Week 4 - Pharmaceutics (Thermodynamics)

Front 1

Entropy: Though Experiments

Back 1

Mechanical Equilibrium

Hint 1

Ball on the top of the incline: potential energy (gravitational) due to position. When released, potential energy will convert to heat (friction) and to kinetic energy as it rolls down). At rest, potential energy equals zero, thus the ball is at a mechanical equilibrium.

Front 2

Experiment # 2

Back 2

Dissolve NaOH in water

Solution becomes warm - heat is released

Front 3

Experiment #3

Back 3

Dissolve Solid NaNO3 in water

Solution becomes cool, heat is absorbed

Front 4

Experiment # 4

Back 4

Two identical chambers (A&B) connected by a stopcock

Front 5

What is Entropy

Back 5

A thermodynamic property that is the measure of a systems thermal energy per unit temperature that is unavailable for doing useful work.

Front 6

What is thermodynamic entropy?

Back 6

Is more generally define from a statistical thermodynamics viewpoint in which the molecule nature of matter is explicitly considered. Another thought experiment.

Front 7

The N number of molecules in this system the probability that at equilibrium all N molecules will be found in … ?

Back 7

Left chamber is (1/2)^N

Hint 7

Entropy : Probabilistic Explanation

Front 8

The probability that the molecules will be …

Back 8

Distributed equally between chambers will increase

Hint 8

Entropy: Probabilistic Explanation

Front 9

Entropy is the measure of ?

Back 9

“Randomness” or “Disorder”

Front 10

The second law of thermodynamics:

Back 10

All natural processes occur only in one direction—— one that leads to minimum potential energy

Front 11

Entropy change can be mathematically expressed as:

Back 11

dS = dH/T or S = H/T

Front 12

The Third Law of Thermodynamics:

Back 12

The entropy of a perfect material at absolute zero is exactly equal to zero.

Front 13

It is impossible to cook any system to T equals to 0 K, so..

Back 13

S is always positive.

Front 14

What is Gibbs Free Energy

Back 14

Combines these two factors and it is a state function:

Hint 14

G = H - TS

This has an energy component and an entropic component

Front 15

What is incremental form?

Back 15

Used most commonly to determine the change in free energy

Hint 15

G = H - T S

Front 16

For a process to occur spontaneously, the G term should have a ?

Back 16

Negative value (energy minimization)

Front 17

Equilibrium is the position where …

Back 17

G = 0

Front 18

The process during which the “heat content” of the system remains constant is known as an …

Back 18

Adiabatic process

Hint 18

Application of Thermodynamic Principles in Pharmacy

Front 19

‘The entropy of a perfect material at absolute zero is exactly equal to zero.’ This statement is a description of … ?

Back 19

3rd law of thermodynamics

Front 20

‘The entropy of a perfect material at absolute zero is exactly equal to zero.’ This statement is a description of … ?

Back 20

3rd law of thermodynamics

Front 21

For an EXOTHERMIC reaction, which one of the following is true?

Back 21

Change in enthalpy (H) is negative

Front 22

Front (Term)

Back 22

D-1

Front 23

Front (Term)

Back 23

D-1

Front 24

Chemical Kinetics and Drug Stability Introduction

Back 24

A pharmacist interrupts information related to drug stability provided by the manufacturer and relays it to the patients.

Hint 24

He/she recommends proper storage and use of dosage forms.

Front 25

What are the 5 types of stability ?

Back 25

Back (Definition)

Front 26

Physical stability

Back 26

Back (Definition)

Front 27

Chemical stability

Back 27

Influenced by chemical structure, environmental and formulation factors

Front 28

Oxidation-Reduction

Back 28

Major cause of drug instability

Front 29

Autoxidation: Functional Groups

Back 29

Back (Definition)

Front 30

How can Photolysis be prevented?

Back 30

Suitable packaging in amber colored bottles

Cardboard Outers

Aluminum foil over wraps

Front 31

Oxidation: Prevention

Back 31

Use carefully chosen antioxidants

Minimize exposure

Eliminate trace metals

Light resistant

Refrigeration and maintaining pH

Front 32

What is hydrolysis?

Back 32

Drugs containing ester, amide, imide, imine, and lactam functional groups are prone to hydrolysis.

- Often a pH-dependent reaction involves solvolysis, a process in which a drug molecule interacts with a water molecules to yield breakdown products.

- Buffers - used to maintain the pH at which drug stability is optimum.

- The amount of water present in formulation affects the rate of hydrolysis.

Front 33

What is inter-ionic compatibility and decarboxylation?

Back 33

Chemical instability caused by addition of a large ionic species with a charge opposite to that of a drug.

Decarboxylation - Involves removal of the carboxyl group from a drug molecule

Front 34

Racemization

Back 34

Process of changing from an optically active compound into a race mix compound or optically inactive mixture of ‘R’ and ‘S’ forms

Front 35

Epimerizarion

Back 35

A chemical reaction leading to formation of an epimer of the active compound. Epimers are diastereomers with difference in chirality only at one sterogenic center

Front 36

Drug stability importance

Back 36

Back (Definition)

Front 37

Microbial Contamination: Sources

Back 37

Back (Definition)

Front 38

Expiration date : purpose

Back 38

Loss of active ingredient and potency due to decomposition of drug

Decomposition products can be harmful

Physical changes can decrease the efficacy

Front 39

Reaction rate

Back 39

The velocity with which a reactant(s) undergoes a chemical change

Front 40

Reaction rate: Factors

Back 40

Back (Definition)

Front 41

Law of Mass Action

Back 41

Back (Definition)

Front 42

Law of Mass Action

Back 42

Back (Definition)

Front 43

Order of reaction: Zero Order Reactions

Back 43

Back (Definition)

Hint 43

Order of reaction: Zero Order Reactions

Front 44

Order of Reaction: First Order Reactions

Back 44

Back (Definition)

Front 45

Order of Reaction: Second Order Reactions

Back 45

Back (Definition)

Hint 45

Front 46

Order of Reaction: Second Order Reactions

Back 46

Back (Definition)

Hint 46

Front 47

Rate constants

Back 47

Back (Definition)

Hint 47

Half life is the time required for the reaction to reach half the initial concentration of the reactant ( 1/2 A0)

Front 48

What is Shelf life?

Back 48

Time required for 10% of the drug to degrade 90% of drug remains intact.

Front 49

Front (Term)

Back 49

Back (Definition)

Hint 49

Ea is always positive

The value of Ea does not change with temperature

Front 50

Stability testing

Back 50

Back (Definition)

Front 51

Shelf life estimation: Q10 Method

Back 51

Method based on Ea

Allows estimation of shelf-life for a product under different storage conditions

Hint 51

t90(T2) = t90(T1)/Q10 (T/10)

Where, Ea is the energy of activation, R is the gas constant and T is the absolute temperature

Front 52

Q10 Method (Cont.)

Back 52

Back (Definition)

Front 53

Other factors affecting reaction rates and stability

Back 53

PH , solvents, presence of additives/excipients, surfactants

Front 54

The statement, “In all spontaneous processes there is an increase in the entropy of the system and it’s surrounding,’ represents the … ?

Back 54

2nd law of thermodynamics

Front 55

“The entropy of a perfect material at absolute zero is exactly equal to zero.” The statement is a description of… ?

Back 55

3rd law of thermodynamics

Front 56

For an EXOTHERMIC reaction, which one of the following is true?

Back 56

Change in enthalpy (H) is negative

Front 57

Front (Term)

Back 57

D-1

Front 58

The statement, “In all spontaneous processes there is an increase in the entropy of the system and it’s surrounding,’ represents the … ?

Back 58

2nd law of thermodynamics

Front 59

Solubility: Introduction

Back 59

“The concentration of a solute when the solvent has dissolved all the solute it can at a given temperature.”

Or

“The concentration of solute in a saturated solution at equilibrium.”

Hint 59

Solubility is an intrinsic property of molecule and can only be modified by modifying the molecule chemically.

Dissolution is an extrinsic property and can be a influenced by complication, particle size, surface properties, and solubilization enhancement techniques.

Front 60

What is Miscible?

Back 60

When both solute and solvent are liquids and they form a solution over a wide concentration range (one phase)

Front 61

What is Saturated solution?

Back 61

One in which dissolved solute is in equilibrium with the solid phase.

Front 62

What is Saturated solution?

Back 62

One in which dissolved solute is in equilibrium with the solid phase.

Front 63

What is Unsaturated solution?

Back 63

A solution in which solute is present in a concentration below the concentration required for its complete saturation at a given temperature.

Front 64

What is Saturated solution?

Back 64

One in which dissolved solute is in equilibrium with the solid phase.

Front 65

What is Unsaturated solution?

Back 65

A solution in which solute is present in a concentration below the concentration required for its complete saturation at a given temperature.

Front 66

What is Supersaturated solution?

Back 66

- Contains more solute than a saturated solution

- It is very unstable, and solute generally precipitates out (due to equilibration) ups on agitation, seeding crystals, or scratching the container side.

Front 67

Solubility Expressions (USP)

Back 67

Back (Definition)

Front 68

Front (Term)

Back 68

Answers are above

Front 69

Types of Solvents

Back 69

Back (Definition)

Hint 69

Front 70

Intrinsic Solubility (S0)

Back 70

Solubilization is an equilibrium process.

At saturation solubility, the drug in solution is an equilibrium with solid drug

S0 = K = [Drug]solution/[Drug]solid

For non-electrolytes, S0 is same as the total solubility

Front 71

Factors affecting solubility/dissolution

Back 71

1. Chemical structure of the solute

2. Crystalline Vs. Amorphous forms

3. Polymorphs

4. Micronization

5. Temperature

Front 72

Factors Affecting Solubility/Dissolution

Back 72

Back (Definition)

Front 73

Factors Affecting Solubility/Dissolution

Back 73

Back (Definition)

Front 74

Factors Affecting Solubility/Dissolution

Back 74

Back (Definition)

Hint 74

Front 75

Front (Term)

Back 75

Back (Definition)

Hint 75

Front 76

Front (Term)

Back 76

Back (Definition)