Considerations in the design and performance of drug products

Question 1

Define biopharmaceutics.

Answer 1

manufacturing factors and physiochemical properties that influence rate and extent of drug absorption from site of administration

Question 2

Extent of drug absorption parameters
rate of drug absorption parameters

Answer 2

AUC
C and T max

Question 3

List biopharmaceutic considerations when creating a formulations.

Answer 3

1. Drug substance
2. Drug product
3. PD
4. Patient
5. Manufacturing

Question 4

One biopharmaceutic consideration is
DRUG SUBSTANCE
What do you need to consider in relation to this?

Answer 4

you need to consider
1. the stages of drug development
2. in silico drug design (based on computational methods)
3. PK/PD modelling and simulation (quantitatively assess dose/exposure- response relationships)
4. Genetic polymorphisms of CYP2D6 and CYP2C19 enzymes (results in extensive/poor metabolisers
5. Pharmacogenomics application with development and clinical trials.

Question 5

One biopharmaceutic consideration is
DRUG PRODUCT
What do you need to consider in relation to this?

Answer 5

1. BA of drug in particular dosage form
2. Pharmacological response related to drug concentration at site of action
3. Factors affecting how much of the drug absorbed at site e.g. physiochemical properties
4. Stability of the drug in the GIT
5. Poor BA due to first pass hepatic metabolism.
6. If a drug is not well absorbed orally or requires high doses that could lead to toxicity, alternative routes of administration are considered.

Question 6

One biopharmaceutic consideration is
DOSE
What do you need to consider in relation to this?

Answer 6

1. Dose alteration due to differences in PK parameters (metabolism, renal clearance, weight, Vd, age, disease stage)
2. Dose titration
3. is the tablet scored
4. Dose = drug +excipients (size)
5. Size and shape of solid oral drug products (ease in swallowing and Large amount of fluids helps swallowing difficulties)

Question 7

One biopharmaceutic consideration is
DOSING FREQUENCY
What do you need to consider in relation to this?

Answer 7

1. Therapeutic dosage regimen (dose, dosing freq, total daily dose)
2. dosage regimen
3. If drug has a short half life or rapid clearance from the body, the drug must be given more frequently or administered as an ER drug product

Question 8

One biopharmaceutic consideration is
PATIENT
What do you need to consider in relation to this?

Answer 8

1. Drug product and therapeutic regimen must be acceptable to patient
2. Poor patient compliance as a result of poor product attributes (bitter taste, swallowing problems, SEs, odor)
3. special packaging, ODT and chewables can be beneficial for some patients
4. Transmucosal (nasal) administration of antiepileptic drugs (more convenient, easier to use, safe) vs rectal administration

Question 9

Explain the concept of drug product design and performance using route of administration
List the emergency routes of administration

Answer 9

Route of administration affects the rate and extent (BA) of the drug
This can alter onset, duration, intensity of the pharmacological response
It can Increase efficacy and reduce toxicity/SEs

Emergency routes – rectal, nasal, buccal mucosa

Question 10

What is the role of biopharmaceutics?

Answer 10

It is the link between in vivo product performance to the drug product’s manufacturing and physiochemical properties

in vivo product performance refers to
BA, onset, safety, efficacy

Question 11

What is meant by in vitro - in vivo correlation?

Answer 11

Establishes a relationship between a biological property of the drug (e.g.PD effect or plasma conc’n) and a physiochemical property of the drug product containing the drug substance (e.g. dissolution)

Question 12

What are the PD considerations?
This relates to the response you want to achieve.

Answer 12

1. Effect of drug in the body
2. mechanism of action
3. therapeutic response
4. ADRs

Example nitroglycerin – highly metabolized if swallowed

Question 13

What are the five stages of drug development?

Answer 13

1.Disease target identification
2.Target validation
3.High-throughput identification of drug leads
4.Lead optimization
5.Preclinical and clinical evaluation

stages 3-5 involves characterization of the PK properties (ADME)

Question 14

What is dose titration?

Answer 14

Dose titration is the gradual adjustment of drug dosage to achieve the desired therapeutic effect while minimizing side effects.

Question 15

Remember Extended Release drugs have a problem with dose dumping.

Question 16

Remember increasing frequency of a dose can keep drug concentration above mec but can be inconvinient.

Question 17

Define
Dose
Dosage regimen
Total daily dose

What two things determine Dosing freq

Answer 17

dose is the amount taken at one time (mass, volume, number (puffs/drops)

Dosage regimen is the freq at which drug doses are given

Total daily dose includes dose and freq

determined by drug clearance and target plasma concentration

Question 18

Patient compliance vs adherence

Answer 18

Patient Compliance (Passive Following of Instructions)
Patient Adherence (Active Participation in Treatment)

Question 19

Desribe various routes of administration of GTN and how they afffect onset and duration?

Answer 19

Sublingual has the shortest onset of action and the shortest duration
Transdermal infusion has the longest onset and longest duration