Oral Delivery of Immediate Release Dosage Forms

Question 1

Immediate Release Def

Answer 1

Rapid drug liberation from dosage form for dissolution and absorption. Fast acting, short term. (drug can only be absorbed as solution). Risks toxic concentrations

Question 2

Solid Dosage Forms

Answer 2

Tablets, capsules, orally disintegrating tablets

Question 3

Liquid Dosage Forms

Answer 3

Solutions, suspensions and emulsions

Question 4

Benefits of oral dosage Forms

Answer 4

easy to admin, high patient acceptability, very stable and can be used to treat diseases in the GIT

Question 5

Why is pH an important consideration

Answer 5

Different regions of GIT have different physiological pHs and stomach has different pH whether in fed/fasted state (fasted is more acididc then fed)

Question 6

Advantages and disadvantages of a liquid/small particle based dosage form

Answer 6

Rapidly emptied from stomach. Less stable then capsules/ tablets (more prone to ionisation) and has no coating

Question 7

LAD in Stomach

Answer 7

Gastric fluids can increase the rate of dissolution. Can decrease/ increase absorption dependent on drug pKa and whther acidic/alkaline. Little drug absorption happens in stomach (all acidic)

Question 8

Factors Increasing Gastric Emptying Rate

Answer 8

Fasting state, low viscosity of contents, high pH, iso-osmatic contents, lower calories and lower fat content

Question 9

Factors Decreasing Rate of gastric emptying

Answer 9

Fed state, lower pH, higher viscosity of contents, contents hyper/hypo-osmatic, higher calories and higher fat

Question 10

Substances that slow rate of gastric emptying (order of increasing)

Answer 10

carbohydrates < protein < fats. Fats produce bile which reduces gastric emptying

Question 11

Effects of drugs on gastric emptying

Answer 11

Drugs that raise pH of stomach contents decrease breakdown and absorption of drugs

Question 12

Fasting State effects on motility

Answer 12

Migrating myoelectric complex. Regular muscle contractions push food to colon. Undissolved dosage forms will be pushed down gut (in 2 hours)

Question 13

Fed State effects on presence of food

Answer 13

Motions are churning over propulsion (segmental and peristaltic). Physically breaks down food. Solid formulation are stuck in for longer

Question 14

Small Intestine Features

Answer 14

3 parts: ileum ,duodenum and jejunum. Chyme mixed with digestive enzymes enabling digestion and absorption. Large surface area for absorption. Single epithelial layer for batter absorption

Question 15

Duodenum Outline

Answer 15

Most permeable epithelium. Transport nutrients. Short in length and rapid in transit. Drug absorption is low in region (due to how transit’s relationship to absorption)

Question 16

Relationship between transit rate, absorption rate and amount absorbed

Answer 16

If fast transit rate isn’t compensated for by a fast absorption rate = a low amount absorbed. When transit time is slow and absorption rate is fast = a lot absorbed

Question 17

How food can decrease drug absorbed

Answer 17

Food can bind to drug (eg chelating), viscosity acts as a physical barrier and food may compete with food for absorption

Question 18

How food can increased drug absorption

Answer 18

Increase bioavailability (saturating 1st pass metabolism) and inhibition of drug metabolising enzymes (eg grapefruit and CYP 3A4)

Question 19

Zollinger-Ellison Syndrome Influence on drug absorption

Answer 19

Gastric pH is decreased, decreasing amount of acid absorbed, increasing amount of drug degraded

Question 20

Ulceration Influence on Drug Absorption

Answer 20

Ulcers increase gastric emptying (decreasing amount absorbed) and can decrease duodenal motility

Question 21

Diarrhea effects on drug absorption

Answer 21

Increased rate of transit = decreased drug absorption

Question 22

Vomiting effects on drug absorption

Answer 22

Drug removed from system without being absorbed

Question 23

Effects of antacids on drug absorption

Answer 23

Antacids can chelate drugs and alteration of pH decreases amount absorbed

Question 24

What determines whether it’s orally bioavailable (can be substrates for transporters in the small intestine)

Answer 24

Lipkin’s Rule of 5 (min 3 factors): MW < 500, Log P <5, H bonds <5 and H acceptors <10

Question 25

How can you compensate for poor solubility and permeability

Answer 25

Salt formulation (electrolyte), particle size reduction (large surface area), prodrug formation (prodrug is more permeable due to esterfication of OH groups), cosolvent use and emulsification/surfactants (stabilise interfacial tension)

Question 26

Fast dissolution of tablets

Answer 26

Tablet disintegrate to coarse particles disintegrate to fine particles to drug solution

Question 27

Intermediate dissolution outline

Answer 27

tablet to coarse particle to drug solution

Question 27

Slow dissolution Outline

Answer 27

Tablet to drug solution

Question 28

Hard Capsule

Answer 28

Powder formulation dissolves after dissolution of shell

Question 29

Soft Capsule Outline

Answer 29

Drug in small volume of liquid solvent with dissolution of capsule shell

Question 30

Release of dosage forms

Answer 30

Mastication, bicarbonate dissolves drug, orally-disintegrating tablets break down rapidly in mouth

Question 31

Palatability Enhancers Excipients

Answer 31

Glucose, sorbitol, viscosity enhancers (polysaccharides)

Question 32

Stability Enhancer Excipients

Answer 32

Cosolvents, suspending agents, lyophilised powder

Question 33

Preservation Excipients

Answer 33

Antimicrobial perservatives

Question 34

2 Ways of Drug Being Removed From Systemic Circulation

Answer 34

Liver (1st pass metabolism) and entrocyte (p-glycoproteins efflux). Reduces bioavalibility