Oral Drug Delivery 1 Flashcards
What is the most frequently used administration route and why
Oral - simplest, most convenient and safest route
In what ways is the stomach not designed for absorption
Variable volume
Hydrochloride acid creates an acidic environment (most drugs are weak acids)
Advantanges of oral route
ACE
Acceptability
Compliance
Ease of administration
Disadvantages of oral route
BAD
Bioavailability varies
Adverse environment in the stomach
Difficulties swallowing
How is the stomach a bad environment for absorption?
Acidic environment
Gastric emptying
Bioavailability varies with changing conditions in the stomach
What is a modified release product
MR products modulate absorption by altering the site of release of the drug
Drug only releases when it reaches a targeted section of the GI tract
Therapeutic benefits of modified release products
Improved efficacy
Increases patient convenience
Reduce adverse effects
Optimises drug performance
Objective of a MR product
The objective of an MR product is to alter the drug input (in time or space) in the intestinal lumen
3 common ways of MR
TED
Targeted release
Extended release
Delayed release
3 release mechanism offered by oral MR products (physical mechanisms) & examples of each
Diffusion - reservoir system
Dissolution - matrix dissolution system
Osmotic - basic osmotic pump
Polymers used in 3 release mechanisms
Dissolution - HPC & HPMC
Diffusion - EC
Osmotic - cellulose acetate (semi-permeable membrane)
Polymers for extended release systems
Hydrophilic matrices are used for ER
Polymers used are water soluble and gel forming
Mechanism for hydrophilic polymers in ER systems
Matrix makes contact with intestinal fluid
Hydrophilic polymer on surface of matrix hydrates to form a gel layer
Gel layer controls fluid entry and controls release
What is hypromellose
Hypromellose is a a water-soluble, hydrophilic polymer commonly used in ER preparations
It goes by the name methocel E & K
Advantages to using hypromellose
Rapid and uniform formation of gel
Good physical properties
Low cost
Ease of manufacture
Steps in drug release from a matrix tablet (4 steps)
Initial wetting - to form the gel layer
Expansion of gel layer - water permeates tablet increasing the thickness of the gel layer
Tablet erosion - outer layer becomes fully hydrated, then dissolves in gastric fluid
Soluble drugs diffuse through gel layer; Insoluble drugs are release by erosion
What equation is used to model release date
Korsmeyer-Peppas equation
Mt/Mo = kt^n
N - release exponent
K - diffusion rate constant
T - time of release
Mt/Mo - fraction of drug release
How do different n (release exponent) values affect release data modelling
n = 1 - Drug release is independent of time (zero order kinetics)
Rate controlling step is polymer erosion
n = 0.5 - Fickian diffusion is the rate controlling mechanism (ficks law)
n = 0.5 - 1 - Both diffusion & polymer erosion control release kinetics
