Biopharmaceutical Considerations Part 1 Flashcards
What are the factors that affect GIT site absorption?
- Drug substance (API) properties (pH, solubility, ionisation.
- How drug product is formulated (dosage form)
- Site of administration (better absorption with many blood vessels present)
What steps must occur for absorption to take place?
- drug must be released from the formulation/product (except oral solutions)
- enter into the gut lumen’s fluids/juices
- dissolved free drug diffuse to the gut wall epithelia
What is dissolution vs drug release?
Dissolution: processes (e.g disintegration or capsule rupture) that cause solvation of drug substance from orally administered IR solid drug products/ dosage forms
Drug release: drug release of non-oral dosage forms (i.e. topical, transdermal, suppositories, liposomal delivery, etc.)
What are the Processes Affecting Extent of Absorption During GI Transit?
- Drug substance degradation
- Precipitation
- Motility
- Gut wall/intestinal metabolism
- First-pass metabolism
6.Drug disposition (distribution and elimination)
What is drug disposition?
combination of processes ADME resulting in a particular drug exposure within an individual.
They will all influence the level and kinetics of drug exposure to the tissue.
Elimination includes the processes Excretion and metabolism. T/F
True
Explain how drug products are designed for locally acting drugs.
- designed to deliver the drug directly to the site of action before reaching the systemic circulation to limit systemic drug absorption.
- designed to penetrate no further than the local tissue
- administered orally (local GI effect) or applied topically
Rate of drug release and absorption is generally quantified by (Tmax) and (Cmax).
T/F
The extent of drug release and absorption is represented by (AUC)
T/F
True
True
What are the biopharmaceutic factors that affect Drug Product design?
These are also Factors affecting BA (or Drug-System properties
- Drug substance properties
- Formulation of the drug product
- Biological characteristics of the patient
- Excipients:
(are inert concerning pharmacodynamic activity
important in manufacture and functionality of drug product) - Drug disposition influenced by specific formulation of the drug
(For example, encapsulated drug in liposomes/microspheres may change the drug distribution and systemic clearance
addition of mannitol may change the renal clearance)
What are the Considerations in the Design of a Drug Product?
- Physiochemical properties of the drug substance
- Route of drug administration
- Desired PD effect
- Toxicologic properties of the drug substance and excipients
- Effect of excipients and dosage form
- Manufacturing processes
Considerations for route of administration.
- Anatomy and physiology of the administration site
- Ingredients to be used
Biopharmaceutic Considerations determine the dose and dosage form of a product.
T/F
True
and remember
Strengths of a dosage form usually expressed in unit
Dose adjusted based on weight or surface area
What are the Rate Limiting Steps in Drug Absorption?
- Delivery of drug product formulation
- Release of the drug substance from the formulation
- Transportation to absorption site (cellular permeation)
4.For non-locally acting drugs, post absorption, rate dependent steps - ER formulation, the release of the drug from the formulation is the rate limiting step
- For solid oral IR tablets, disintegration (rate limiting step)
What are the rate limiting steps for ER and IR formulations?
ER: release of the drug from the formulation
IR: disintegration
What is disintegration?
process by which dosage forms progressively transforms to smaller drug particles.
eg of dosage form Chewable tablets, troches, liquid filled soft gelatin capsules, SR drug products (osmotic pump, etc. oral dosage forms)
Examples of disintegrants.
Na starch glycolate
crospovidone,
microcrystalline cellulose
What are the mechanisms of disintegration?
wicking: the disintegrant pulls water into pores
reduce physical bonding force between particles.
swelling: particles swell creating localized stress that spreads and breaks up matrix from within
What two factors can result in poor disintegration?
High compression or insufficient disintegrant
When should you use disintegration instead of or in lieu of dissolution.
1.The product under consideration is rapidly dissolving
2.The drug product contains drugs that are highly soluble throughout the physiological range
3.A relationship to dissolution has been established or when disintegration is shown to be more discriminating than dissolution
4.In vitro dissolution cannot be practically characterized for highly soluble compounds
What is dissolution?
What is solubility?
The process by which a solid drug substance becomes dissolved in a solvent over time (dynamic)
Solubility is the mass of solute that dissolves in a specific mass or volume of solvent at a given temperature (equilibrium)
If a drug has poor aqueous solubility (does not dissolve well in water-based fluids like stomach or intestinal fluids), its dissolution rate becomes the rate-limiting step in drug absorption.
T/F
True
What is IVIVC?
in-vitro-in-vivo correlation)
If there is a strong correlation between in-vitro (lab) and in-vivo (body) dissolution, scientists can use in-vitro tests to predict how the drug will behave in the body.
ie. where experimental dissolution data helps quantitatively predict bioavailability (BA) without needing excessive human/animal trials
Noyes and Whitney Equation
studied how substances dissolve in water, using benzoic acid and lead chloride as examples.
Propose that saturated solution film allows for diffusion to take place
Rate of dissolution is proportional to the difference between the saturation solubility and the instantaneous bulk (well-stirred) concentration
According to The Noyes-Whitney equation dissolution is influenced by:
1.Physiochemical characteristics of the drug
2.The solvent the drug is dissolving in
3.Level of agitation in the bulk fluid medium
4.Temperature of the fluid medium (solvent
What are the Factors Affecting Drug Dissolution in Solid Oral Dosage Form?
- The physical and chemical nature of the active drug substance
- The nature of the excipients
- The method of manufacture
- The dissolution test conditions
How is particle size related to drug absorption?
Smaller particles have a greater surface area.
This results in fast rate of dissolution.
And rapid drug absorption
