Oral Drug Delivery

Question 1

Advantages

Answer 1

1) Patient acceptability & compliance
2) Large surface area for absorption
3) Rich blood supply
4) Prolonged retention
5) Possible for zero-order controlled release
6) Inexpensive
7) For local or systemic delivery

Question 2

Disadvantages

Answer 2

1) Variability in patient population
2) Adverse reactions
3) Proteins & peptides cannot be delivered
4) Metabolism & efflux issues

Question 3

Factors effecting systemic absorption & BA

1) Physicochemical properties of the drug

Answer 3

I) Drug pKa, log P, solubility

Question 4

Factors effecting systemic absorption & BA

2) Formulations factors

Answer 4

I) Type of formulation, particle size, surface area, excipients

Question 5

Factors effecting systemic absorption & BA

3) Anatomy and physiology of the drug absorption site

Answer 5

I) Transport routes & mechanisms
II) GI motility
III) pH
IV) Metabolism
V) P-gp efflux
VI) Presence of food
VII) Individual variations

Question 6

Physicochemical properties of the drug

Answer 6

1) pKa -> ionization
2) log P -> 1-3, Lipophilicity
3) Solubility -> drug in solution -> absorption

Question 7

Types of dosage forms used

Answer 7

• Solutions
• Emulsions
• Suspensions
• Powders
• Tablets
• Capsules
• Modified release granules, tablets & capsules

Question 8

Formulation factors affecting oral BA

1) Particle size -> surface area -> dissolution

Answer 8

I) Micronized or microcrystalline drug forms

Question 9

Formulation factors affecting oral BA

2) Excipients

Answer 9

I) Wetting agents/ surfactants
II) Diluents
III) Binders
IV) Disintegrants
V) Lubricants (glycants)

Question 10

Wetting agents/surfactants (Excipients)

Answer 10

1) Help with dissolution by lowering interfacial tension
- Eg. Polysorbate 80
2) Help with absorption of drugs
- Eg. Sodium dodecyl sulfate

Question 11

Diluents (Excipients)

Answer 11

1) To bulk up formulations
2) Lactose, dextrose, sucrose, microcrystalline cellulose
3) Hydrophilic diluents promote
- Create channels in erosion matrix ER products
4) Hydrophobic diluents decrease dissolution rate of drug

Question 12

Binders (Excipients)

Answer 12

I) Bind powders during the granulation processes & help with compression
II) Starch mucilage, gelatin, polyvinylpyrrolidone (PVP)
III) Coat drug particles so binders dissolution can determine drug release rate
i) Soluble binders (gelatin, PVP) -> fast drug dissolution
ii) Slow dissolving binders (starch) -> slow tablet disintegration & delayed drug release

Question 13

Disintegrants (Excipients)

Answer 13

I) Swell in presence of water to burst open tablet

2) Starch & cation exchange resins
3) High swelling disintegrants -> rapid dissolution & higher BA

Question 14

Lubricants (Excipients)

Answer 14

1) To help tablet ejection from machines & improve flow
2) Stearic acid & its Mg & Ca salts widely used
3) Tend to be hydrophobic & retard dissolution
- add lubricant at end, coats everything

Question 15

Saliva

Answer 15

pH 6.5-7.5

Transit time =

Question 16

Stomach

Answer 16

pH 1-3.5
Liquids 8-12 min
Solids 144-277 min

Question 17

Duodenum

Answer 17

pH 5-7
Liquids 2-60min
Solids 2-60min

Question 18

Jejunum & Ileum

Answer 18

pH 6-7.5
Liquids 1-3hr
Solids 1-5hr

Question 19

Colon

Answer 19

pH 5.5-7

Transit time 36-48hr

Question 20

Rectum

Answer 20

pH 7

Question 21

Transport routes & mechanisms

Answer 21

A) Transcellular passive diffusion
B) Paracellular passive diffusion
C) Carrier-mediated transport
D) Transport through transcytosis
E) Efflux transporters

Question 22

Small molecules (

Answer 22

Transcellular diffusion & carrier-mediated transport

Question 23

Larger molecules

Answer 23

Paracellular pathway or endotranscytosis