RE lecture 1

Question 1

How is onset/release of a drug controlled?

Answer 1

1. rapid onset: use injections or inhalation
2. for prolonged onset: use extended release tablets
3. for targeted release: nanomedicines

Question 2

How are medicines protected from the gastric environment of the stomach?

Answer 2

Enteric coated tablets

Question 3

How are drugs delivered if they want to bypass first pass metabolism?

Answer 3

Drugs that don’t pass through the GI tract eg: injections, creams, sublingual etc

Question 4

How to improve patient’s acceptance to the drug?

Answer 4

1. mask undesirable odour
2. mask undesirable taste

Question 5

What happens before preformulation?

Answer 5

primary characterisation of drug and excipients

Question 6

Why are preformulation studies important?

Answer 6

1. Learn about the physical and chemical properties of the candidate drug and excipients
2. This allows for quick remediation action when a problem arises
3. ensures the quality of the drug

Question 7

What is polymorphism?

Answer 7

Change in physical state of the drug, but not the chemical state

Question 8

What is the drawback of a drug being insoluble in water?

Answer 8

1. Poor dissolution in the GI tract–> less absorption into the bloodstream—> low bioavailability
2. hard to develop medicines that can be administered non-orally

Question 9

What are parenteral formulations?

Answer 9

Dosage forms that are administered non-orally.

Question 10

What are the differences between crystalline and amorphous states?

Answer 10

1. Crystalline forms have a definite ordered internal structure while amorphous forms have no fixed internal structures
2. Crystalline forms are more stable that amorphous forms as they have lower internal energy.
3. Crystalline forms are less soluble than amorphous forms.
4. Crystalline forms have less inclination to change its from during storage than amorphous forms.

Question 11

What are the different types of API solid states?

Answer 11

1. amorphous
2. form 1
3. form 2
4. solvates/hydrates
5. salts
6. cocrystals

Question 12

What are polymorphs?

Answer 12

Crystalline forms with the same chemical composition but different internal structures (packing, conformation, etc)

Question 13

Define preformulation.

Answer 13

Primary characterisation of a drug and excipients for certain fundamental physical and chemical properties.

Question 14

What does it mean for a drug to be hygroscopic?

Answer 14

It absorbs moisture from the air

Question 15

What are the commonly evaluated physical parameters during preformulation?

Answer 15

1. Solubility and permeability
2. BCS classification
3. Solid state properties
4. Polymorph screen
5. Salt screen
6. Amorphous solid dispersion screen.

Question 16

Why is it important that a drug be soluble in water?

Answer 16

The drug must be in solution to be absorbed.

Question 17

What is the biopharmaceutical classification system?

Answer 17

A scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.

Question 18

When is a drug considered as highly soluble?

Answer 18

When its highest dose strength is soluble in about 250ml of water over a pH range on 1 to 7.5

Question 19

When is a drug considered to be highly permeable?

Answer 19

When the extent of absorption in humans is determined to be more than 90% of an administered dose, based on mass balance or in comparison to an IV reference dose

Question 20

What are the different BCS classifications and what do they mean?

Answer 20

1. BCS class I: high solubility and permeability
2. BCS class II: low solubility and high permeability
   3.BCS class III: high solubility and low permeability
3. BCS class I: low solubility and permeability

Question 21

What is the function of polymorph screening?

Answer 21

Assess all the polymorph structures to select the most thermodynamically stable form

Question 22

Are hygroscopic substances desirable as drugs?

Answer 22

No

Question 23

What is the function of salt screening?

Answer 23

To make a salt form of the API so that it can be more soluble in water.
Salt forms may also improve melting point and stability

Question 24

Why do BCS class I compounds not need salt screening

Answer 24

Because the compound is already very soluble in water.

Question 25

Why is it important that the API doesn’t exhibit complex polymorphic behaviour?

Answer 25

If the drug polymorph changes during storage or transport, it could affect solubility and stability

Question 26

When is amorphous solid dispersion screening done?

Answer 26

When the other methods of screening do not produce a soluble compound

Question 27

What is done during ASD screening?

Answer 27

The API is mixed with a polymer and sometimes a surfactant

Question 28

Why is a polymer used to make ASD?

Answer 28

The polymer stabilises the amorphous state of the API in the solid form to prevent recrystallisation during dissolution.

Question 29

ASD’s are normally formulated as what dosage form?

Answer 29

Tablets

Question 30

What is thermodynamic and kinetic solubility?

Answer 30

1. Thermodynamic solubility measures to what extent a solute dissolves
2. Kinetic solubility measures to what extent the solute precipitates

Question 31

Is thermodynamic or kinetic solubility the gold standard for solubility?

Answer 31

Thermodynamic solubilty

Question 32

F