Formulation - Oral Controlled Delivery

Question 1

How does an enteric coating work?

Answer 1

The COOH means they are insoluble in aqueous media at low pH (1-3)
As pH rises, there is a sharp increase in solubility
- > pH 5
Delay and significant variability in onset of activity
- gastric emptying can range from 30 mins to several hours
Good mechanical film properties required to ensure integrity of the coating
Performance should remain unchanged with time of storage

Question 2

How do enteric coated granules work?

Answer 2

Entrapment of granules in a rapidly dissolving hard gelatine capsule or rapidly disintegrating tablet
- eliminates dependence on all or none gastric emptying and ‘dose dumping’ onto intestinal mucosa
- < 1mm pellets or granules empty from the stomach with liquids via closed pyloric sphincter
- small enough to pass through

Question 3

What does the diffusion rate of a drug depend on?

Answer 3

Surface area
Diffusional pathway
Drug concentration
Diffusion coefficient

Question 4

What is a reservoir type diffusion controlled drug?

Answer 4

Tablet or multiparticulate pellet containing drug
- drug does not diffuse in the solid state
- membrane does not swell but liquid diffusing in forms a continuous phase

Question 5

What is the rate of release of a reservoir type diffusion controlled drug determined by?

Answer 5

Type of membrane

Question 6

What are the properties of a polymer membrane in a reservoir type diffusion controlled drug?

Answer 6

Must be intact during the time of release
Should not swell or degrade

Question 7

Give examples of polymers used in reservoir type diffusion controlled drugs

Answer 7

Ethyl cellulose
Acrylic polymers
- Eudragit RL

Question 8

What is the difference between an immediate release tablet and a reservoir type diffusion controlled tablet?

Answer 8

Core is not designed to disintegrate with a MR tablet
- it is designed to dissolve

Question 9

Describe a multiple unit reservoir type tablet

Answer 9

Usually coated pellets - 1mm in a hard gelatine capsule or compressed tablet

Question 10

What are the advantages of a diffusion controlled modified release tablet?

Answer 10

For a multi-unit system, the GI transit is less variable than for the smaller particulates than a single dose larger unit
Less likely to show total dose dumping
Release can be more easily optimised for each drug

Question 11

What are the disadvantages of a diffusion controlled modified release tablet?

Answer 11

Dose-dumping can occur from a single-unit system
Multi-unit systems can be difficult to retain in higher GI
Control of polymer membrane coating and its characterisation can be difficult
Filling multi-unit systems into capsules can be a problem
- static build up

Question 12

Give examples of diffusion controlled monolithic matrix systems

Answer 12

Soluble and hydrophilic colloid matrix
- drug particles dispersed in a soluble matrix
- hydrophilic
- drug becomes available as the matrix
- dissolves
- swells
- or swells and dissolves

Lipid or insoluble polymer matrix
- drug particles dispersed in an insoluble matrix
- drug becomes available as the solvent enters the matrix and dissolves the drug particles
- water makes pathways
- more as more particles dissolve

Question 13

How do diffusion controlled monolithic matrix systems break down?

Answer 13

Surface erosion
- drug is solubilised from the degrading surface
Bulk erosion
- degrades from interior creating more channels for diffusion of drug out
Dissolution of polymer

Question 14

Give examples of excipients used to make a soluble matrix

Answer 14

Give examples of excipients used to make a soluble matrix

Question 15

Give examples of excipients used to make an insoluble matrix

Answer 15

Polyvinylacetate
Ethylcellulose
Waxes

Question 16

What are channelling agents?

Answer 16

Excipients in an insoluble polymer matrix that can used to leach from the formulation leaving tortuous channels
- NaCl
- sugars