Biopharmaceutics Flashcards
What is gastric residence time?
The length of time the medicine stays in the stomach
What is the most important physiological factor in biopharmaceutics?
Surface area of the GI tract
Where does most drug absorption occur?
The small intestine
Why are some drugs to be taken without food?
Liver enzymes also metabolise food so overloading enzymes with food means more drug escapes first pass effect
Process of dissolution
Formation of a diffusion layer occurs around particles made of GI fluid which forms due to interfacial tension between the drug and GI fluid
Diffusion layer is a barrier to drug dissolution and absorption
Drug particles must be wetted, dissolve and pass across the diffusion layer before it can be absorbed from the GI tract
What is ideal solubility?
The highest dose strength is soluble in <= 250ml of water over a pH range of 1-7.5
What is the Noyes-Whitney equation?
Dissolution rate = DA(Cs-C)/h
D = diffusion coefficient
A = surface area of drug particle in contact with GI fluid
Cs = Intrinsic solubility in the diffusion layer
C = drug conc. in GI fluid - negligible
h = thickness of diffusion layer around each drug particle
What is the easiest parameter to alter in Noyes-Whitney equation?
Surface area of drug particles
How can surface area of a drug be increased?
Decreasing particle size through recrystallisation or milling
Why is decreasing surface area not always effective?
Decreasing surface area of hydrophobic drugs can cause particles to clump rather than disperse
How can solubility of drugs be increased?
Drugs can be made into the salt
When are drugs 50% ionised?
When pH=pKa
How big is the change in solubility with a pH change of 1?
10-fold change in solubility
Why are ionised drugs less able to be absorbed?
Due to lower lipid solubility
How does the salt form increase ionisation?
Na+ ions buffer the pH to increase it to make the weak acid drug more ionised and increase dissolution
What is logP?
LogP is the partition co-efficient and gives an indication of the ability of a drug to partition lipid membranes
What is the Biopharmaceutics Classification system (BCS)?
Table of permeability vs solubility
What is the ideal logP for oral drugs?
2 - 4.5
What is Class I on the BCS?
Dissolve and absorbed well - Propanalol
What is Class IV on the BCS?
Not soluble in water or lipid - Furosemide
What is passive diffusion?
Occurs with lipophilic molecules along the concentration gradient and does not require energy
What is pinocytosis?
Drug molecule is engulfed and taken through cell membrane
Not common with drug molecules as they are too large
What is Fick’s first law?
dm/dt = PCg
P = permeability constant
Cg = drug concentration in GI fluid
What is active transport?
Active transport involves the use of membrane transporters carrying drug molecules across the GI tract membrane against a concentration gradient which uses ATP
