Physiochemical Factors affecting drug absorption Flashcards
pKa drug of the drug
In drug development, the knowledge of pKa is important as it influences the solubility, oral absorption, distribution, and pharmacokinetics of a drug.
Lipid solubility of a drug
Drug absorption by passive diffusion depends on the drug being to partition into GI barrier which is essentially a lipid barrier.
Non ionised form of drug more lipid soluble
pKa, lipid solubility of drug and pH at absorption site dictate absorption characteristics of drug
refer to PPT
Noyes whitney equation
The rate at which drug molecules diffuse across the diffusion layer surrounding a drug particle is considered to control the dissolution process. Under such conditions, dissolution is described quantitively by the Noyes whitney equation.
Refer to PPT
Effective SA of a drug
A reduction in particle size usually results in increases in the rate and extent of drug absorption
in the cases of some drugs, a reduction in particle size and the increased bioavailability was found to be undesirable. Example. resulted in increased incidence of side effects.
Cases in which particle size reduction fails to enhance drug bioavailability
a poorly soluble hydrophobic drug
a drug which does not exhibit dissolution rate limited bioavailability
drugs which are chemically unstable in gastric fluid
Crystal form of a drug
Many drugs can exist in more than one crystalline form. Each crystalline form exhibits different physical properties. Eg. melting point, dissolution rate, aqueous solubility.
Another variation in the crystalline form of drug can occur if the drug is able to associate with solvent molecules to produce crystalline forms known as solvates. When water is solvent, the solvate is a hydrate. The greater the solvation in a crystal, the lower is the solubility and dissolution rate. this may therefore exhibit differences in bioavailability.
Solubility of the drug in the diffusion layer surrounding each drug particle in the GI tract
Weak acidic drugs exhibit poot rates of dissolution in GI fluid since such drugs exhibit low solubilities at such low pH’s.
If the pH in the diffusion layer could be increased, then the solubility of the drug in this layer would increase. Hence the dissolution rate of the weak acidic drug in gastric fluid would increase even though the bulk pH of the GI fluid remained at the normal low pH.
Chemical stability of drugs in the GI fluids.
Poor bioavailability usually results if a drug undergoes extensive acid or enzyme hydrolysis.
due to this some drugs are given via peroral routes ( IV ) in order to increase bioavailability.
