Lecture 10

Question 1

Importance of drug delivery

Answer 1

The drug needs to get to the right place at the right time with the required dose/concentration, just be pharmacologically active is not enough.

Question 2

Systemic circulation =

Answer 2

Bloodstream.

Question 3

Characteristics of the mucosa found in the oral cavity

Answer 3

Gingival - gums, keratinised/non polar.
Palatal - roof of mouth, keratinised/non polar.
Buccal - cheek, upper and lower lip, nonkeratinised/polar
Sublingual - frenulum, floor of mouth, nonkeratinised/polar.

Question 4

What is the buccal tissue in comparison to the sublingual tissue ?

Answer 4

The buccal tissue is thicker in comparison and therefore has more cells.

Question 5

What is the major barrier to drug delivery ?

Answer 5

The oral mucosa.

Question 6

The way a drug can travel the oral mucosa ?

Answer 6

Intracellular route - across/through the cells.

Extracellular route - between cells.

Question 7

Where do the drugs end up when they pass through the barriers ?

Answer 7

The drugs end up in the blood supply which is hooked up to the systemic circulation where the drugs will be carried away.

Question 8

Methods of buccal delivery

Answer 8

Sublingual membrane - under the tongue, very fast absorption of drug.
Buccal membrane - from the cheek and lip cavity, slower absorption but more controlled release.

Question 9

Why is there a different in drug absorption between the sublingual and buccal membranes ?

Answer 9

Due to the difference in the thicknesses of the membranes.

Question 10

Buccal delivery systems

Answer 10

Sublingual tablets, lozenges, adhesive tablets, periodontal release systems, chewing gums, buccal patches, mouth rinse, spray, hydrogels.

Question 11

What can affect a drugs ability to be absorbed from the mouth ?

Answer 11

The physiochemical properties of the drug.

Question 12

Basic drugs

Answer 12

Increased pH leads to increased absorption.

Question 13

Acidic drugs

Answer 13

Increased pH leads to decreased absorption.

Question 14

What is the local pH in the mouth ?

Answer 14

5.8-7.6.

Question 15

What is the optimum log P for drugs for the sublingual mouth ?

Answer 15

1.6-3.3.

Question 16

What is pKa ?

Answer 16

The point at which the drug molecule is at 50% ionised and 50% unionised.

Question 17

What happens when things are ionised ?

Answer 17

They become very soluble.

Question 18

Why is there an increase in absorption for basic drugs when there is an increase in pH ?

Answer 18

This is because the basic drugs will be unionised and therefore will be able to diffuse across the lipid membrane.

Question 19

What is the pH patron hypothesis ?

Answer 19

Unionised forms of drug will diffuse across the lipid membrane.

Question 20

What happened when a formulation is applied to a sublingual space ?

Answer 20

The drug will be absorbed from the space and go into the two vein complexes (facial veins) close to the surface where they are drained along with the drugs and goes straight to the heart - the first organ the drugs encounter.

Question 21

Advantages of buccal delivery

Answer 21

Avoids first pass - the drug goes straight the the heart and then around the body whereas GI delivery requires the drug to go through the stomach then liver where this is detox and the drug is processed.
Prolonged delivery.
Unaffected by eating.
Avoids adhesion of the dosage form to the oesophagus.
Can be removed once the desired effect id no longer required.

Question 22

Disadvantages for buccal delivery

Answer 22

Needs to be highly potent.
Needs to be highly lipid soluble (base with pKa 8.1).
There are barriers in the mouth that must be overcome.
Drug must be tasteless - good organoleptic properties.
Dosage form must be accepted by the patient.

Question 23

Why are not more drugs delivered through the sublingual route ?

Answer 23

This is because there are a lot of requirements that must be met and there are not many drugs where these requirements are suitable.

Question 24

What does buccal delivery avoid ?

Answer 24

It avoids first pass metabolism.

Question 25

What can affect the kinetics and drug profiles in the plasma ?

Answer 25

The placement of the dosage form in different locations of the mouth.

Question 26

Local drug delivery

Answer 26

Local application of drug to the site of action e.g. mouth ulcers.

Question 27

Systemic drug delivery

Answer 27

The drugs enters the blood circulations and is pumped around the body giving it the chance to reach its target organ e.g. nicotine travels to the brain, the target organ.

Question 28

Buccal treatments of mouth ulcers (apthous stomatitis)

Answer 28

Proprietary preparations - bonjela adult, calgel, iglu gel, anbesol liquid.
These are made up with drugs and excipients.
Drugs - antiseptically, local anaesthetics.
Excipients - taste masking e.g. saccharine sorbitol menthol, colouring e.g. caramel sunset yellow, hydration e.g. water, solubilisers e.g. polyethylene glycol, pH stabilisers e.g. citric acid sodium citrate.

Question 29

Hydrogel formulation

Answer 29

Excipients - polymer network e.g. cellular derivatives PEG, solubilisers e.g. PEG, pH stabilisers e.g. citric acid, thickener/emulsifying agent e.g. glycerol paraffins.

Question 30

How are formulations kept in one place ?

Answer 30

With the use of glue, typically sing a polymer that adheres to a biological surface (bioadhesion) pr t the mucosal surface (mucoadhesion).

Question 31

Requirements of glue

Answer 31

Strong enough to hold the formulation e.g. tablet.
Removable when treatment in complete.
Safe for oral application.
Permits drug diffusion.

Question 32

Mechanism of mucoadhesion

Answer 32

The glue typically becomes tangled in the glycoprotein surface of the cells (that line the mouth) and form proteins with glycoproteins.

Question 33

The ways in which glue can bond to glycoproteins

Answer 33

Physical entanglement - long chains come together and get trapped, mechanical interlocking.
Absorption due to chemical interaction - electrostatic (opposite charges), hydrophobic, hydrogen bonding, VDW interactions.

Question 34

Typically anionic polymers are better at…

Answer 34

… mucoadhesion then cationic or uncharged polymers.