Oral Delivery Flashcards
What is the maximum amount of fluid the stomach can hold?
1 L
What cells release hydrochloric acid and what is the pH of the stomach?
Parietal cells at pH one to 3
What is the pH of the duodenum?
5 to 7
what is the pH of the ileum?
7 to 8
What are the advantages of oral drug delivery?
Better patient acceptability
Better patient compliance
Ease of administration
What are the disadvantages of oral drug delivery?
Bioavailability variability – depends on pH
The adverse environment of the GI tract
Difficulty swallowing
What is modified release and what is it split into?
The ability to modulate absorption and the site of release of a drug
Delayed release
Extended release
Targeted release
What are the benefits of modified release delivery?
Increased efficacy- don’t need multiple doses
Reduced adverse reactions due to no peaks in concentration
Increased patient convenience and compliance
What are the three release mechanisms in modified release?
Diffusion- reservoir (nonporous/microporous) or monolithic (non-porous/microporous)
Dissolution- encapsulated or matrix
Osmotic-osmotic pump or push – pull OROS
what are examples of polymers used in dissolution mechanisms?
HPMC (hypromellose), HPC
These polymers eventually turn into solution
And what type of release is hypromellose (HPMC) used for?
Extended
What are general characteristics of extended release polymers?
Hydrophilic
Robust and flexible and easy to make
Water soluble and gel forming and/or swellable
How do you alter the viscosity of HPMC polymer?
Alter the functional grips (methoxy/hydroxypropyl)
In what forms is hypromellose available?
Methocel E and k
How do HPMC matrixes work?
Drug and polymer are in the tablet, fluid enters, hydro gel forms on surface which controls fluid in and drug out
Can you release a drug from a tablet for 2 to 3 days?
No, the GI eliminates
What happens if you have a high concentration of polymer/high molecular weight of polymer?
Increased viscosity = decreased disolution = decreased drug release
How is drug release controlled in extended release formulations
The gel layer- the more viscous the polymer, by increasing molecular weight or polymer concentration, the last distillation and the last drug race
What is the equation for measuring the fraction of drug release over a given time (in vitro)
Mt/m= kt^n
Mt/m= fraction of drug released
K= diffusion rate constant
T= time of release
N= release exponent – release mechanism
Delayed release formulations need to be enteric coated, what are examples of these coatings and how are they applied to the tablet?
PVAP-polyvinyl acetate
HPMCAS- hydroxy propyl – methyl cellulose acetate
Coatings are sprayed onto tablets surface
How do enteric coatings work?
They are PH sensitive and are resistant to the acidic gastric pH and dissolve an intestine
Why do we need delayed release formulations?
Protect from gastric mucosa irritation (NSAIDs)
Protect drug from gastric environment (PPI’s)
Drug to particular section of the GI tract (5ASA)
How can you alter polyvinyl acetates drug delivery site?
Add more acid grips to the backbone
What order of kinetics is osmotic technology?
Zero order – constant release
What is the maximum length of delivery by osmotic technology?
12 hours because GI excretes
What is the overall mechanism of osmotic technology?
The osmotic agent (salt) attracts water
Semi permeable membrane let water in but not drug out
Drug leaves through orifice (hole)- expensive laser
What polymers used in osmotic technology?
Cellulose acetate -plastic coating
What is the equation for osmotic drug release?
Dm/dt= kA/h x 🔼pi[S]
Dm/dt= amount of drug released
🔼pi = osmotic pressure- can be increased by increasing salt content
A= membrane area
K= permeability coefficient
H= membrane thickness
[S]= drug solubility
What factors affect drug dissolution in enteric coated formulations?
Coating thickness
Polymer used
GI transit and pH
Physio chemical properties of the active pharmaceutical ingredient
Excipient combination
What two types of osmotic systems are there?
Elementary osmotic pump (EOP)
Push pull osmotic system
What is the elementary osmotic pump?
One chamber single layer compressed tablet
Semi permeable polymer coating (cellulose acetate)
Orifice
Water is drawn through the membrane, drug released through orifice as solution
What is the push - pull osmotic system?
Two chambers
Bottom chamber = swellable polymer and osmotic agent salt
Top layer is drug
Water is drawn in through semi permeable membrane into bottom layer which swells and pushes drug out through orifice
Why are use a push pull osmotic delivery system?
For hydrophobic drugs
Or higher drug loading
Why can’t you cut a push pull osmotic system in half?
Increased side effects due to the high drug loading dose
What are the advantages of push pull osmotic system?
Better compliance – less dosing
Less side effects (no peaks)
Release is not pH dependent
Can add aesthetic coatings
What are the disadvantages of PP osmotic systems?
Complex manufacturing
Laser drill expensive for orifice
Limited drug loading due to Osmo agent
Local irritation if drug gets stuck
If tablet breaks – drug dumping
