Oral drug delivery

3 main factors influencing oral bioavailability

Physiochemical properties of the drug and drug delivery system (drug release pattern, solubility, permeability)

Biological factors (physiology of GIT, biochemical variance)

Effects of food and other drugs

Oral drug delivery systems release from fastest to slowest

Oral solution (drug is already dissolved, but precipitation may occur in GIT - ethanol, glycerol)

Dispersion (emulsion or suspension)

Capsules

Tablets

Film coated tablets/granules/beads

Modified or controlled release

Noyes-Whitney equation

A = surface area

D = diffusion coefficient

h = diffusion layer thickness

Cs = solubility

C (Ct) = concentration of the drug at time t

For oral drug delivery, a drug substance is classified as highly soluble if the highest single therapeutic dose is completely soluble in ____mL or less.

250

The solubility of a drug substance should be studied over what pH range?

1.2 - 6.8 at body temperature (37 degrees celsius)

Reason for micronization

Increase the surface area, enhance solubility, and improve bioavailability. Used for BCS class II and IV to increase solubility.

Most micronized formulations (are/are not) interchangeable between doses

are not

Partition coefficient equation

log P = log of solute (octanol)/ unionized solute (water)

distribution coefficient equation and definition

Log D = log of solute (octanol)/ ionized and unionized solute (water)

Ratio of the concentrations of a drug in a mixture of two immiscible liquids at equilibrium (oil/water)

Measure of lipophilicity

High permeability can be concluded when the absolute bioavailability is over what percentage?

85

BCS class I

High permeability and high solubility

BCS class II

high permeability and low solubility

BCS class III

high solubility and low permeability

BCS class IV

low permeability and low solubility

What type of molecules have a fast absorption rate (high permeability)

Non polar groups, like estrogen

What type of molecules have a slow absorption rate (low permeability)

Small polar groups, like glycerol, and acetic acid at pH 1.5 (not ionized)

What type of molecules are not permeable to the membrane?

Large polar or charged molecules, like sucrose or acetic acid at pH 7 (ionized)

Dysphagia or odynophagia

difficulty swallowing or painful swallowing

Pill induced esophagitis

medications that irritate the esophageal mucosa (antibiotics, NSAIDs, bisphosphonates, chemo agents, KCl tablets)

patients who can’t be in an upright position for some time

Counseling points to prevent pill induced esophagitis

take meds with a full glass of water

remain upright for at least 30 minutes after taking meds

avoid lying down after taking pills

swallow pills properly without crushing or chewing them

Digestive (fed) phase of gastric emptying

Cephalic phase (when you prepare/see/smell to eat food, 20% of secretion)

Gastric phase - the pylorus allows only the passage of liquid and small particles (less than 2mm)

What kinds of drugs can and cannot pass through the stomach during the digestive (fed) phase?

Enteric coated tablets will stay in the stomach for a very long time until food is digested.

Microgranules or beads are not held back in the stomach and can diffuse through the stomach lining.

Interdigestive (fasted) phase of gastric emptying

Migrating motor complex where food is digested.

Migrating motor complex phase 1

45-60 minutes, no activity (rare contractions)