Oral Delivery

Question 1

What is the maximum amount of fluid the stomach can hold?

Answer 1

1 L

Question 2

What cells release hydrochloric acid and what is the pH of the stomach?

Answer 2

Parietal cells at pH one to 3

Question 3

What is the pH of the duodenum?

Answer 3

5 to 7

Question 4

what is the pH of the ileum?

Answer 4

7 to 8

Question 5

What are the advantages of oral drug delivery?

Answer 5

Better patient acceptability
Better patient compliance
Ease of administration

Question 6

What are the disadvantages of oral drug delivery?

Answer 6

Bioavailability variability – depends on pH
The adverse environment of the GI tract
Difficulty swallowing

Question 7

What is modified release and what is it split into?

Answer 7

The ability to modulate absorption and the site of release of a drug
Delayed release
Extended release
Targeted release

Question 8

What are the benefits of modified release delivery?

Answer 8

Increased efficacy- don’t need multiple doses
Reduced adverse reactions due to no peaks in concentration
Increased patient convenience and compliance

Question 9

What are the three release mechanisms in modified release?

Answer 9

Diffusion- reservoir (nonporous/microporous) or monolithic (non-porous/microporous)
Dissolution- encapsulated or matrix
Osmotic-osmotic pump or push – pull OROS

Question 10

what are examples of polymers used in dissolution mechanisms?

Answer 10

HPMC (hypromellose), HPC
These polymers eventually turn into solution

Question 11

And what type of release is hypromellose (HPMC) used for?

Answer 11

Extended

Question 12

What are general characteristics of extended release polymers?

Answer 12

Hydrophilic
Robust and flexible and easy to make
Water soluble and gel forming and/or swellable

Question 13

How do you alter the viscosity of HPMC polymer?

Answer 13

Alter the functional grips (methoxy/hydroxypropyl)

Question 14

In what forms is hypromellose available?

Answer 14

Methocel E and k

Question 15

How do HPMC matrixes work?

Answer 15

Drug and polymer are in the tablet, fluid enters, hydro gel forms on surface which controls fluid in and drug out

Question 16

Can you release a drug from a tablet for 2 to 3 days?

Answer 16

No, the GI eliminates

Question 17

What happens if you have a high concentration of polymer/high molecular weight of polymer?

Answer 17

Increased viscosity = decreased disolution = decreased drug release

Question 18

How is drug release controlled in extended release formulations

Answer 18

The gel layer- the more viscous the polymer, by increasing molecular weight or polymer concentration, the last distillation and the last drug race

Question 19

What is the equation for measuring the fraction of drug release over a given time (in vitro)

Answer 19

Mt/m= kt^n

Mt/m= fraction of drug released
K= diffusion rate constant
T= time of release
N= release exponent – release mechanism

Question 20

Delayed release formulations need to be enteric coated, what are examples of these coatings and how are they applied to the tablet?

Answer 20

PVAP-polyvinyl acetate
HPMCAS- hydroxy propyl – methyl cellulose acetate
Coatings are sprayed onto tablets surface

Question 21

How do enteric coatings work?

Answer 21

They are PH sensitive and are resistant to the acidic gastric pH and dissolve an intestine

Question 22

Why do we need delayed release formulations?

Answer 22

Protect from gastric mucosa irritation (NSAIDs)
Protect drug from gastric environment (PPI’s)
Drug to particular section of the GI tract (5ASA)

Question 23

How can you alter polyvinyl acetates drug delivery site?

Answer 23

Add more acid grips to the backbone

Question 24

What order of kinetics is osmotic technology?

Answer 24

Zero order – constant release

Question 25

What is the maximum length of delivery by osmotic technology?

Answer 25

12 hours because GI excretes

Question 26

What is the overall mechanism of osmotic technology?

Answer 26

The osmotic agent (salt) attracts water
Semi permeable membrane let water in but not drug out
Drug leaves through orifice (hole)- expensive laser

Question 27

What polymers used in osmotic technology?

Answer 27

Cellulose acetate -plastic coating

Question 28

What is the equation for osmotic drug release?

Answer 28

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

Question 29

What factors affect drug dissolution in enteric coated formulations?

Answer 29

Coating thickness
Polymer used
GI transit and pH
Physio chemical properties of the active pharmaceutical ingredient
Excipient combination

Question 30

What two types of osmotic systems are there?

Answer 30

Elementary osmotic pump (EOP)
Push pull osmotic system

Question 31

What is the elementary osmotic pump?

Answer 31

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

Question 32

What is the push - pull osmotic system?

Answer 32

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

Question 33

Why are use a push pull osmotic delivery system?

Answer 33

For hydrophobic drugs
Or higher drug loading

Question 34

Why can’t you cut a push pull osmotic system in half?

Answer 34

Increased side effects due to the high drug loading dose

Question 35

What are the advantages of push pull osmotic system?

Answer 35

Better compliance – less dosing
Less side effects (no peaks)
Release is not pH dependent
Can add aesthetic coatings

Question 36

What are the disadvantages of PP osmotic systems?

Answer 36

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