Oral drug delivery Flashcards
what are the advantages of oral drug delivery
-patient convenience as it isn’t invasive , so higher compliance
-easily manufactured and is cheap
-high surface area of tablet so is available for absorption
what are the oral delivery systems
Sustained release: releases drugs at a slower rate to maintain drug levels in body for longer
Extended release: releases drug over an extended period of time in a more controlled manner to allow once daily dosing
factors that affect oral drug bioavailability
-low solubility of the drugs means it will take time to dissolve and then DISSOLUTION will be the rate limiting step (slowest step in the process)
-RLS could also be the PERMEATION across intestinal membrane (small intestine to reach circulation)
-RLS, GASTRIC EMPTYING meaning the rate at which the stomach empties the drug into small intestine
-METOBALISATION RATE, body changes the drug so that it can be more easily excreted e.g. in the liver
what is the inner lining/surface of the gastrointestinal tract that is in direct contact with the food passing through the digestive system
the luminal surface
what is oral absorption
when a drug is absorbed from the GIT into the bloodstream
explain how GI pH is a barrier for oral absorption
-acidic nature of the stomach can degrade or denature drugs that are especially acid sensitive e.g. pepsin can break them down before they are absorbed
-drugs cannot dissolve well in acidic conditions and they need to dissolve in GIT fluids before being absorbed
which pH is higher, intestinal or gastric/stomach
-intestinal
-neutralisation with bicarbonate secreted by pancreas into small intestine (more alkaline environment for drugs to be more easily absorbed)
a barrier for oral absorption
what is the ionisation status
drugs can exist in the ionised/charged form or non-ionized forms
-uncharged is more lipid-soluble so can cross membrane better and is more easily absorbed
-ionized drugs are less lipid soluble so less easily absorbed
where are weak acid and weak bases better absorbed in
weak bases in the small intestines and weak acids in the stomach
how are luminal enzymes act barrier to oral absorption and given an example
they can break down the drugs before absorption
-pepsin and protease can cause degradation to protein drugs
-ester drugs are susceptible to hydrolysis by esterase enzymes in the lume
how can food act as a barrier to oral absorption
-can alter gastric pH, e.g. making it more acidic
-heavy foods can delay gastric emptying
how do physiological disorders affects oral absorption
-GI disorders e.g. crohn’s disease can lower bioavailability, alter GI pH and destabilise the drug
how does pre systemic metabolism work and how does it act as a barrier of oral absorption
-Also known as first pass metabolism and is the metabolism of a drug before it reaches circulation/bloodstream
1) once the drug passes the intestinal cell membrane it travels to the liver via the hepatic portal system
how does pre systemic metabolism act as a barrier of oral absorption and given an example
-reduces the amount of the active drug
-in the liver, cytochrome P450 can deactivate the drug or make it less active
-propranolol is well absorbed but only 30% is available for systemic circulation due to the first pass effect
-gut wall also contains some metabolic enzymes e.g. CY3A4 to metabolise some drugs
explain step by step the administration of an oral tablet
name 2 physiological (not disorders)) barriers of oral drug absorption and how
1) mucus layer, protective layer of the intestinal lumen. Slows down and traps drug molecules preventing them from being absorbed by epithelial cells (next to bloodstream)
2) unstirred water layer, exists between mucus layer and the epithelial cells where drugs diffuse to epithelial. Lipophilic drugs have trouble dissolving here. Also increasing thickness means slower diffusion
transcellular mechnanism how does the it work
Transcellular: passive and active diffusion and endocytosis
Passive: small, lipophilic drugs. High to low e.g. steroid and sex hormones
Active: uses carrier proteins for transportation e.g. penicillin
Endocytosis: Process of allowing cells to take in substances like drug from environment by engulfing them e.g. phagocytosis. For macromolecules
what is Fick’s first law and what type of mechanism of drug uptake is it related to
passive diffusion
(dC/dt) = DA/h x (Cs-Cb)
-dC/dt = rate of change of concentration (how much drug is begin absorbed)
-D = diffusion coefficient (how easily a drug can be absorbed)
-A= surface area
-h= membrane thickness
-Cs = concentration of the membrane where the drug is
-Cb= concentration of the membrane opposite side to the drug
explain the paracellular mechanism of drug uptake of oral ones
paracellular pathway is the movement of drugs through the spaces between the walls
only for small molecules or ions
what are the mechanisms of drug uptake
-transcellular
-paracellular
what is efflux
drugs are transported out of the cell via efflux transporters e.g. p-glycoprotein. Pumps back into the intestinal lumen, decreasing amount of drug absorbed
