Chapter 3 Pharmaceutics

Front 1

What are the three different states of matter?

Back 1

Gases, liquids, and crystalline solids

Front 2

What influences the three states of matter?

Back 2

Temperature and pressure--these affect each state differently

Front 3

How do gas molecules move?

Back 3

They travel in a random path due to vigorous and rapid motion. They tend to collide with one another and the walls of their container.

Front 4

What kind of energy do gas molecules possess?

Back 4

Kinetic energy--therefore, gases exert pressure

Front 5

What are the units for pressure?

Back 5

force per unit area: dynes/cm^2

or mmHg

Front 6

How are gas molecules held together?

Back 6

By intermolecular forces

Front 7

What is the unit for volume?

Back 7

liters or cc (cubic centimeter)

Front 8

What do the various gas laws describe?

Back 8

The relationship between temperature (T) and pressure (P) and volume (V) of a gas.

Front 9

What are the names of the three gas laws?

Back 9

Boyle's Law, Charles' Law, and Gay Lussac Law

Front 10

What happens when a gas is cooled?

Back 10

It loses its kinetic energy in the form of heat and the velocity of molecules decreases

Front 11

What happens when gas molecules are

subjected to pressure?

Back 11

If they are brought within Van der Waal's interaction forces--they can pass into a liquid state.

Front 12

Give an example of a major application of gases in pharmaceutical science.

Back 12

The interpretation of blood gases in patients. The gases are dissolved in the blood on the basis of their solubility. (oxygen and carbon dioxide)

Front 13

Compare the density of liquids and gases.

Back 13

Liquids are more dense than gases.

Front 14

Describe liquids volume and how they take shape.

Back 14

They occupy a definite volume and take the shape of the container they are held in.

Front 15

Are liquids compressible?

Back 15

No

Front 16

How does the kinetic energy of liquids compare to that of gases?

Back 16

Liquids have less kinetic energy than gases.

Front 17

Describe the flow of liquid.

Back 17

Liquids flow very readily and it is influenced by friction.

Front 18

Liquids can become a solid by...

Back 18

freezing

Front 19

What is it called when a liquid becomes a gas?

Back 19

boiling point

Front 20

What dosage form does surface tension play a major role in?

Back 20

Liquid dosage forms, such as emulsions. These have an oil and water phase that is mixed

together to make a uniform liquid. It is done by incorporating surface active agents into the emulsion.

Front 21

What is vaporization?

Back 21

When liquid is converted into vapor.

Front 22

What is condensation?

Back 22

When vapor is converted into liquid.

Front 23

Describe equilibrium vapor pressure. (units)

Back 23

The pressure of the saturated vapor above the liquid. It tells you the rate of vaporization and

condensation has become equal to each other. Different temperatures have different

equilibrium vapor pressures and conditions. (mmHg)

Front 24

Describe how kinetic energy is distributed in a beaker of water.

Back 24

The kinetic energy is not evenly distributed. Each individual molecule has different kinetic energy. The molecules that have more kinetic energy have higher velocities.

Front 25

What happens to molecules with greater energy in a beaker of water?

Back 25

They breakaway from the surface of the liquid and pass into a gas state--some of the molecules return to the liquid state (condensation).

Front 26

What happens when dynamic equilibrium is

established?

Back 26

This means the rate of vaporization and condensation have become equal at a definite temperature--also the vapor has become saturated.

Front 27

Describe what happens to vapor pressure when the temperature rises.

Back 27

More molecules will approach the velocity

needed to escape and pass into the gas state. This means that vapor pressure will increase.

*lower temp=less vapor pressure

Front 28

Can different liquids have different vapor

pressure?

Back 28

Yes. In class, we were given a chart comparing

acetone, benzene, water, and acetic acid. They all have a different vapor pressure at each different temperature. It is related to heat of vaporization (unique to all liquids).

Front 29

What would happen to a liquid if temperature was increased and the pressure was kept

constant?

Back 29

All of the liquid would pass into the vapor state

Front 30

What would happen to a liquid if the pressure is decreased while the temperature is constant?

Back 30

All the liquid would pass into the vapor state.

Front 31

What relationship does the Clausius-Clapeyron equation express?

Back 31

The relationship between vapor pressure and absolute temperature (T) of a liquid. It allows us to find the heat of vaporization of a liquid.

Front 32

What is the Clausius-Clapeyron equation or

formula?

Back 32

P2 deltaHv (T2 - T1)

log ____ = ____________________

P1 2.303 R (T1 * T2)

Front 33

What does P and T stand for in the Clausius-Clapeyron equation?

Back 33

P is the vapor pressures at absolute temperatures, T.

Front 34

What is absolute temperature equal to?

Back 34

0 degrees C

or

273.16 Kelvin

Front 35

What does delta Hv stand for in the Clausius-Clapeyron equation?

Back 35

Molar heat of vaporization

Front 36

What is the molar heat of vaporization? (units)

Back 36

It is the heat absorbed by 1 mole of a liquid when it passes into the vapor phase (cal/gram, cal/mole)

Front 37

What does R stand for in the Clausius-Clapeyron equation?

Back 37

It is the molar gas constant and is equal to:

1.987 cal.mole^-1.deg^-1

0.08205 lit.atm.mole^-1.deg^-1

8.314 joules.mole^-1.deg^-1

Front 38

When does the heat of vaporization vary?

(2 answers)

Back 38

It varies with temperature.

It varies from chemical to chemical.

Front 39

Generally, the higher the heat of vaporization...

Back 39

the higher the boiling point

*Heat of vaporization tells you the magnitude of the attractive forces

Front 40

Define boiling point. (units)

Back 40

The temperature at which vapor pressure of a liquid equals the atmospheric pressure (degrees C, K, F)

*considered as the temperature at which thermal agitation can overcome the attractive forces between the molecules of a liquid

Front 41

All absorbed heat is utilized to convert the liquid into the vapor...meaning what will happen to the temperature?

Back 41

The temperature does not rise until the liquid is completely vaporized.

Front 42

What is the pressure at sea level in mmHg? What happens to boiling point when pressure is

decreased?

Back 42

sea level: 760 mmHg

Higher elevation=pressure decrease=lower

boiling point

Front 43

What is latent heat of vaporization?

Back 43

The heat absorbed when a liquid vaporizes at normal boiling point.

*It describes the quantity of heat taken up when a liquid vaporizes and is liberated when vapors condense into liquids.

Front 44

What three factors can provide a rough

indication of the magnitude of attractive forces in a liquid?

Back 44

*boiling point

*heat of vaporization

*vapor pressure

Front 45

When molecular weight increases, how is boiling point affected?

Back 45

The boiling point will increase with an increase in molecular weight--due to attractive forces becoming greater with an increasing number of carbon atoms (more compact arrangement)

Front 46

How much does boiling point increase in straight chain primary alcohols and carboxylic acids for each additional methylene group?

Back 46

18 degrees C

Front 47

Molecules of a liquid that are held together by London forces exhibit...

Back 47

low boiling points and low heat of vaporization

Front 48

What three things happen when a chain

branches in a liquid?

Back 48

*less compact molecule

*reduced intermolecular attraction

*decreased boiling point

Front 49

Describe crystalline solid shape and

arrangement.

Back 49

They have a definite shape and an orderly arrangement. (fixed geometric pattern or lattice) They have repetitious 3D units. There are 6 common crystalline structures

Front 50

Are solids compressible?

Back 50

No, they are practically incompressible.

Front 51

Describe crystalline solid melting point.

Back 51

They have a definite melting point, it passes sharply from solid to liquid state with a range of 1 to 2 degrees.

Front 52

Do solids have strong intermolecular forces?

How much kinetic energy do solids have?

Back 52

They have very strong intermolecular forces.

The have very little kinetic energy.

Front 53

What three factors are solids characterized by?

Back 53

*shape of crystal

*particle size

*melting point

Front 54

Can solids undergo sublimation?

Back 54

Very few solids are volatile enough to have a sublimation point, but iodine can. Sublimation is the change from solid to vapor state (no liquid phase).

Front 55

What is one way to detect the purity of a solid?

Back 55

Check the melting point. If the melting point doesn't match the known value, you know it is not a pure product.

Front 56

Solids can be classified into three different types. What are they?

Back 56

*crystalline

*amorphous

*polymeric

Front 57

Give an example of a cubic, tetragonal, and

orthorhombic crystalline solid.

Back 57

*cubic: sodium chloride

*tetragonal: urea

*orthorhombic: iodine

Front 58

Give an example of a monoclinic, triclinic, and hexagonal crystalline solid.

Back 58

*monoclinic: sucrose

*triclinic: boric acid

*hexagonal: iodoform

Front 59

The crystal structure can be made up of what three things?

Back 59

*atoms

*molecules

*ions

Front 60

How is the solid, sodium chloride, held together?

Back 60

By electrostatic attraction between oppositely charged ions--has a cubic lattice of sodium ions that are interpenetrated by a lattice of chloride ions.

Front 61

Diamond and graphite are held together by...

Back 61

covalent bonds which are very strong

Front 62

Inorganic compounds are held together by what two types of bonds?

Back 62

Van der Waal's forces and hydrogen bonding

*produces weak bonds and low melting point

Front 63

What are amorphous solids?

Back 63

They are non-crystalline powder material

Front 64

What kind of order and structure do amorphous solids have?

Back 64

There is no definite order or structure. It lacks a good, hard crystal structure and strong forces.

*causing them to be more soluble and more bioavailable than crystalline solids

Front 65

Why are amorphous solids referred to as super cooled liquids?

Back 65

Because of the random order of arrangement and distortion of the shape under pressure.

Front 66

Describe the melting point of amorphous solids.

Back 66

There is no definite melting point--the transition to a liquid state occurs over several degrees (5 to 6 degree range).

Front 67

Are crystalline or amorphous solids more

soluble and bioavailable?

Back 67

Amorphous solids are more soluble and bioavailable

*due to poor structure and weak forces

Front 68

Is it possible for pharmaceutical materials to exist in the solid state as both amorphous and crystalline?

Back 68

Yes--petrolatum, pork and human insulin, and some antibiotics (Novobiocin)

*crystalline dissolves slowly so it will have a longer onset of action--think of insulin

Front 69

What helpful information for the dosage form needs to be considered with solids?

Back 69

The first major distinction is whether it is

crystalline or amorphous.

Front 70

How does the amorphous solid compare to crystalline solids in thermodynamic energy?

Back 70

Amorphous form has higher thermodynamic

energy

*shown in the differences in solubility and

dissolution

Front 71

What happens to amorphous solids upon

storage?

Back 71

They revert to a more stable form--which is not a desired form.

*it can occur during bulk processing, within a dosage form, or during development of dosage forms

*can affect bioavailability

Front 72

Name 5 important properties of solids.

Back 72

*x-ray diffraction

*melting point

*equilibrium/saturation solubility

*polymorphism

*hydrated/anhydrous form

Front 73

Describe x-ray diffraction.

Back 73

X-rays are diffracted by crystals due to the x-rays having a wavelength (30 nm) of the same magnitude as the distance between atoms of a crystal.

Front 74

Regarding x-ray diffraction, each powder crystal has its own pattern which helps to...

Back 74

establish the identity and purification of a compound

Front 75

What two things does melting point help

establish in solids?

Back 75

*identity and purity

Front 76

Define melting point.

Back 76

It is the temperature at which a solid passes into a liquid state

or

the temperature at which pure liquid and solid exist in equilibrium

*taken at a pressure of 1 atm

Front 77

What is the latent heat of fusion? What is it's symbol? What are the units?

Back 77

The heat absorbed when a solid becomes a liquid and heat is liberated when liquid freezes (delta Hf)

*units: calories/gram

Front 78

What is the latent heat of fusion of water at 0C?

Back 78

It is about 80 calories/gram or 1436

calories/mole.

Front 79

Does the heat added during melting bring about change in temperature?

Back 79

No it does not--not until all of the solid has

disappeared or melted. Since the heat is being converted into the potential energy of the

molecules that have escaped from the solid to liquid state.

Front 80

What is the heat of fusion?

Back 80

The heat required to increase the intermolecular distances in the crystal to allow melting to occur.

Front 81

Describe the heat of fusion and melting point of crystals.

Back 81

If the bonds holding it together are weak, they are low.

If the bonds holding it together are strong, they are high.

Front 82

What is the relationship between aqueous

solubility and molecular weight?

Back 82

aqueous solubility decreases as molecular weight increases

Front 83

What is the relationship between aqueous

solubility and melting point?

Back 83

as solubility decreases, melting point increases

Front 84

What is equilibrium or saturation solubility?

Back 84

The maximum amount (mg or g) of a solute or drug that is present in a solution form per unit volume (ml or L) of a solvent at a constant temp and pressure.

Front 85

What is equilibrium condition?

Back 85

The condition when the rate of transfer of a solid in the solvent and the rate of deposition of solute molecules from the solvent on to the solid crystal become equal.

Front 86

What is the definition of solubility?

Back 86

The maximum amount (mg) of solute present in a solution form per unit volume (ml or L) of a

solvent at constant temp and pressure

--following the attainment of the equilibrium condition.

Front 87

What is the solubility of a substance?

Back 87

The quantity that will dissolve in a specified quantity of a solvent to form a saturated

solution at a given temp and pressure.

Front 88

What is a saturated solution?

Back 88

A solution in which drug molecules in the

solution are in equilibrium with an excess of solute in a solution.

Front 89

What is a super-saturated solution?

Back 89

A solution containing more of the dissolved solute than it would normally contain at a

definite temperature.

Front 90

What are two examples of salts that can be

dissolved in larger amounts at elevated

temperatures and not precipitate upon cooling?

Back 90

*sodium thiosulfate

*sodium acetate

Front 91

What are the 5 requirements for a compound to be most likely successful in becoming a drug?

Back 91

*BCS (biopharmaceutical classification system)

*equilibrium solubility

*partition coefficient

*permeability of a drug

*dissolution of a drug

*these physical-chemical properties allow us to predict if the drug will have bioavailability problems or not

Front 92

What is permeability?

Back 92

The ability of a drug molecule to pass through the lipophilic barriers--measured by permeability coefficient.

Front 93

Is griseofulvin soluble? What type of agent is it? What dosage forms is it available in?

Back 93

*poorly soluble

*antifungal agent

*tablet (grisPEG) and suspension dosage form

*PEG (polyethylene glycol) is added to reduce the particle size to make it in micronized form

Front 94

Are solubility expression precise? What do they tell us?

Back 94

They are not very precise.

They tell us the extent to which a drug is soluble in a solvent.

*USP, N.F., Remington

Front 95

Solubility can be expressed in a more precise manner. How so?

Back 95

It can be described as amount/unit volume.

For example, 1 gram of sodium chloride dissolves in 2.786mL of water. (35.89g/100mL)

Front 96

What are the 4 ways to express concentrations?

Back 96

*Molarity (molar solution)

*Normality (normal solution)

*Molality (molal solution)

*Mole fraction

Front 97

What is molarity?

Back 97

Moles/Liter of solution

Front 98

What is normality?

Back 98

Gram equivalent weight of solute/Liter of

solution

(1 normal=1 M)

Front 99

What is molality?

Back 99

Moles/1000 grams of solvent

Front 100

What are mole fractions?

Back 100

The ratio of moles of one constituent (solute) of a solution to the total moles of all constituents (solute and solvent).

Front 101

What must you know to calculate mole fractions?

Back 101

The molecular weight and the amount being used for the solvent and solute.

Front 102

What are the units of solubility and

concentration?

Back 102

They are the same. mg/liter or grams/liter or moles/liter

Front 103

Why is solubility important?

Back 103

*formulation of oral solution, IV injectable, and ophthalmic solution dosage forms depends on it

*can predict potential dissolution problems from solid dosage forms

*formulation of very hydrophobic drugs into solid forms can require incorporation of wetting agents and special manufacturing/equipment

*formulation of very hydrophobic drugs into suspension can require special excipients, manufacturing/equipment

Front 104

Hydrophobic compounds are likely to have problems with what? What can be done to help this?

Back 104

Dissolution. Surface active agents are necessary to reduce the tension between the powder

particles and liquid medium--the powder

material can then completely disperse into

liquid.

Front 105

For drug candidates with poor water solubility or insufficient solubility for a desired solution dosage form, pre-formulation studies should include...

Back 105

limited experiments to identify possible co-solvents and mechanisms for solubilization.

Front 106

Give an example of one way to increase

solubility of a drug.

Back 106

adding a water miscible co-solvent to the

aqueous system

Front 107

What are some examples of suitable co-solvents that can help improve solubility of poorly soluble non-electrolytes?

Back 107

*ethanol

*propylene glycol

*glycerin

*sorbitol

*polyethylene glycol (low molecular weight <400)

*biological buffers (ph 1-8)

Front 108

What is the pH of most oral liquids?

Back 108

3.5 to 5

Front 109

What are buffers?

Back 109

They are substances that resist a change in pH

Front 110

How can you determine the equilibrium

solubility of a drug?

Back 110

*In a glass container, place suitable solvent

*Continue to add small amounts of powder drug with continuous stirring/shaking at constant temp until no more drug dissolves

*Make sure that not all added powder drug is completely in solution

*know volume of samples of supernatant solution are taken out at suitable time intervals & analyzed by using analytical procedure to establish a plateau concentration

Front 111

What precautions need to be taken while performing solubility studies?

Back 111

*care in choosing a solvent--the improper solvent can enhance the degradation of the drug due to di-electrical constant

*components of buffers can also catalyze degradation of drugs

*pH, temp, ionic strength, buffer conc. should be defined clearly

Front 112

When performing equilibrium solubility determinations, what should be done with excess drug dispersed in a solvent?

Back 112

It should be agitated and kept at a constant

temperature.

Front 113

What is the relationship between solubility and temperature?

Back 113

The higher the melting point, the lower the

solubility

Front 114

True/False

If you lower the melting point, the solubility will be lower.

Back 114

False--the solubility will be higher.

Front 115

What excipients can solve flow problems?

Back 115

glident and lubricant

Front 116

What factors can influence aqueous solubility?

Back 116

*molecular size

*interaction of substituent groups with solvent

*availability of drug in different salts

*crystal property

Front 117

When will you have a drug in 50% ionized form and 50% unionized form?

Back 117

When the pH is equal to pKa.

Front 118

Are the majority of drugs weak acids, strong acids, weak bases, or strong bases? (pick 2)

Back 118

Weak acid or weak base

Front 119

What are some examples of weak acidic drugs?

Back 119

*barbiturates

*NSAIDS

*nitrofurantoin

*theophylline

*phenytoin

Front 120

What is the solubility of weak acidic drugs in acidic solution?

Back 120

They are less soluble in acidic solution.

Front 121

What is the solubility of weak acidic drugs in alkaline solution?

Back 121

They are more soluble in alkaline solution--this is due to the predominant unionized form that can't interact with water molecules to the same extent as ionized species which is readily hydrated.

Front 122

What happens to a drug in water when it is mainly in the ionized form?

Back 122

Water molecules can hydrate it readily and

dissolve it (good solubility)

Front 123

What is the symbol for a weak acid in an equation?

Back 123

HA

Front 124

What does S stand for in an equation?

Back 124

the total solubility of the drug

Front 125

What does S0 stand for in an equation?

Back 125

The solubility of an unionized species (HA)

Front 126

S = _______________________

Back 126

S0 + concentration of ionized

Front 127

The dissociation of a weak acid in water can be written by what equation?

Back 127

HA + H2O = H3O + A-

Front 128

The dissociation constant is Ka. What is it's equation?

Back 128

Ka = [H3O] [A] / [HA]

Front 129

How can you substitute S0 into the Ka equation?

Back 129

You replace [HA] with S0

Ka/[H3O] = [A-]/ S0

Front 130

What is [A-] equal to?

Back 130

[A-] = S - S0

Front 131

Substitute S - S0 into the Ka equation.

Back 131

Ka/[H3O] = S-S0 / S0

Front 132

From what equation do we know that the solubility of a weak acidic drug, at any pH, can be calculated when given the pKa and the solubility of the unionized?

Back 132

pH - pKa = log S-S0/S0

Front 133

How do you write the linear version of the solubility equation?

Back 133

log (S-S0) = pH + log Ka*S0

Front 134

In weak acidic drugs, when the solubility is low, the pH is...

Back 134

lower

Front 135

High [H+] means what for pH?

Back 135

It will be low.

Front 136

Low [H+] means what for pH?

Back 136

It will be high.

Front 137

For a weak acidic drug with a plot of log ( S - S0 ) against pH, what kind of line will it make?

What will the Y intercept be equal to?

Back 137

A straight line.

The Y intercept is equal to the log of Ka*S0

*equation: intercept/S0 = log ka

Front 138

Weak basic drugs are more soluble in what type of solution?

Back 138

In acidic solution where the ionized form of drug is predominant.

Front 139

What is the solubility equation for weak bases?

Back 139

Kb/[OH-] = [H]/Ka = S-S0/S0

Front 140

To use the solubility equation, what do you need to know?

Back 140

*pka

*solubility of unionized/undissociated species

Front 141

What is the solubility equation for weak bases?

Back 141

pH - pKa = log S0 / S-S0

Front 142

Linearize the solubility equation for weak bases.

Back 142

log (S - S0) = -pH + log Ka*S0

Front 143

In a weak base, when you plot log (S - S0) against pH, what does the profile look like?

Back 143

A straight line with a negative slope. The Y

intercept is equal to log ka*S0

Front 144

The lower the pKa, the stronger the...

Back 144

weak acid

Front 145

The lower the pKb, the stronger the...

Back 145

weak base

Front 146

What type of graphing paper should you use when you have exponents, and why?

Back 146

Semi-log paper because it makes a linear line

Front 147

What is the equation with temperature and solubility?

Back 147

S = K e^-deltaHs/RT -or-

ln S = ln K - deltaHs/RT

Front 148

What is delta Hs?

Back 148

The heat of solution--it tells us the influence of temperature on solubility

Front 149

A plot of log of solubility (y axis) vs. reciprocal of absolute temp (1/T...x axis) will give what type of line? What will the slop allow you to determine?

Back 149

A straight line on semi-log paper.

The slope lets you determine the value of delta Hs.

-deltaHs = slope x 2.303 x R

Front 150

When the following equation has a negative slope, slope is zero, and slope is positive--what does that mean for deltaHs?

-deltaHs = slope x 2.303 x R

Back 150

*negative slope = positive deltaHs

*slope is zero=horizontal line=deltaHs is 0k/cal/mole=temp has no influence

*positive slope= negative deltaHs

Front 151

The higher the value of deltaHs...

Back 151

the greater the influence of temperature on

solubility.

Front 152

If the value of deltaHs (heat of solution) of a drug/solute is know, what can you predict?

Back 152

You can predict the solubility of a drug at a

different temperature with an equation.

log S(T2)/ S(T1) = deltaHs/2.303*R * T2-T1/T1xT2

Front 153

Can heat of solution be positive and negative?

Back 153

Yes, it can be both positive and negative

Front 154

If the heat of solution is negative, increasing the temperature will...

Back 154

decrease the solubility of the drug.

Front 155

The negative value of heat of solution indicates that...

Back 155

heat must be released from the solute for it to dissolve. Heat will be given off as the solution is being formed. Increasing temperature will add more heat and less solute will dissolve.

Front 156

If the heat of solution is positive, a solvent at higher temperature will...

Back 156

dissolve more solute than it will at lower temperatures.

Front 157

The higher the value of heat of solution, the more pronounced will be...

Back 157

the effect of temperature on the solubility of the drug.

Front 158

If the heat of solution is small, there is what type of effect on the temperature? (for example, 1 Kcal/mole)

Back 158

There is essentially no effect on the solubility of a drug at higher or lower temperatures.

Front 159

What are the units for heat of solution?

Back 159

Kcal/mole

Front 160

Aspirin. Is it a weak acid or weak base? What are 3 uses for it? When is it stable? Does it have a smell?

Back 160

*weak acidic

*analgesic, anti-pyretic, anti-inflammatory

*stable in dry air

*odorless, but in moist air it gradually hydrolyzes into salicylic acid and acetic acid and acquires the odor of acetic acid

Front 161

Lorazepam

What dosage forms are available? What strengths are they in?

Back 161

*tablets: 0.5mg , 1mg, 2mg

*injection: 2mg/ml in 10 mL vials or 4mg/mL in 10 mL vials

*oral solution (intensol): 2mg/mL (alcohol and dye free)

Front 162

What are the inactive ingredients in Lorazepam Intensol? What color is the powder form of it and what is its solubility in water?

Back 162

Inactive ingredients: polyethylene glycol and propylene glycol (co-solvents are needed to make clear solution possible)

*it is white powder and is almost insoluble in

water

Front 163

What is polymorphism? In what form does it

exist?

Back 163

*this is when a drug exists in more than one crystalline form with the same pharmacologic activity, but the arrangement is different

*physical chemical property

*not all chemical products have this

*exists only in powder form

*only in solid state

Front 164

What is the definition of polymorphism?

Back 164

This is a phenomenon where a substance may be capable of crystallizing in more than one crystalline form.

Front 165

Two polymorphs will be different only in their...

Back 165

crystal structure.

Front 166

When will two polymorphs be identical?

Back 166

in liquid and vapor states

Front 167

Do isomers have the same melting point? When they melt, how will their compositions compare in liquid form?

Back 167

No, they will melt at different temperatures and will melt into liquid of different compositions.

Front 168

True/False

Different polymorphs of a give compound, are as different in structure and physical chemical properties as crystals of two different compounds.

Back 168

True

Front 169

In polymorphs, is the aqueous solubility the same? How will this be reflected?

Back 169

They are different. It is reflected in the dissolution rate. If the dissolution rate is different, it will be reflected in the bioavailability.

Front 170

What is rate of dissolution?

Back 170

How rapid the drug is dissolving in the surrounding fluid

Front 171

What are some physical chemical properties that must be considered when studying polymorphs?

*all these properties can vary when polymorphic forms

Back 171

*aqueous solubility

*melting point

*true density

*hardness

*crystal shape

*optical/electrical properties

*physical chemical stability

Front 172

Will polymorphs have the same physical chemical stability?

Back 172

No--they can be different. Some will be more stable than others--you could have problems with expiration dating if you select the unstable version.

Front 173

How are different polymorphic forms identified?

Back 173

Each form is give a roman numeral or greek letter

Front 174

True/False

Polymorph form I is generally the most stable at room temperature--other forms are numbered in order of discovery.

Back 174

True

Front 175

Do you want the stable or unstable polymorphic form?

Back 175

You want the meta-stable form that is thermodynamically unstable but high in energy

Front 176

What is theobroma? What is it used to make?

Back 176

*cocoa butter

*base for suppositories and suntan lotions

*has a low melting point (36 to 37C)

*when compounding, keep it around 36C to keep it from becoming another polymorphic form

Front 177

What two dosage forms is progesterone available in?

Back 177

soft gelatin capsules and suppositories

Front 178

What are the three reasons why polymorphism happens?

Back 178

*molecular shape change

*structural change

*rotational disorder change

Front 179

What are structural changes in polymorphism?

Back 179

The crystal lattice exhibits bending and breaking and can cause different physical chemical properties

*rapid transformation due to breaking of lattice

Front 180

Polymorphism is the result of...

Back 180

different arrangements of molecules in the solid state and the shape of these molecules may be different in different polymorphs

Front 181

The shape change of polymorphs may be restricted to...

Back 181

the rotation of parts of molecules about certain bonds and minor distortions of bond distances and angles

Front 182

What can produce molecular shape change in polymorphs?

Back 182

Change in relative positions of adjacent molecules may influence the polarizability effects of one molecule on another--this produces distortions of molecular shapes.

Front 183

When does rotational disorder happen in polymorphs?

Back 183

It is due to the breakage of weaker bonds of a compound followed by the rotation of the part of the molecule about the fixed structure.

*rapid transformation

Front 184

What are the two classifications of polymorphs?

Back 184

Enantiotropic and monotropic

Front 185

What is enantiotropic classification of polymorphs?

Back 185

When the change from one polymorphic form to another form is REVERSIBLE by varying TEMP or PRESSURE

Front 186

What is mono tropic classification of polymorphs?

Back 186

When the transition from one form to another form takes place in ONLY ONE direction (IRREVERSIBLE)

*from meta-stable form to stable form or unstable polymorphic form at all temps and pressures

Front 187

Why is the meta-stable form more desirable in pharmaceutics?

Back 187

It is higher in energy, lower in melting point, and higher in solubility.

*pharmaceutical importance depends on the rapidity of the transition to a stable form and the nature of the altered physical chemical properties

Front 188

In the drug discovery group, what can cost the company millions of dollars if this step is forgotten?

Back 188

The initial task of scientists is to determine where a drug being investigated exists in more than one crystalline form.

Front 189

In what dosage form can you take advantage of the meta-stable form?

Back 189

tablets and hard gelatin capsules

*powder form only

*can have good expiration dating near 2 years

Front 190

What are some different ways to identify polymorphic forms?

Back 190

*microscope *fusion method (hot stage microscopy)

*differential scanning calorimetry *infrared spectroscopy

*x-ray powder diffraction *scanning electron microscope

*thermo-gravimetric analysis *dissolution/solubility analysis

--each method requires a very small amount of powder (2mg to 500mg)

Front 191

How do you perform a dissolution/solubility analysis?

Back 191

You take a therapeutic agent and put it in a test tube with water and dissolve it. You use a

seeding technique to try and recrystallize it.

Front 192

What is the relationship between melting point and solubility of polymorphic forms?

Back 192

Low melting point has high solubility

--due to molecules not being as compact

Front 193

What was the first application of polymorphism?

Back 193

Antibiotic for typhoid--it is insoluble

*also called chloramphenicol palmitate

*has 3 crystalline forms (A, B, C)

*peak serum levels of it increased when form B was used in greater amounts (dose is the same)

Front 194

Crystalline compounds might contain what type of solvent?

Back 194

crystallization solvent

Front 195

What happens to a crystallization solvent when it is entrapped in water?

Back 195

The crystalline powder is called hydrate and it becomes either hemi-hydrate (1/2 molecule),

mono-hydrate (1 molecule), di-hydrate (2

molecules), or tri-hydrate (3 molecules) of water.

Front 196

What is a compound that does not contain any water within its crystal structure called?

Back 196

anhydrous

Front 197

Why is it important to identify possible hydrate compounds in the pre-formulation studies?

Back 197

Their aqueous solubility can be significantly less than their anhydrous form.

Front 198

Conversion from anhydrous to hydrate form within a the solid dosage form may...

Back 198

reduce the dissolution rate, which may in turn reduce the rate and extent of absorption.

Front 199

What is bioavailability?

Back 199

The rate and extent of absorption

Front 200

Is the anhydrous for desirable? Why?

Back 200

Yes, because it has greater solubility that is

reflected in its bioavailability

Front 201

What is pKw equal to? What equation is it associated with?

Back 201

*It is equal to 14

*pKw= pKa + pKb