PHYSICAL AND CHEMICALPROPERTIES OF DRUG MOLECULES 1

Introduction: Definition: To study the displined preparation of drug product or substance how to effect the body ,like Distribution, Metabolisom,Elemenation by involving Physical and Chemical parameters. Physical and chemical properties can be influence the process of drug transported from site of administration to site of action. Drug can be produce some Biological response in the body . It can be Produce response by interaction with Receptor, Enzymes , Membranes. 1

Physical &chemical properties of drug molecules Classification: Physical &chemical properties of drug molecules Physical properties Chemical properties solubility Hydrogen bonding Molar Refractivity Partition coefficient Complexation Bio-isosterism

vander wall attraction: SOLUBILITY solubility can be depending up on natureof solute and solvents well as temperature and pH K solubility=K SOLUTION K SOLID vander wall attraction: they are weak inter molecular forces(0.5-1.0 cal/mole) Temperature dependent Dipole-dipole bonding: These forces occur when electronegative elements are attracted to carbon atom Stronger(1.0-10cal/mole) Ionic bonding: formation of Ionic bond is attraction of cathion& anions 1

PARTITION COEFFICIENT commonly occur in inorganic compounds Relatively strong(5kcal/mole) PARTITION COEFFICIENT Leaving the aqueous extra cellular fluid Passing through a lipid membranes 3. Entering other aqueous environment before reaching the receptor 1

Partition coefficient is influencing the transport and distribution One of the most widely used properties in QSAR studies it can be defined as equilibrium constant of drug concentration for molecules In two phase p( unionized mol)= [drug] lipid [drug] water P(ionised mole)= [drug] lipid [1-a] [drug] water 1

This can be used in packing of drug substances BULK PROPERTY Bulk property of the solid form such as crystalline polymorphism, particle size, powder flow properties and surface characteristics are likely to change during process development. This can be used in packing of drug substances 1

it can be divided into two types. Inter molecular hydrogen bonding The hydrogen bonding is a special type of dipole-dipole interaction between the hydrogen atom in a polar bond such as N-H,O-H,F-H and an electronegative atoms like O,N,F. eg: H : O: …………H :O: H H it can be divided into two types. Inter molecular hydrogen bonding intra molecular hydrogen bonding 1

a) Inter molecular hydrogen bonding: hydrogen bonding occurs between two or more then molecules of the same or different compounds. Intermolecular hydrogen bonding increases the boiling point of the Compound and also its solubility in water. Dissociation More hydrogen bonding it have more energy required for evaporation or of the compound b) Intra molecular hydrogen bonding: hydrogen bonding occurs within two atoms of the same molecules. 1

This type of H-bond is commonly known as chelating of frequently occurs in Organic compounds Boiling point , solubility decreases because of formation of chelating. Chelating is not possible in the corresponding meta and Para position E.g.; o-nitrophenol MOLAR REFRACTION molar refraction is the molar volume corrected by refractive index it represent the size and polarizability of fragment or molecules 1

BIOISOSTERISM MR = n2-1 n2+1 * MW d A small MR for the same molecular weight indicates stronger interaction in the crystal. BIOISOSTERISM Langmuir introduced the term isosterism in 1919. 1

two molecules (of) ion (of) radical having the same number and arrangement of electrons are called isosterism ex: a) CO & NO2 b) CO2&N2O The wide spared application of concept of isosterism is to modify (or) improve biological activity that has been rise to the term BIO-ISOSTERISM . 1

Bio-isosteres are substitutes (or) groups that do not necessary have the same size (or) volume .but have a similar in chemical (or) physical properties It can be divided into two types 1) Classical bio-isoteres 2) Non-classical bio-isosteres 1

univalent atom Classical bio-isosteres: Classical replacement is “like for like “ in terms of number of atoms , valances, degree of unsaturation aromatic and then only becomes a bio-isosteric replacement if bio-logical activity is retained univalent atom a) -CH3,NH2 b) –CL, NH2 C)-Br,-I 1

non-classical bio-steres: Bivalent atom and group a) –CH2,-NH,-O b )COCH2 Trivalent, tetravalent atoms non-classical bio-steres: The non classical bio isosters comprise group which are structurally but do not meet the etectronic &steric requirement in rigorous 1

these isosters retain the activity by mimicking the spatial arrangement electronic properties (or) physico-chemical properties of molecules like pka COMPLEXATION Complexes (or) co-ordination of compound result from a donor acceptor mechanism or Lewis acid base reaction. Any non metallic atom whether free or contained in a neutral molecule can donate electron that is donor. 1

Pencillamine antidote for copper poisioning Compounds able to form ring with metal ion are called ligands Chelating property is restricted to only N, O,S which are electron donating. APPLICATIONS: Dimer caprol is chelating agent it is an effective antidote for arsenical lewsite & also used for antimony, gold& mercury poisoning Pencillamine antidote for copper poisioning 8-hydroxy quinoline -antibactericidal antifungal by complexing iron or copper 1

The ionisation of drug is dependent on its pka and the pH. IONIZATION OF DRUGS: The accumulation of ionised drug in acomportement of body is known as ion trapping The ionisation of drug is dependent on its pka and the pH. Handerson –hassclbatch relation ship gives us ratio of ionised or non ionised drug Non-ionize substances dissolved in lipid membrane and transported by passive deffusion 1

Ionized drug penetrated slow IMPORTANCE: The lower the pH relative to the pKa greater fraction of potentate drug Weak acid at acid ph more lipid soluble bcoz it is un charged, the uncharged form more readily pass through the biological membrane Weak base at alkaline PH also follows the same principle 1

it is the one of the factor for chemical properties Compatibility: it is the one of the factor for chemical properties In can be widely used in preformulation of drugs the activity ingredient is reacted with preservatives, coloring agent ,other substrates This properties over come prepare a stable drug 1

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