oral pharmaceutics workshop

Question 1

oral lipophilic drugs premature by which method?

Answer 1

transcellular route

Question 2

what does Ficks law state?

Answer 2

diffusion is proportional to conc of drug

Question 3

when is class 3 BCS eligible for biowaiver?

Answer 3

if very rapidly dissolving

Question 4

when is class 2 BCS eligible for biowaiver?

Answer 4

if weak acids are highly soluble at pH 6.8, plus dissolution

Question 5

when are oral drugs defined as being soluble in BCS?

Answer 5

when the largest dose of drug is soluble in less than 250ml of water of pH range 1-7.5

Question 6

when are oral drugs defined as being permeable in BCS?

Answer 6

when more than 90% of the dose given, is absorbed

Question 7

Why are 40% of NCE poorly soluble?

Answer 7

as discovered through high throughput screening rather than traditional in vitro methods and theres poor

Question 8

what are the issues with poor drug solubility IN VIVO?

Answer 8

• decreased bioavailability
• increased food effects
• increased effect in diseased states esp GIT
• more frequent incomplete release
• higher inter patient variability

Question 9

what are the issues with poor drug solubility in formulation?

Answer 9

• severely limited choice on technologies
• increasingly complex dissolution testing
• limited/poor correlation with in vivo

Question 10

how can you enhance solubility of a class 2 BCS?

Answer 10

salts
surfactants
nanoparticles
self emulsifying systems
(particle size reduction
solid dispersions 
cyclodextrin)

Question 11

how can you enhance permeability of a class 3 BCS?

Answer 11

self emulsifying systems
(absorption enhancing excipients
efflux transport inhibitors)

Question 12

how can you enhance solubility of a class 4 BCS?

Answer 12

salts
surfactants
nanoparticles 
self emulsifying systems
(pro drugs
co-solvents 
lyophilisation)

Question 13

how do co-solvents help solubility?

Answer 13

prevent precipitation

Question 14

how can you reduce particle size? (to microns e.g.)

Answer 14

1. recrystallisation - by adding solvents and anti-solvents

2. conventional comminution and spray drying - mechanical stress

Question 15

how does reducing particle size enhance solubility?

Answer 15

larger SA
reduced diffusion thickness
increases saturation solubility

Question 16

give examples of drugs which consist of nanoparticles?

Answer 16

ibuprofen
naproxen
loperamide

Question 17

how are nanoparticles produced?

Answer 17

1. micro-milling
2. piston gap - hy hydrodynamic cavitation
3. SCFs

Question 18

what are examples of SCFs?

Answer 18

co2

water

Question 19

SCFs are highly compressible, so what?

Answer 19

means a slight change in temp/pressure will significantly affect the drugs density and mass transport

Question 20

what is a self emulsifying system?

Answer 20

where drug is in a liquid form (to improve solubility) due to addition of co-solvents, surfactants, TGs
the liquid interacts with the gelatine shell of the SGC by either dehydration through the shell or migration into the shell

Question 21

why does SES avoid first pass?

Answer 21

1. the lipids in the drug stimulate release of biliary lipids
   this generates micelles
2. the micelles break down the lipids by lipase enzyme
3. broken down product is packaged into lipoproteins called chylomicrons
4. these enter the circulation via lacteals (lymphatic system, not blood capillary network)and end up in systemic circulation

Question 22

how do you prepare a SES?

Answer 22

incorporate drug into an oil-surfactant mix, until a clear solution is made which is filled into soft capsule (or hard in suspension dried to a powder)

Question 23

give examples of drugs which are SES?

Answer 23

ritonavir

ciclosporin