Oral Drug Delivery Flashcards
What cells are responsible for gastric acid secretion
Parietal cells - acidic environment ph1-3
Ileum characteristics
Ph 5-7 (most drugs absorbed here)
Large sa
Highly vascularised
Drugs may pass through li
Oral drug delivery advantages
ACCEPTABILITY
COMPLIANCE
EASE OF ADMINISTRATION
Oral drug delivery disadvtanges
BIOAVAILABILITY- variable
Certain drugs may be very hydrophobic and may be absorbed better when taken with fatty meal
Proteins will be graded in the stomach
Resukts in toxicity / sub therapeutic issue with drugs
ADVERSE ENVIRONMENT
eg mucus , peristalsis, enzymes, diff ph , gastric emptying - all make it hard for controlled release
DIFFICULTY SWOLLOWING
esp kids and elderly
What is modified release
Modulates the absorption and alters the site of release of drug - time and Space
Common types of mr
Delayed release - constant (plasma conc
Extended release - eg coating may be inert to acidic conditions. Simplifies release and may need one dose instead of two a day
Target release - similar profile to DR . React to conditions at furthest point of git
Advantages of mr
Optimised performance
Less adverse effects
Increase convenance and compliance
Improved efficacy
Mr dosage forms based upon what three release mechanisms
Dissolution
Diffusion
Osmotic
Dissolution mr mechanism
Eg encapuslated dissolution or matrix dissolution
Usually hydrophilic polymers that form a gel layer when in contact with the release media eg HPC, HPMC,
Controls passage of api from dry core to release media
What is drug release in dissolution method influenced by
Solubility
Viscosity
Hydration rate
Molecular weight
Diffusion systems
Drug moves from a more conc to less conc area through membrane. Nature of coating effects drug diffusion
Eg reservoir system (membrane controls drug release )
Most common polymer eg EC
Factors affecting drug diffusion through polymer
Lipophylicity
Mw
Viscosity
Osmotic APPROACH ZFOR MR drugs
Membrane controls the passage of water through media into the tablet
Usually resukts in the release of drug through a small hole eg basic osmotic pump ,, push pull OROS
usually consists of semi perms or membranes like cellulose acetate
In modelling release equation what does each component stand for
Mt/m♾️, k , t , n
Mt/M♾️= fraction of drug release
K= diffusion rate constant
T= time of release
N= release exponient (indicative of release mechanism ).
N=1 modelling release data equation
Drug realase is independent of time (zero order kinetics )
Rate controlling step is therefore polymer relaxation and Erosion
N=o.5
Fickian diffusion is rate controlling step
N between o.5 and 1
Contribution of diffusion and polymer relaxation controlling release kinetics of swellable tablets.
Advantage of osmotic technologies over matrix systems
The ability to deliver drugs with a zero order Kinetics profile independent of external factors.
(Release is constant independent to conc)
What is release rate of osmotic systems dependent on
Osmotic pressure (and solubility if significant )
What to each parameter is the osmotic equation mean
Osmotic e
What does osmotic layer in push pull system usually consist of
Highly swellable polymer (eg High MW PEO) and osmogen (eg nacl)
Advantages of push pull systems
HPI
release rate Independant of hydrodynamics
Release a rate independentcof ph
In vitro and in vivo correlation
Why is release rate independent of hydrodynamics important
In vivo hydrodynamics difficult to create
As recreating gastric hydrodynamics v difficult
Hydrodynamics change in response to food , difficult to mimic In vitro
Why is release rate in OROS independtant of hydrodynamics
With these systems TSH release rate is dependant on the influx of water which is controlled by the osmotic pressure and properties of the coating (i.e permeability and thickness)
So rate of stirring and the differnce of hydrodynamics between fast and fed state will not alter drug release rate
Disadvtages of push pull systems
MIDD
Complex manufacturing process
Local irritation and risk of infection
Drug dumping
Patient distrust
Why are push pull systems difficult to manufacture
Limited selection of excipients and polymers for the membrane and tablet core available
Bilayer tablets require a bilayer press which is expensive
Insoluble, permeable membrane required so requires sue of non aqueous solvent during coating
Laser drilling required following tablet coating (expensive and difficult to access)
Drug loading limited - ~25% of total tabket weight
Reasons for ph sensitive coatings and example s
Drug may irritate the gastric mucus membrane eg NSAIDS
drug may be particularly sensitive to the acidic environment eg PPIS
Drug may need to target a particular section of GIT eg colon specific therapy wg 5-ASA for colitis
Example of enteric polymer names
PVAP (polyvinyl Acetate Phthalate)
HPMCAS (hydroxypropylmethylcellulose acetate succinate)
Eudragit polymers
Factors affecting dissolution in EC formulations
COATING
polymer used
Coating thickness - thicker coating can affect dissolution rate , this can be controlled
Gi tract tract sit and ph- this cannot be controlled
TABLET CORE
Physiochemical properties of api ( water solubility, particle size, ionisation etc)
Excipients combination (is disintergrants , wetting agents -i.e surfactants so that when water comes into contact with the drug it will dissolve quicker )
Processing factors eg compression force (compression high , tabket v hard, dissolution slow)
What does gastric emptying time of tablets in fasted state range from
60-160 mins
What dosage form has less variablitkty in gi transit
Pellets and multi unit dosage forms empty with less variability - gastric emptying times in both the fed and fasted state for pellets are similar they also present les drug dumping , particularly important for dosage forms where dose is hugh
Reduces toxicity and local irritation
Defor oral delivery of macromolecules
SOMA and LUMI
