Oral Drug Delivery Flashcards
3 forms of delivery in oral cavity
sublingual (systemic, mucosal membrane under tongue), buccal (systemic, cheek mucosal membranes) and local drug delivery
Oral Epithelia Outline
Protective mucus layer covering and highly vascularised. Thin sublingual membrane. 2 types of cells:Keratinised (hard plate and gums) and non-keratinised (buccal).
Keratinised eipthelia Outline
Hard plate and gums. Impermiable (not lipophilic), food isn’t allowed through. Function = protection of underlying tissues
Non-keratinised Epithelia Outline
Buccal mucosa. Permeable (lipophilic) allows food through. Intracellular polar matrix.
Benefits/opportunities of drug oral delivery
Easy to admin/remove, high patient acceptability, good blow flow, direct to systemic circulation (skips 1st pass metabolism), paracellular and transcellular metabolism
Oral Cavity Dosage Forms
Liquid (solutions, suspensions, spray and mouthwashes), solid (tablets, losenges, wafers), semisolids (gel, paste, biofilm, gum)
Excipients of sublingual tablets and lozenges
Viscosity enhancers and mucoadhesive polymers
Dosage form considerations
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)
Drug properties effecting dosage form
log P 2 - 4, <500 Daltons, dose 10-20 mg and drug’s 1st pass metabolism
Buccal pH
6.4 - 7.2
Patient Acceptability Outline
Max dose = 25g, size 1-3cm^2., paltable, easy to use (clear instructions and easily portable) and minimse dosing frequency
Considerations for liquid stability
Microbial (Antimicrobials), pH buffer (chemical stability), cosolvents (prevent precipitation), suspending and wetting agents
Considerations for liquid stability
hydroscopicity (packaging necessary for protection)
Permeability enhancers examples and consequences
Bile salts (sodium taurocholate), surfactants (polysorbate 80) and cosolvents (acetone). Can cause irritation in throat
Immediate Release Drugs
Solutions, sprays and sublingual tablets
Slow release drugs
buccal tablet, gums and films
Palatability Excipients
Sweeteners and flavouring
Retention Excipients
viscosity enhancers and mucoadhesive peptides
Permeability Enhancer Excipients
Bile salts, fatty acids, surfactants and complexing agents
Stability Enhancer Excipients
Antimicrobials
Buccal Tablets Outline
Small flat tablets, mucoadhesive, systemic, slow/sustenined release, absorb saliva to sofeten and liberate drug eg prochloprezine (for nausea relief)
Why should tablets not be moved around mouth
Faster liberation of drug (not tested- too quick)
Disadvantages/challenges of oral cavity drug delivery
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
Sublingial tablets outline
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
Difference between sublingual suboxone tablets and film
Drug is absorbed on biofilm and release in mouth by rapid disintegration. Tablet needs to be broken down. Film has faster release
How is film designed
Film casting or direct milling. Buccal films contain impermeable back layer to prevent loss into oral cavity
Dosage forms for local admin
lidocaine viscous oral solution, nystatin suspension and benzocane bioerodable strips
Dosage forms foe systemic admin
nitrolingual sublingual spray, nicorette chewing gums, suboxone sublingual tablets
2 quality control tests for buccal dosage forms
Drug content uniformity (assay of at least 20 dose units)and disintegration testing (conc of drug disintegrated at fixed temp per time)
Drug Release Mechanisms Solution
Drug doesn’t need to be liberated in solution
Drug Release Mechanisms Suspensions
Dissolution
Drug Release Mecahnisms Tablets, wafers, lozenges, microparticles (solids)
Absorb saliva and dissolve. Buccal tablets and lozenges dissolve slow. Sublingual tablets and soft tablets dissolve fast.
Drug release mechanisms of gum, biofilm, films, patches and gels (semisolids)
Dosage form absorbs saliva and drug diffuses out
Why do sublingual dissolve faster then buccal
Sublingual mucosal layer is more permeable and buccual tablets consist of matrix
How do lipophilic drugs diffuse through oral epithelia
Transcellularly (through cell)
How do hydrophilic drugs diffuse through oral epithelia
Paracellularly (between cells)
Drug absorption in oral cavity Outline
low enzyme levels = low metabolism = more whole drug absorbed. First pass metabolism avoided (directly into systemic via jugular vein ).
Label warnings for solution and suspensions
Don’t ingest mouthwash, dose volume, use frequency and whether to take with/after meal (with meal = more sustained = slower stomach emptying).
Label warnings for pastes and gels
dose size, frequency of admin, when to use
Label warnings for patches and biofilms
whether it will dissolve/needs to be removed, dose size, frequency and times.
Label buccal tablets
Don’t chew/swallow tablet. Whether it dissolves/is removed. Rotate site of application
Label sublingual tablets
Don’t chew/swallow don’t drink/eat while tablet is in mouth.
Label sublingual sprays
Priming metered dose before use, hold spray vertically and apply spray under tounge, don’t inhale/swallow spray
Label gum
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
