D. Oral Controlled Release

Question 1

What is the definition of immediate release ?

Answer 1

Releases whole dose immediately or soon after administration

Question 2

What are the two main types of modified released?

Answer 2

Delayed release

Extended release

Question 3

What is the definition of delayed release ?

Answer 3

Released whole dose later e.g. enteric coated aspirin (avoids release in stomach and gastric irritation)

Question 4

What is the definition of extended release?

Answer 4

Release drug slowly over an extended time. this means that plasma concentrations are maintained at therapeutic levels for a prolonged period of time (8-12hrs)

Question 5

What are the benefits of delayed released oral formulation?

Answer 5

• Avoids stomach irritancy
• Minimised drug degradation before reaches absorption site
• Targeting of drug release e.g. ileum or colon
• Taste masking

Question 6

Explain how delayed release membranes work and how they expose the drug further down the GIT rather than the stomach

Answer 6

The drug core is coated with delayed release membrane (dry)

The membrane coating is resistant to stomach acid and therefore the core cannot disintegrate

When the drug is exposed to the pH environment of small intestine (pH 6.8), the coating dissolves

Disintegration and dissolution of the membrane then leads to exposure of drug core, releasing the drug to site of absorption

Question 7

Who does the membrane polymers only dissolve in alkaline pH conditions of the small intestine?

Answer 7

They have free carboxylic acid groups.

At low pH the polymers will be insoluble due to the carboxylic acid being protonated and unionised (stomach)

At high pH the carboxylic acid will be soluble due to the release of the proton from the carboxylic group resulting in it being ionised. The molecule will become negatively charged and much more soluble (intestine)

Question 8

What are the two types of extended released?

Answer 8

Prompt achievement of plasma concentration of drug remains constant value within therapeutic range for satisfactory amount of time

Prompt achievement of plasma concentration of drug and declines at slow rate within the therapeutic range

Question 9

What are the benefits of extended released ?

Answer 9

• Drug plasma concentration maintained in therapeutic range for extended period of time (useful at night in pain control and can improve sleep)
• Avoid breakthrough of symptoms if plasma concentrations decrease below the minimum effective concentration (OA patients)
• Avoids side effects if plasma levels increase
• Reduce total amount of drug that is being administered therefore will reduce amount of systemic side effects
• Reduces dose frequency (for drugs with short half lives)

Question 10

What are the economical advantages for extended release?

Answer 10

Health services
- Sleep through night, fewer side effects, symptoms , doses. Reduction in doctors/nurses time

To pharam company
- New product, extends patent life of ‘old’ drug, higher value product, more “sophisticated’ claims

Question 11

What are the limitations of extended release?

Answer 11

• Physiological factors such as GIT pH, enzyme activity, gastrointestinal transit rates, food and severity of disease can interfere with the control of release and rug absorption
• Overdose due to slow clearance from the body
• Risk of prolonged toxicity if therapeutic index of drug is too narrow
• Rate of transit of ER product along GI tract limits max period of 12 hrs plus length of time absorbed drug exerts its therapeutic effects
• Accidental poisoning e.g. chewing
• Size of tablet/capsule may be large
• Difficult to swallow
• May also be difficult to formulae with low levels of excipient