L14 - Pre-formultaion Of Solid Dosage Forms 1

Question 1

What does the design of any dosage form deal with?

Answer 1

The conversion of a new chemical entity (NCE) into a deliberable medicine

Question 2

What is the main aim in the design of any dosage form?

Answer 2

To facilitate the delivery of therapeutic into the body

Question 3

How do you want to facilitate the delivery of therapeutic drugs into the body?

Answer 3

• safely
• efficiently
• reproducibly
• conveniently

Question 4

What is preformulation?

Answer 4

The first step in the rational development of dosage forms of a drug into a medicine

Question 5

What does preformulation involve?

Answer 5

Characterising the physical and chemical properties of the active pharmaceutical ingredients

Question 6

What does preformulation provide?

Answer 6

Provides the formulating team the critical info for developing a stable and bioavailable dosage form that can be mass produced

Question 7

What is the aim of preformulation exercise?

Answer 7

Produce a mathematical based model for drug behaviour in the proposed dosage form both in vitro and in vivo

Question 8

What is the first step in the preformulation for gastro-intestinal delivery?

Answer 8

The drug must dissolve before it can permeate the gut epithelium and enter the systemic circulation

Question 9

What can the solubility and dissolution rate be a controlling factor of?

Answer 9

Rate of absorption and bioavailability of a medicine

Question 10

What is the optimal aq solubility?

Answer 10

Aq solubility greater than 10mg/mL

Question 11

What happens when the solubility of the drug < 1mg/mL?

Answer 11

Then a salt form of the drug, if possible, is indicated

Question 12

What is the Biopharmaceutical clssification system (BCS)?

Answer 12

Class I
- high solubility & high permeability

Class II
- low solubility & high permeability

Class III
- high solubility & low permeability

Class IV
- low solubility & low permeability

Question 13

What are high risk compounds?

Answer 13

Pooly soluble compounds
(Defined by the FDA BCS (Class II, IV)

Question 14

What may compounds require to enhance dissolution rate and bioavailability via the GI tract?

Answer 14

One of the non-equlibrium methods or semi-solid/liquid formulations

Question 15

What are the formulationsthat enhance dissolution rate and bioavailabiliity via the GI tract?

Answer 15

• amorphous
• meta-stable polymorphs
• solid dispersion
• lipid based formulations

Question 16

Why is minimum wastage important? So what is the most critical decision?

Answer 16

Only a limited amount of compound made available from the drug discovery team

• which compound, salt or polymorphic form to proceed into development

Question 17

What happens to the solubility if a drug has ionisable groups?

Answer 17

Solubility will change as a function of pH

Question 18

What is salt fomration a critical solution for?

Answer 18

The selection of more lipophilic and water insoluble comounds due to search of more potent and highly specific drug molecules

Question 19

Why is the salt form choice an important step in the development process?

Answer 19

• has an impact on physicochemical and biopharmaceutical properties

Large effect on
- quality
- safety
- efficafy of medicine

Question 20

When is conversion of a salt form beneficial? What can happen to properties?

Answer 20

If a drug candidate has poor aq solubility and is a WB/WA
- many physicochemical properties may change

Question 21

What does salf formation require in terms of pKa?

Answer 21

Sufficient difference in pKa between the acid and the base (delta pKa = 3)

Question 22

What are the advantages of pharmaceutical salts?

Answer 22

• enhance solubility
• inc dissolution rate
• easier synthesis and purification
• better taste
• improved photostability
• high bioavailability
• higher mp

Question 23

What are disadvantages of pharmaceutical salts?

Answer 23

• dec % of drug
• inc hygroscopicity
• additional manufacturing steps
• inc toxicity
• dec chem stability
• no change in solubility at dif pH in GI tract
• inc num of polymorphs

Question 24

What factors are considered when target salts are chosen?

Answer 24

• structure of drug substance
• pKa
• chem and phy stability
• available lit on structurally-related compounds
• eas of large-scale production
• type of drug product
• anticipated loading of the drug