Vapor Pressure and States of Matter

relationship between IMF and VP

the stronger the intermolecular

forces, the lower the number of molecules that can escape the liquid state, the lower the vapor pressure.

Boiling point (BP):

is defined as the temperature at which the VP of a liquid equals the atmospheric pressure.

➢ Obviously, VP and BP are related to the intermolecular forces. Tightly bound molecules will be less likely to

evaporate and the liquid will have low vapor pressure and vice versa

by comparing its vapor pressure (VP) and/or

boiling point (BP) to those of water

highly volatile liquids have high vapor pressure

but low boiling points.

To summarize then and the general rules we will go by in solving problems:

 Non-polar molecules have lower BP than polar molecules because non-polar molecules are held together

by the weak induced dipole-induced dipole forces.

 Polar molecules have high BP because the molecules associate by the strong polar interactions such as H-

bonding.

 The higher the molecular weight the stronger the van der Waal interactions and the higher BP

 Branching of molecules weakens their associations and, hence, lowers the BP

 Also, (MEMORIZE) the higher the BP the lower the VP at room temp.

 MEMORIZE those rules so you can rank a group of given structures according to properties like VP and BP.

solids

solid drugs are only absorbed from solution form.

 This means that for any solid drug to be absorbed into circulation and produce pharmacological effects it has

to dissolve in body fluids (which are basically aqueous) first.

Molecules of a solid in the amorphous form are not arranged in any specific geometric pattern. Because of

this, the polar groups are exposed and accessible to water, which speeds up the dissolution process. More

soluble means more readily absorbed and, hence, more biologically active. So, the rule to memorize here

is:

the amorphous form of solid drugs are more biologically active.

the molecules of a solid in the crystalline form are tightly bound to each other and pack

in highly ordered fashion which masks the polar groups and make them inaccessible to water molecules.

Consequently, the crystalline form of a solid drug is less soluble and, hence, poorly absorbed and less

biologically active than the amorphous form. The second part to the rule above, therefore, is:

the

crystalline form of a solid drug, is inactive or less biologically active than its amorphous form.

How do we know if the solid we have is crystalline or amorphous?

From the melting behavior as follows:

 Melting is when the solid turns into liquid and the temperature at which this transition occurs is called the

melting point (MP).

 Let us compare the melting behavior of an icicle (a crystalline solid) and a plastic pen (plastic is an

amorphous solid). If you heat an icicle, it melts immediately and the melting occurs over a very narrow

and well-defined temperature range. But if you heat the plastic pen, it softens (does not completely turn

into liquid) over a broad range of temperatures.

 In conclusion then, to determine whether we have the crystalline or the amorphous form of a solid,

determine its melting point and monitor the melting behavior.

do solid drugs have only one crystal form? Or can there be more than one? and If there are

more than one, are they all equally biologically active?

Molecules of a solid can arrange in many different patterns depending on the size and shape of the

molecule, the functional groups it has and on the crystallization conditions. A solid drug, therefore, can

crystalize in more than one crystal form. The different crystal forms of a solid drug may or may not be

equally biologically active because each crystal has different aqueous solubility.

When the molecules of the same compound arrange in more than one crystal form, this phenomenon is

known as polymorphism; and the molecule is described as a polymorphic one.

A polymorphic pharmaceutical is, by definition, a solid ingredient that crystallizes in

more than one crystal form depending on the crystallization conditions.

Polymorphism is a serious problem in the pharmaceutical industry because

the different crystal forms of the

same active ingredient may have different aqueous solubilities which leads to varied biological response.

An important question, then, is how can we identify what crystal form we have?

using the

melting point (MP) test.

The most stable crystal form,

which is the one with the strongest intermolecular forces between

molecules, has the highest MP among all other crystal forms of the drug.

 We should, therefore, be able to correlate intermolecular forces and MPs.

 The general rules we will go by here are:

 Changes in the state of matter depends on the nature of forces holding the molecules together

 With regards to evaporation (i.e. going from the liquid state to the gas one): the stronger the intermolecular

forces the higher the BP but the lower the VP

 With regards to melting (i.e. going from the solid state to the liquid one): the higher the intermolecular

forces the MP.

Phase equilibria and phase diagrams

It is important to know that all pharmaceutical products should exist as a homogenous one phase system

to ensure equal distribution of active ingredients in all parts of the product to ensure consistent dosing.