Oral Drug Delivery

Question 1

3 forms of delivery in oral cavity

Answer 1

sublingual (systemic, mucosal membrane under tongue), buccal (systemic, cheek mucosal membranes) and local drug delivery

Question 2

Oral Epithelia Outline

Answer 2

Protective mucus layer covering and highly vascularised. Thin sublingual membrane. 2 types of cells:Keratinised (hard plate and gums) and non-keratinised (buccal).

Question 3

Keratinised eipthelia Outline

Answer 3

Hard plate and gums. Impermiable (not lipophilic), food isn’t allowed through. Function = protection of underlying tissues

Question 4

Non-keratinised Epithelia Outline

Answer 4

Buccal mucosa. Permeable (lipophilic) allows food through. Intracellular polar matrix.

Question 5

Benefits/opportunities of drug oral delivery

Answer 5

Easy to admin/remove, high patient acceptability, good blow flow, direct to systemic circulation (skips 1st pass metabolism), paracellular and transcellular metabolism

Question 6

Oral Cavity Dosage Forms

Answer 6

Liquid (solutions, suspensions, spray and mouthwashes), solid (tablets, losenges, wafers), semisolids (gel, paste, biofilm, gum)

Question 7

Excipients of sublingual tablets and lozenges

Answer 7

Viscosity enhancers and mucoadhesive polymers

Question 8

Dosage form considerations

Answer 8

systemic (eg reduce inflammation) vs local (eg gum infection), drug factors, patient acceptibility, drug release properties (sustained (long term) vs unsustained and stability (shelf life)

Question 9

Drug properties effecting dosage form

Answer 9

log P 2 - 4, <500 Daltons, dose 10-20 mg and drug’s 1st pass metabolism

Question 10

Buccal pH

Answer 10

6.4 - 7.2

Question 11

Patient Acceptability Outline

Answer 11

Max dose = 25g, size 1-3cm^2., paltable, easy to use (clear instructions and easily portable) and minimse dosing frequency

Question 12

Considerations for liquid stability

Answer 12

Microbial (Antimicrobials), pH buffer (chemical stability), cosolvents (prevent precipitation), suspending and wetting agents

Question 13

Considerations for liquid stability

Answer 13

hydroscopicity (packaging necessary for protection)

Question 14

Permeability enhancers examples and consequences

Answer 14

Bile salts (sodium taurocholate), surfactants (polysorbate 80) and cosolvents (acetone). Can cause irritation in throat

Question 15

Immediate Release Drugs

Answer 15

Solutions, sprays and sublingual tablets

Question 16

Slow release drugs

Answer 16

buccal tablet, gums and films

Question 17

Palatability Excipients

Answer 17

Sweeteners and flavouring

Question 18

Retention Excipients

Answer 18

viscosity enhancers and mucoadhesive peptides

Question 19

Permeability Enhancer Excipients

Answer 19

Bile salts, fatty acids, surfactants and complexing agents

Question 20

Stability Enhancer Excipients

Answer 20

Antimicrobials

Question 21

Buccal Tablets Outline

Answer 21

Small flat tablets, mucoadhesive, systemic, slow/sustenined release, absorb saliva to sofeten and liberate drug eg prochloprezine (for nausea relief)

Question 22

Why should tablets not be moved around mouth

Answer 22

Faster liberation of drug (not tested- too quick)

Question 23

Disadvantages/challenges of oral cavity drug delivery

Answer 23

low innate retention, excess salivation/dry mouth, low dissolution volumes, taste receptor sensitivity, lower permeability then GIT, lower surface area then intestine (lower absorption rate) and tissue irritation

Question 24

Sublingial tablets outline

Answer 24

small, systemic, rapid/unsustained release. Absorb saliva and hydrate to liberate drug (also contains disintegrants and osmotic agents). Prepared by direct compression and wet granulation

Question 25

Difference between sublingual suboxone tablets and film

Answer 25

Drug is absorbed on biofilm and release in mouth by rapid disintegration. Tablet needs to be broken down. Film has faster release

Question 26

How is film designed

Answer 26

Film casting or direct milling. Buccal films contain impermeable back layer to prevent loss into oral cavity

Question 27

Dosage forms for local admin

Answer 27

lidocaine viscous oral solution, nystatin suspension and benzocane bioerodable strips

Question 28

Dosage forms foe systemic admin

Answer 28

nitrolingual sublingual spray, nicorette chewing gums, suboxone sublingual tablets

Question 29

2 quality control tests for buccal dosage forms

Answer 29

Drug content uniformity (assay of at least 20 dose units)and disintegration testing (conc of drug disintegrated at fixed temp per time)

Question 30

Drug Release Mechanisms Solution

Answer 30

Drug doesn't need to be liberated in solution

Question 31

Drug Release Mechanisms Suspensions

Answer 31

Dissolution

Question 32

Drug Release Mecahnisms Tablets, wafers, lozenges, microparticles (solids)

Answer 32

Absorb saliva and dissolve. Buccal tablets and lozenges dissolve slow. Sublingual tablets and soft tablets dissolve fast.

Question 33

Drug release mechanisms of gum, biofilm, films, patches and gels (semisolids)

Answer 33

Dosage form absorbs saliva and drug diffuses out

Question 34

Why do sublingual dissolve faster then buccal

Answer 34

Sublingual mucosal layer is more permeable and buccual tablets consist of matrix

Question 35

How do lipophilic drugs diffuse through oral epithelia

Answer 35

Transcellularly (through cell)

Question 36

How do hydrophilic drugs diffuse through oral epithelia

Answer 36

Paracellularly (between cells)

Question 37

Drug absorption in oral cavity Outline

Answer 37

low enzyme levels = low metabolism = more whole drug absorbed. First pass metabolism avoided (directly into systemic via jugular vein ).

Question 38

Label warnings for solution and suspensions

Answer 38

Don't ingest mouthwash, dose volume, use frequency and whether to take with/after meal (with meal = more sustained = slower stomach emptying).

Question 39

Label warnings for pastes and gels

Answer 39

dose size, frequency of admin, when to use

Question 40

Label warnings for patches and biofilms

Answer 40

whether it will dissolve/needs to be removed, dose size, frequency and times.

Question 41

Label buccal tablets

Answer 41

Don't chew/swallow tablet. Whether it dissolves/is removed. Rotate site of application

Question 42

Label sublingual tablets

Answer 42

Don't chew/swallow don't drink/eat while tablet is in mouth.

Question 43

Label sublingual sprays

Answer 43

Priming metered dose before use, hold spray vertically and apply spray under tounge, don't inhale/swallow spray

Question 44

Label gum

Answer 44

No swallowing, chew until swallowing sensation, begin to chew again after tingling sensation stops (do this for 30 minutes). Do not eat/drink for 15 minutes after gum