon) portion of the molecule oriented towards the nonpolar liquid or vapour phase and polar groups towards polar liquid. CLASSIFICATION anionic:ordinary soaps salts of bile acid salts of sulphate or phosphate esters of alcohol salts of sulphonic acid Cationic:high molecular weight aliphatic amines quaternary ammonium derivatives Nonionic:polyethylene ethers glycol esters of fatty acids Amphoteric APPLICATION compounds showing pronounced surface activity usually are unsuited for use in the animals.Such compounds are lost through their adsorption by proteins, and they also have an undesirable feature of disorganizing the cell membrane and producing haemolysis of red blood cell.In general, highly surface active agents are not used internally, but only topically, as skin disinfectants or sterilizers for sterilization of instruments. Nonionic surfactants are largely-employed in pharmaceutical preparation for oral (sometimes even parenteral) use as solubilizing agents of water insoluble or slightly soluble drugs. Many central nervous system depressant drugs, such as sedative-hypnotic, anticonvulsant, and central relaxant agents possess the general structure of nonionic surface-active compounds.

PROTEIN BINDING Binding of drugs by plasma protein is usually readily reversible,with most Drugs bound to proteins in the albumin fraction The drug protein complex is too large to pass through the renal glomerular membranes and therefore remains in the circulating blood thereby prolonging the duration of action Protein binding not only may prevent rapid excretion of the drug also It limits the amount of free drug available for metabolism and for interaction with specific receptor sites Protein binding may also limit access to certain body compartments Other drugs may exert an indirect biological effect by displacing active substances from protein binding The protein bound anticoagulants dicumarol and warfarin are displaced from protein by many other drugs including phenylbutazone clofibrate sulfonamides etc.This displacement of the anticoagulant potentiates their action by increasing the amount of free drug available for competitive inhibition of vitamin k in the clotting process.The resulting increase in clotting time may lead to hemorrhaging Tissue protein or related tissue constituents may also bind drugs thus providing depots outside of the plasma

BIOISOSTERISM 1. In. SAR studies and drug design it is always necessary to compare the formal and three dimensional structure with the substituent and functional groups of compounds that show a similar spectrum of biological activities. In most instances. one may find similarities in molecular shape and overall chemical functions and Will base one's explanation of biological similarities on these resemblances. This total complex of analogies that comprises steric, electronic and molecular-orbital comparison is called bio-isosterism.

2.The parameters being changed are molecular size, steric shape, bond angles, hybridisation electron distribution, lipid solubility, water solubility, pKa, the chemical reactivity to cell components and metabolising enzymes and the capacity to undergo H-bonding (receptor interactions) 3.Bioisoters are (functional ) groups or molecules that have chemical and physical similarities producing broadly similar biological properties.

4.In order to develop new drug the structure of drug is considered to consists of two parts Critical or essential Noncritical or nonessential:allows sufficient changes without a considerable change in biological activity Various molecular modifications done on this noncritical part are classified as follows a)selectophores:Those modifications which confirm selectivity in action of the drug by regulating drug distribution b)contactophores:The modifications which by increasing penetration help the drug to reach the receptor site c)carrier moieties or conducting moieties:These moieties increase affinity of a drug Thus noncritical part is involved in passive transport of the drug While any change or modification of critical part of the drug molecule will result in the change of its biological activity,only those groups having similar steric,electronic and solubility characteristics can be interchanged.The study of such groups (bioisosters ) and their application in medicinal chemistry is known as Bioisosterism 5.CLASSIFICATION of bioisosters Classical:have similarities in shape and electronic configuration of atoms groups and molecules which they replace. a)monovalent atoms and groups E.g. CH2 NH2 OH and SH b)Divalent atoms and groups E.g. R-O-R', R-NH-R', R-CH2-R' and R-Si-R' c)Trivalent atoms and groups E.g. R-N=R' , R-CH=R' d)tetrasubstituted atom E.g. =C=, =N+=and =P+= e)Ring equivalents E.g. -CH = CH- , -S-, -O-, -NH and -CH2-

2.Nonclassical:do not rigidly fit the steric and electronic rules of classic bioisosters a)exchangeable group b)ring versus non cyclic structure 6.APPLICATION