States of Matter PHM 312

What are the three states of matter discussed in the presentation?

Gases, Liquids, and Solids.

What are two specific examples of drugs that exist as gases?

Halothane and nitrous oxide (both used as anesthetics).

Why is the study of gases (like Boyle’s Law and Charles’ Law) useful in pharmacy?

It is useful in the design of aerosol dosage forms (with various applications like allergies, asthma, and smoking addiction).

What two physical factors control the physical state of a substance?

Temperature (measured in °C or °K) and pressure (measured in torr, mm Hg, atmospheres, etc.).

What generally happens to a gas as the temperature decreases or the pressure increases?

The gas becomes a liquid. (For many substances, but not all, further decreases in temperature and increases in pressure convert liquids to solids).

What is the critical temperature (Tc)?

The specific temperature above which a gas cannot be converted to a liquid, no matter how much pressure is applied.

Why is a gas unable to liquefy above its critical temperature?

Because the molecules are moving too fast due to high kinetic energy (increased molecular velocity).

What is critical pressure (Pc)?

The applied pressure required to liquefy a gas at its critical temperature.

What is the critical temperature (Tc) of Helium?

-268 °C.

What is the critical temperature (Tc) of Methane?

-82 °C.

What is the critical temperature (Tc) of Carbon Dioxide?

31 °C.

What is the critical temperature (Tc) of Ammonia?

133 °C.

What is the critical temperature (Tc) of Water?

374 °C.

Why does water have such a high critical temperature (374°C)?

Because it has very strong intermolecular attractions (specifically, hydrogen bonds).

Why is Helium extremely difficult to liquefy even at very low temperatures?

Because it has extremely weak interparticle forces.

What does an aerosol delivery system consist of?

A drug dissolved or suspended in an inert propellant.

What is the nature of the propellant used in aerosols at ordinary temperatures and pressures?

It is a gas or a volatile liquid.

How is the propellant forced into an aerosol container?

It is forced in at high pressures and low temperatures, which converts it to a liquid.

What happens when the pressure is released by operating the valve on an aerosol can?

The propellant is converted, in part, to the gas state and is expelled along with some of the drug.

What is vapor pressure?

The pressure exerted on the surface of a liquid by the molecules that escape into the vapor or gas state.

Why does vapor pressure increase as temperature increases?

The higher the temperature, the faster the molecules move, meaning more of them have enough energy to "escape" from the liquid and enter the vapor state.

What happens to vapor molecules if the container is open?

As molecules in the vapor state diffuse away from the surface, they must be replaced by other molecules from the liquid state, resulting in "evaporation."

Does evaporation take place in a closed or sealed container?

No, evaporation does not take place because the vapor cannot diffuse away.

In a closed container, what is the relationship between molecules in the vapor state and those in the liquid state?

There is an equilibrium relationship; the rates at which molecules move from one state to another are equal (Liquid ⇌ Vapor).

At what temperature does a liquid reach its boiling point regarding vapor pressure?

When the vapor pressure equals one atmosphere (760 mm Hg, 30 inches Hg).

What is the normal boiling point?

The boiling point of a liquid at a pressure of 1 atmosphere (e.g., 100°C for water, 80°C for benzene).

What happens to the temperature of a liquid as it is heated before it reaches the boiling point?

The temperature rises as heat goes into kinetic energy.

What happens to the temperature of a liquid when it reaches its boiling point?

The temperature remains constant until the liquid state is completely changed to the vapor state.

What is the heat of vaporization (ΔHv)?

The energy required to break intermolecular attractions and allow the liquid state molecules to completely enter the vapor condition.

What happens to the temperature after a liquid has completely changed into a vapor?

Continued heating will cause the temperature (of the vapor molecules) to rise again.

How do strong intermolecular attractions affect boiling point and heat of vaporization?

Substances with large intermolecular attractions have higher boiling points and greater heats of vaporization.

How do strong intermolecular attractions affect vapor pressure?

Substances with greater attractions have lower vapor pressures at any given temperature.

What is the boiling point of water and its ΔHv (in kcal/mole)?

B.P. is 100 °C; ΔHv is 9.7 kcal/mole.

What is the boiling point of ethanol and its ΔHv (in kcal/mole)?

B.P. is 78 °C; ΔHv is 9.4 kcal/mole.

What is the boiling point of ethyl ether and its ΔHv (in kcal/mole)?

B.P. is 35 °C; ΔHv is 6.7 kcal/mole.

What is the boiling point of chloromethane and its ΔHv (in kcal/mole)?

B.P. is -24 °C; ΔHv is 5.1 kcal/mole.

What is the boiling point of propane and its ΔHv (in kcal/mole)?

B.P. is -42 °C; ΔHv is 4.5 kcal/mole.

What is the boiling point of nitrogen and its ΔHv (in kcal/mole)?

B.P. is -196 °C; ΔHv is 1.3 kcal/mole.

What is the boiling point of helium and its ΔHv (in kcal/mole)?

B.P. is -269 °C; ΔHv is 0.024 kcal/mole.

Why does water boil at a lower temperature in Denver compared to Brooklyn?

The atmospheric pressure is lower in Denver (<1 atm), so a lower temperature is required for the vapor pressure to equal the atmospheric pressure.

Why does water boil at a higher temperature in Death Valley compared to Brooklyn?

The atmospheric pressure is higher in Death Valley (>1 atm), so a higher temperature is required.

What is the basis of vacuum distillation?

If a substance has a very high boiling point, it can be placed under low pressure (using a vacuum pump) so it boils (distills) more easily at a lower temperature.

What is the basis of a pressure cooker?

Increasing the pressure so that water boils at a temperature much greater than 100°C, allowing food to be heated to a higher temperature.

On a vapor pressure curve, what does any point to the left of the curve (lower temperature) represent?

The liquid state.

On a vapor pressure curve, what does any point to the right (higher temperature) represent?

The vapor state.

On a vapor pressure curve, what does any point on the curve represent?

A "boiling point," where interconversion of both liquid and vapor states occurs.

What does the Clausius-Clapeyron equation describe?

The relationship between vapor pressure and temperature, specifically the exponential increase in vapor pressure with increasing temperature.

What is the formula for the Clausius-Clapeyron equation (differential form)?

dp/dT = pΔHv / RT² (where p is vapor pressure, T is temperature in Kelvin, ΔHv is molar heat of vaporization, and R is the gas constant).

In the Clausius-Clapeyron equation, what is the value of R when calories are used?

R = 2 calories/degree-mole.

How many joules are in one calorie?

4.18 joules.

How many liter-atmospheres are in one calorie?

0.0413 liter-atmospheres.

How many ergs are in one calorie?

4.18 x 10⁷ ergs.

How many kilocalories are in one calorie?

1 x 10⁻³ kilocalories.

If the heat of vaporization is given in calories per gram, what must you know to convert it to cal/mole?

You must know the molecular weight of the substance.

How do you calculate the molar heat of vaporization for water if it is 540 cal/gram and the molecular weight is 18 g/mole?

540 cal/gram x 18 g/mole = 9720 cal/mole (or 9.72 kcal/mole).

What are some precautions when using the Clausius-Clapeyron equation?

Units must be consistent (ΔHv in calories, T in °K); the log of p1 must be added to the term on the right; the units of p2 will be the same as p1 (convert afterward if needed); T1 must be subtracted from T2 in the numerator.

How many mm Hg are in 1 atmosphere?

760 mm Hg.

How many torr are in 1 atmosphere?

760 torr.

How many inches of Hg are in 1 atmosphere?

29.9 inches Hg.

How many dynes/cm² are in 1 atmosphere?

1.01 x 10⁶ dynes/cm².

How many Newtons/m² (Pascals) are in 1 atmosphere?

1.01 x 10⁵ Newtons/m² (or Pascals).

How many kilopascals are in 1 atmosphere?

101 kilopascals.

Why is the solid state the most important physical state in pharmacy?

Most drugs are formulated as solids (tablets, capsules, powders, and suspensions), and their physical properties affect formulation, manufacture, and disposition in vivo.

How are molecules (or ions/atoms) arranged in a solid compared to a gas?

In solids, like liquids and unlike gases, the molecules are relatively close together.

How are molecules arranged in a solid compared to a liquid?

Unlike liquids, most solids have a definite pattern or shape (a crystal lattice).

What is polymorphism?

When a single substance can have a variety of crystal shapes/crystalline arrangements.

What is a crystal lattice?

The definite pattern or shape in which the various particles (molecules, ions, etc.) are arranged in a solid.

What holds a crystal together?

Lattice forces, which can be covalent bonds, ionic interactions, hydrogen bonds, or Van der Waal's forces.

How do strong lattice forces affect a crystal's properties?

They make the structure more stable, resulting in higher melting points and higher heats of fusion.

What is the heat of fusion (ΔHf)?

The energy required to convert the solid state to the liquid state (analogous to the heat of vaporization).

What is the relationship between the melting point and freezing point of a substance?

They are the same temperature.

For silicon, what is the bonding type, ΔHf (calories/mole), and melting point?

Bonding: covalent; ΔHf: 9500 cal/mole; Melting point: 1427 °C.

For NaCl, what is the bonding type, ΔHf (calories/mole), and melting point?

Bonding: ionic; ΔHf: >7000 cal/mole; Melting point: 800 °C.

For water, what is the bonding type, ΔHf (calories/mole), and melting point?

Bonding: hydrogen; ΔHf: 1440 cal/mole; Melting point: 0 °C.

For methane, what is the bonding type, ΔHf (calories/mole), and melting point?

Bonding: induced dipole (London/Van der Waal's forces); ΔHf: 226 cal/mole; Melting point: -183 °C.

What are induced dipole bonds (London or Van der Waal's forces)?

Forces that occur when a dipole (charge separation) is induced in a normally non-polar molecule (like CH4), causing the newly formed dipoles to weakly attract each other.

What is solubility?

The amount of compound that dissolves in a given volume of liquid (water being of most interest in pharmacy).

Why is solubility important for a tablet or capsule?

If the drug doesn't dissolve in the GI tract (which is largely aqueous), it will not be absorbed into the patient’s bloodstream.

Why are substances with strong lattice forces generally difficult to dissolve?

The lattice forces must be overcome before the solute and solvent can interact to form a solution.

Why is NaCl (which has strong lattice forces) still very soluble in water?

Because the attraction of the ions to the polar water molecules is also very strong.

Why are hydrocarbons (which have weak intermolecular forces) poorly soluble in water?

Because the interaction between these "non-polar" molecules and water is very meager.

What are some examples of drugs that exhibit polymorphism?

Chloramphenicol, haloperidol, tamoxiphen, carbamazepine, cortisone and other steroids, and aspirin.

Why do different polymorphs of the same drug matter in pharmacy?

Although chemically and pharmacologically the same, they can have different physical properties (like solubility), which can lead to differences in bioavailability (the amount of drug that gets into the bloodstream and the rate).

When choosing a polymorph of a drug for a dosage form, which one should generally be chosen?

The one with the best solubility, even if it is not the most stable form.

What is an amorphous form of a substance?

A form that has essentially no "true" crystalline shape.

Why is the amorphous form often the most desirable form to use for a drug?

Because there is essentially no lattice structure to break down, the energy required to dissolve the substance is minimal, leading to enhanced solubility.

What can happen if a crystalline form of a drug is used instead of an amorphous form?

It may produce far smaller blood levels and slower absorption rates (less bioavailability).

What happens to the temperature of a solid as it is heated before it reaches the melting point?

The temperature increases as added heat is used to increase kinetic energy.

What happens to the temperature of a solid when it reaches the melting point?

It remains constant (for pure substances) until the solid completely melts.

What is a supercooled liquid?

A liquid that exists below its melting (freezing) point because it takes time for the molecules or atoms to set up in their unique crystalline pattern.

What is an example of a supercooled liquid that never gets back to the true solid state?

Glass (after melting and cooling silicon dioxide/sand). Large organic molecules like fats, waxes, and polymers can also do this.

Are supercooled liquids considered crystalline or amorphous?

They are essentially amorphous solids since they have no real crystalline shape.

On a phase diagram, what does the solid-liquid line (OA) represent?

The equilibrium between solid and liquid phases. To the left only solid exists; to the right only liquid exists.

On a phase diagram, what does the liquid-vapor line (OB) represent?

The equilibrium between liquid and vapor phases (the vapor pressure curve). To the left only liquid exists; to the right only vapor exists.

On a phase diagram, what does the solid-vapor line (OC) represent?

The equilibrium between solid and vapor phases. Above only solid exists; below only vapor exists.

What is sublimation?

The conversion of a solid directly to a vapor (the reverse is condensation).

What is the triple point on a phase diagram?

The only pressure and temperature at which all three phases (solid, liquid, and vapor) are in equilibrium (where the three lines converge).

For most compounds on a phase diagram, what happens to the melting point as pressure increases?

The conversion temperature of solid to liquid increases as pressure increases (the solid-liquid line slopes up and to the right).

Why is water an anomalous compound on a phase diagram?

Water melts at a lower temperature as pressure increases because the density of the solid (ice) is less than that of the liquid (water).

Why does ice float and water expand when it freezes?

Because water is anomalous and the density of the solid form is less than the density of the liquid form.