Physical properties of drug molecules
1 Physical state
Drug molecules exist in various physical states, e.g. amorphous solid,
crystalline solid, hygroscopic solid, liquid or gas. The physical state of
drug molecules is an important factor in the formulation and delivery of
drugs.
2 Melting point and boiling point
The melting point (m.p.) is the temperature at which a solid becomes a
liquid, and the boiling point (b.p.) is the temperature at which the vapour
pressure of the liquid is equal to the atmospheric pressure. The boiling point
of a substance can also be defined as the temperature at which it can change
its state from a liquid to a gas throughout the bulk of the liquid at a given
pressure. For example, the melting point of water at 1 atmosphere of
pressure is 0 C (32 F, 273.15 K; this is also known as the ice point) and
the boiling point of water is 100 C.
Melting point is used to characterize organic compounds and to
confirm the purity. The melting point of a pure compound is always
higher than the melting point of that compound mixed with a small
amount of an impurity. The more impurity is present, the lower the
melting point. Finally, a minimum melting point is reached. The mixing
ratio that results in the lowest possible melting point is known as the
eutectic point.
The melting point increases as the molecular weight increases, and the
boiling point increases as the molecular size increases. The increase in
melting point is less regular than the increase in boiling point, because
packing influences the melting point of a compound.
Packing of the solid is a property that determines how well the
individual molecules in a solid fit together in a crystal lattice. The tighter
the crystal lattice, the more energy is required to break it, and eventually
melt the compound. Alkanes with an odd number of carbon atoms pack
less tightly, which decreases their melting points. Thus, alkanes with an
even number of carbon atoms have higher melting points than the alkanes
with an odd number of carbon atoms. In contrast, between two alkanes
having same molecular weights, the more highly branched alkane has a
lower boiling point.
CH CH3CH2CH2CH2CH3 3CH2CH2CH3
CH3CH2CH2CH2CH2CH3
CH3CHCH2CH3
CH3 CH3CCH3
CH3
CH3
Pentane
m.p. = -129.7 oC
b.p. = 36.1 oC
Butane
m.p. = -138.4 oC
Hexane
m.p. = -93.5 oC
Isopentane
b.p. = 27.9 oC Neopentane
b.p. = 9.5 oC
3 Polarity and solubility
Polarity is a physical property of a compound, which relates other physical
properties, e.g. melting and boiling points, solubility and intermolecular
interactions between molecules. Generally, there is a direct correlation
between the polarity of a molecule and the number and types of polar or
nonpolar covalent bond that are present. In a few cases, a molecule having
polar bonds, but in a symmetrical arrangement, may give rise to a nonpolar
molecule, e.g. carbon dioxide (CO2).
The term bond polarity is used to describe the sharing of electrons
between atoms. In a nonpolar covalent bond, the electrons are shared
equally between two atoms. A polar covalent bond is one in which oneatom has a greater attraction for the electrons than the other atom. When this
relative attraction is strong, the bond is an ionic bond.
The polarity in a bond arises from the different electronegativities of the
two atoms that take part in the bond formation. The greater the difference
in electronegativity between the bonded atoms, the greater is the polarity
of the bond. For example, water is a polar molecule, whereas cyclohexane
is nonpolar. The bond polarity and electronegativity are discussed in
Solubility is the amount of a solute that can be dissolved in a specific solvent
under given conditions. The dissolved substance is called the solute and the
dissolving fluid is called the solvent, which together form a solution. The
process of dissolving is called solvation, or hydration when the solvent is
water. In fact, the interaction between a dissolved species and the molecules
of a solvent is solvation.
The solubility of molecules can be explained on the basis of the polarity
of molecules. Polar, e.g. water, and nonpolar, e.g. benzene, solvents do not
mix. In general, like dissolves like; i.e., materials with similar polarity are
soluble in each other. A polar solvent, e.g. water, has partial charges that can
interact with the partial charges on a polar compound, e.g. sodium chloride
(NaCl). As nonpolar compounds have no net charge, polar solvents are not
attracted to them. Alkanes are nonpolar molecules, and are insoluble in
polar solvent, e.g. water, and soluble in nonpolar solvent, e.g. petroleum
ether. The hydrogen bonding and other nonbonding interactions between
molecules are described in Chapter 2.
A solution at equilibrium that cannot hold any more solute is called a
saturated solution. The equilibrium of a solution depends mainly on
temperature. The maximum equilibrium amount of solute that can
usually dissolve per amount of solvent is the solubility of that solute in
that solvent. It is generally expressed as the maximum concentration
of a saturated solution. The solubility of one substance dissolving
in another is determined by the intermolecular forces between the solvent
and solute, temperature, the entropy change that accompanies the solvation,
the presence and amount of other substances and sometimes pressure
or partial pressure of a solute gas. The rate of solution is a measure of
how fast a solute dissolves in a solvent, and it depends on size of
the particle, stirring, temperature and the amount of solid already
dissolved.
4 Acid–base properties and pH
One of the adverse effects of aspirin is stomach bleeding, which is partly
due to its acidic nature. In the stomach, aspirin is hydrolysed to salicylic
acid. The carboxylic acid group (COOH) and a phenolic hydroxyl group
(OH) present in salicylic acid make this molecule acidic. Thus, intake of
aspirin increases the acidity of the stomach significantly, and if this
increased acidic condition remains in the stomach for a long period, it
may cause stomach bleeding. Like aspirin, there are a number of drug
molecules that are acidic in nature. Similarly, there are basic and neutral
drugs as well. Now, let us see what these terms acid, base and neutral
compounds really mean, and how these parameters are measured.
----------------------------------->
Hydrolysis in the stomach
Simply, an electron-deficient species that accepts an electron pair is called
an acid, e.g. hydrochloric acid (HCl), and a species with electrons to donate
is a base, e.g. sodium hydroxide (NaOH). A neutral species does not do
either of these. Most organic reactions are either acid–base reactions or
involve catalysis by an acid or base at some point.
Arrhenius acids and bases
According to Arrhenius’s definition, an acid is a substance that
produces hydronium ion (H3Oþ), and a base produces hydroxide ion
(OH) in aqueous solution. An acid reacts with a base to produce salt and
water.
HCl (Acid) + NaOH (Base))====>NaCl (Salt) + H2O (Water)
Brønsted–Lowry acids and bases
The Danish chemist Johannes Brønsted and the English chemist Thomas
Lowry defined an acid as a proton (Hþ) donor, and a base as a proton (Hþ)
acceptor.
HNO2 (Acid)+H2O(Base))===>NO2 (Conjugate base)+ H3O+ (Conjugate acid)
No comments:
Post a Comment