Factors effecting GIT absorbtion Flashcards
For small molecule drugs, the X is the major site of absorption, regardless of the dominant ionization state (if applicable) of the molecule
For small molecule drugs, the small intestine is the major site of absorption, regardless of the dominant ionization state (if applicable) of the molecule
The stomach IS OR IS NOT a significant site of absorption
The large intestine IS OR IS NOT a significant site of absorption
The stomach is not a significant site of absorption
The large intestine is not a significant site of absorption
- Granules- ARE OR ARENT ABSORBED absorbed
- Particles ARE OR ARENT absorbed
- Molecules in solution
Are absorbed
Indeed, the API has to be in solution for it to be absorbed
- Granules - Are not absorbed
- Particles - Are not absorbed
- Molecules in solution - Are absorbed
Indeed, the API has to be in solution for it to be absorbed
Four physical factors which effect solubility and dissolution
- Particle size/ SA
- Physical form (amorphouse dissolves faster due to disordered structure and less structural stability than crystaline)
- Hydration state of physical form - hydrated compounds have a more open structure, and lower lattice energy
- Salt formation - it enhances solubility making it more polar so dissociates more readily in water
Define solubility and dissolution rate
- Solubility: how much of an API will dissolve in a given volume of solvent at a given temperature
- Dissolution rate: how fast does an API get into solution in a given volume of solvent at a given temperature
- Although distinct, in general higher solubility leads to faster dissolution
Small particles = X surface area = X dissolution
Small particles = larger surface area = faster dissolution
Why are salts so commonly used in drugs
- E.g. metformin hydrochloride, salbutamol sulfate, atorvastatin clacium
- Salt formation increases ionisation and polarity, because ionic bonds interacts more with water
- Dissolves faster and API has to be in solution to be absorbed
- Salt is an ionised form of the drug
Why do we prefer drugs to be weak acids or weak bases in the GIT
- The stomach is pH 1-3 while intestine pH 6-8. Weak acids and bases can exploit these to maximise absorption
- Weak acids: exist in non ionised form in the stomach. So they pass through membranes faster
- Weak bases: tend to be non ionised in the intestine. So absorbed more here
Why are more drugs weak bases than weak acids
- Weak bases: tend to be non ionised in the intestine. So absorbed more here
- Intestine has a larger surface area, so is the primary site of absorption
- Because stomach has a small SA regardless of ionisation state very little absorption occurs
- Molecule needs to be in solution to be absorbed
- Molecule needs to be unionised to be absorbed
- But….
- Molecule needs to be in solution to be absorbed
- Molecule needs to be unionised to be absorbed
- But….
- Molecule might not be that soluble when unionised
- Molecule might be unionised in the stomach, but not absorbed because of small surface area
- Molecule might be ionised in the small intestine, but is still absorbed due to large surface area & equilibrium
- Don’t think in absolutes ! (e.g. with Lipinski)
What is an ‘acid labile’ drug
- Low pH, ca. 1-3
- Many drugs are “acid labile” i.e. they break down in acidic conditions, losing their activity as a result e.g.
How does ‘enteric coating’ work
- It is a special acid insoluble polymer coating the drug
- It protects the API in acidic environments like the stomach - and protects stomach from API
- The polymer only dissolves in higher pH environments of the small intestine
- Dosage form stays intact until it has passed through the stomach
- Due to more absorption/larger SA in SI
pH of the large intestine
- pH 6.5-7.5
- Not a major site for drug absorption
Name a drug that targets large intestine
- Aminosalicytes for IBD
- Formulation needs to ensure API reaches colon intact
Describe how mesalazine is designed for its function
- Targets large intestine for anti-inflammatory action in IBD
- Has a ‘eudragit’ coating - dissolves at pHs > 7
