Considerations in the design and performance of drug products Flashcards
Define biopharmaceutics.
What is the role of biopharmaceutics?
manufacturing factors and physiochemical properties that influence rate and extent of drug absorption from site of administration
To link in vivo product performance to the manufacturing properties and physiochemical properties of the drug.
in vivo product performance refers to
BA, onset, safety, efficacy
Why is establishing an IVIVC helpful in drug development?
Establishes a relationship between a biological property of the drug such as PD effect or plasma conc’n and a physiochemical property of the drug product containing the drug substance such as dissolution.
It connects lab data (like dissolution) with what happens in the body (like plasma concentration or drug effect).
Extent of drug absorption parameters
rate of drug absorption parameters
AUC
C and T max
List biopharmaceutic considerations when creating a formulations.
- Drug substance
- Drug product
- PD
- Patient
- Manufacturing
What are the Pharmacodynamic considerations?
This relates to the response you want to achieve.
refer to the effects a drug has on the body and how it works (its mechanism of action).
It includes the therapeutic response and the adverse drug reactions.
Example nitroglycerin – highly metabolized if swallowed
plasma concentration vs. time curves for GTN given through different routes of administration.
Describe various routes of administration of GTN and how they affect onset and duration?
Sublingual Very rapid rise → very fast effect, but short duration.
Oral Slower rise and fall → slower effect, longer-lasting.
Ointment Gradual absorption and long duration → good for steady effect.
Disc Flat, steady curve → slow release over a long time (good for sustained therapy).
IV (Intravenous) Instant high level → immediate effect, maintained until stopped (“IV off”).
Buccal Similar to oral but faster onset; depends on how fast the tablet dissolves.
Sublingual has the shortest onset of action and the shortest duration
Transdermal infusion has the longest onset and longest duration
What are the drug substance considerations?
you need to consider the five stages of drug development.
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)
consider using in silico drug design: using computers and mathematical models to help design or predict how drugs might work.
PK/PD modelling and simulation (quantitatively assess dose/exposure- response relationships)
consider the Genetic differences/polymorphisms of CYP2D6 and CYP2C19 enzymes (results in extensive/poor metabolisers of the drug
- Pharmacogenomics application with development and clinical trials. This is the science of using your genetic information to choose the right drug and dose for you.
What are the drug product considerations?
The bioavailability of the drug in its dosage form determines the concentration at the site of action which impacts the pharmacological response and efficacy.
Factors affecting how much of the drug absorbed at site
physiochemical properties, Stability of the drug in the GIT, first pass effect
For example: If a drug is not well absorbed orally or requires high doses that could lead to toxicity, alternative routes of administration are considered.
What are the dose considerations?
Doses may need to be altered for individualized dosing due to differences in PK parameters (metabolism, renal clearance, weight, Vd, age, disease stage)
Dose titration is the gradual adjustment of drug dosage to achieve the desired therapeutic effect while minimizing side effects.
So companies tend to have different strengths and scored tablets to adjust dose.
Remember that the Dose = drug +excipients
You need to consider the ease of swallowing of solid oral dosage forms. A capsule may be easier than a large round tablet and large amount of fluids helps swallowing difficulties.
What are the dosing frequency considerations?
Remember increasing frequency of a dose can keep drug concentration above mec but can be inconvenient.
The therapeutic dosage regimen includes dose (amount taken at one time), dosing freq/dosage regimen (freq at which drug doses are given) and total daily dose (dose and freq).
Dosing freq determined by drug clearance and target plasma concentration.
For example: 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 (Remember Extended Release drugs have a problem with dose dumping)
What are the patient considerations?
Patient Compliance (Passive Following of Instructions)
Patient Adherence (Active Participation in Treatment)
Drug product and therapeutic regimen must be acceptable to patient.
Poor patient compliance as a result of poor product attributes (bitter taste, swallowing problems, SEs, odor)
You can improve compliance with special packaging, ODT (orally disintegrating tablets) and chewables which can be beneficial for some patients.
For example antiepileptic drugs can be given via Transmucosal (nasal) administration rather than rectal administration as it is more convenient, easier to use and safe.
Explain the concept of drug product design and performance using route of administration
List the emergency routes of administration
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
