Pharmaceutics - Excipients for Matrix Tablets

Question 1

In the biopharmaceutical classification systems (BCS), describe the solubility and permeability of class 1 drugs?

Answer 1

high sol and high perm

Question 2

In the biopharmaceutical classification systems (BCS), describe the solubility and permeability of class 2 drugs?

Answer 2

low sol and high perm

Question 3

In the biopharmaceutical classification systems (BCS), describe the solubility and permeability of class 3 drugs?

Answer 3

high sol and low perm

Question 4

In the biopharmaceutical classification systems (BCS), describe the solubility and permeability of class 4 drugs?

Answer 4

low sol and low perm

Question 5

what factors affect drug bioavailability?

Answer 5

1. Drug release: Drug must be released into and dissolve in GI fluids to be absorbed across GI mucosa.
2. Drug solubility: Low drug solubility in GI fluids associated with slow drug dissolution and thus absorption.
3. GI permeability: Low GI mucosal permeability associated with slow drug diffusion across GI mucosa.

Question 6

what is a hydrophilic matrix tablet?

Answer 6

• an extended release formulation containing gel-forming polymers
• usually produced by dry granulation or direct compression

Question 7

How does a hydrophilic matrix tablet work?

Answer 7

• uses a combination of drug diffusion and matrix erosion
• the polymer matrix swell upon hydration, then the tablet gels from outside in.
• This gel forms a diffusion barrier
• the soluble matrix then erodes slowly and the drug diffuses out

Question 8

Give examples of matrix formers?

Answer 8

1. hydroxypropyl cellulose
2. Hydroxypropyl methylcellulose
3. polyethylene oxide

Question 9

what factors reduce the rate of release of hydrophilic matrix tablets?

Answer 9

Higher:

1. molecular weight
2. proportion of polymer content
3. degree of hydrophobic substitutions
4. degree of polymer cross-linking

Question 10

what makes polyethylene oxide a more useful hydrophilic matrix?

Answer 10

its higher molecular weight

Question 11

what is an insoluble matrix tablet?

Answer 11

an extended release formulation containing porous insoluble polymer matrix

Question 12

how does an insoluble matrix tablet work?

Answer 12

• Diffusion-based system (polymer matrix remains intact).
• Drug incorporated in pores.
• As water enters pores, drug dissolves and diffuses out
  through water-filled pores.
• First-order drug release.
• Insoluble polymer shell egested.

Question 13

what is a monolithic tablet?

Answer 13

• a single-unit tablet with an IR core and ER coating.

- Rate of drug release is dependent on the coating

Question 14

what is a multiple-unit tablet?

Answer 14

• a MR coated pellet in a IR tablet matrix.

- rate of drug release dependent on coating

Question 15

what are the differences between multiple-unit tablets and single-unit tablets?

Answer 15

• lower risk of dose dumping in multiple-unit than in single-unit tablets
• multiple-unit tends to use pellets rather than tablets due to less susceptibility to gastric entrapment

Question 16

what are the two ways membrane-controlled ER tablets work?

Answer 16

1. Membrane hydrates and swells, opening
   diffusion pathways.
2. Soluble polymer plugs (e.g. plasticiser) in insoluble coating dissolves, opening pores. Water diffuses
   in and drug diffuses out through pores in membrane

Question 17

what is an osmotic pump system?

Answer 17

a semi-permeable outer membrane with an orifice in it (a soluble polymer plug/laser-drilled)

Question 18

how does an osmotic pump system work?

Answer 18

• Water enters dosage form by osmosis through semi-permeable membrane.
• Increased osmotic pressure forces solubilised or suspended drug out through orifice.
• Optional: Push compartment swells, pushing drug out
  through orifice.
• Zero- or first-order release

Question 19

what is a gastro-retentive system?

Answer 19

-when the ER formulation evades (avoids) the gastric emptying so drug is retained in the stomach either for treating gastric conditions or due to poor intestinal absorption

Question 20

How does the gastro-retentive system work?

Answer 20

-if the drug has a high density-it sinks to pyloric region
-if the drug is effervescent then the system generates and entraps CO2, causing
dosage form to float in gastric fluid
-if the drug is magnetic, then it’s retained with an external magnet
-if the drug swells, it enlarges upon hydration so becomes too large to pass through the pylorus
-if the drug is mucoadhesive, it adheres to the gastric lining