Oral Drug Delivery

oral route

when a dosage form is adminstered by mouth and intended to be absorbed in the GI tract (small intestines)

Esophagus

- pH 5-6

- LITTLE fluid and drug dissolution

Esophagus transition time

<10 sec for liquids, 10 - 14 sec for solids

Stomach

- typical site of drug dissolution

- mixing is intense

- low pH favors dissolution of weak base drugs

Stomach pH

- Fasted State = 1.5 - 2.5

- Eating State = 4.5 - 5.8

- decreases to <3 1 hr after eating

Small intestine 

- composed of the duodenum, jejunum, and ileum

- use of passive diffusion and transporters/efflux pumps for some drugs

Duodenum and Upper Jejunum

- MAJOR drug absorption sites

- pH = 5 - 6.5

- HIGH SA due to microvilli/villi and folds

- HIGH perfusion = removes absorbed drug

Illeum

- pH = 7 - 8

- LESS drug absorption due to less SA

- can contribute to weak base absorption

- MAJOR active absorption of Vitamin B12

Colon

- lacks villi = ↓ SA

- less blood flow

- LIMITED absorption for most drugs

gastric emptying time (GET) 

- can DELAY onset of action (high fat meals and anticholinergic drugs)

- liquids and small particles are emptied FASTER

- carbs = SPEED emptying time

Intestinal Motility

increase motility can DECREASE residence time and drug absorption

gastrointestinal perfusion

- requires removal by capillaries/lymphatics is required

- maintains [gradient]

- GI tract receives >25% of cardiac output (increased w/ meals)

- REDUCED perfusion = ↓ bioavailability

Food effects

- must be examined during drug development

- can decrease, increase, or have no effect 

- affects rate and/or extent of absorption 

food mechanisms of effect

change GI pH, luminal metabolism, or can physically/chemically interact with dosage form or drug

larger

Bioavailability of drug is better in fasted state with a _____ volume of water (8oz or 250mL)

diseases

cause GI changes can affect absorption (i.e., Heart failure, achlorhydria, Chron’s disease, and celiac disease) 

Genetic Variation

inter-individual differences in uptake transporters, efflux pumps, and drug metabolism

anticholinergic drugs

can ↓ gastric acid secretion, slow GET, and motility

antacids

- contain Ca, Mg, Al can complex w/ certain drugs

- ↑ gastric pH = ↓ dissolution of weak bases = ↑ dissolution of weak acids