Pharmaceutics - Buccal and Sublingual Application Flashcards
why is the oral cavity an attractive site for drug delivery?
because of its ease of administration
what is buccal drug delivery?
through the cheek
what is sublingual delivery?
under the tongue
what is buccal delivery generally used for?
to treat chronic disorders for prolonged-released
what is sublingual delivery used for?
to treat acute disease for fast action
what are the three layers of the mucosal lining of the oral cavity?
- epithelial membrane
- basement membrane
- lamina propia and submucosa
which of the three layers of the mucous lining is richly supplied with blood vessels?
the lamina propia and submucosa
which part of the oral cavity is keratinised?
the oral epithelium in the gingiva and hard palate
which part of the oral cavity if non-keratinised?
the oral epithelium of the soft palate, buccal region, lips and sublingual region
how does absorption take place in the mouth?
by simple passive diffusion through the lipophilic mucosal membrane
two major routes of drug transport by passive diffusion in the oral cavity and the types of drugs that can pass through them?
- transcellular (intracellular) route
- for lipophilic drugs - paracellular (intercellular) route
- for hydrophilic drugs
what factors affect drug solubility?
- lipophilicity
- solubility in saliva
- ionisation
- binding to oral mucosa
- thickness of oral epithelium
if a drug had a LogP >3.3, or LogP<1, what effect will this have on its lipophilicity?
- LogP>3.3 would make it have a poor solubility in the saliva as would be too lipophilic, but would pepnetrate into the lipid layer (transcellular diffusion)
- LogP<1 would make it soluble in the saliva but poorly soluble in lipids so wouldn’t be able to penetrate into the lipid layer.
what are advantages of the buccal and sublingual delivery routes?
- bypass GI tract hostile environment
- bypass liver 1st-pass metabolism
- direct access to systemic circulation
- both rapid absorption and sustained delivery available
- easily administered and can terminate easily
- improved patient compliance as no pain
what are disadvantages of the buccal and sublingual delivery routes?
- smaller absorptive area
- lower permeability than SI
- salivating, swallowing and tongue movement reduces drug availability
- taste of drug
- avoiding swallowing the drug
- may restrict eating and drinking for a period of time
- over hydration of the cavity may lead to slippery surface hence affecting administration
what are the most common buccal formulations?
buccal tablets and patches
To prolong and improve mucosal contact, buccal
formulations should contain what 4 things?
- Mucoadhesive agents
- Penetration enhancers
- Enzyme inhibitors
- Backing membrane
what is the role of mucoadhesive agents?
-they bind to the mucus layer of the membrane to prolong the contact of the formulation with the absorption site
what is the role of penetration enhancers?
-help penetrate the API into the systemic circulation by making the barrier more permeable to the drug. (this must be reversible though so the barrier recovers its properties once the drug is absorbed)
what are the most commonly used mucoadhesive agents?
mucoadhesive polymers e.g. sodium carboxymethylcellulose
what are the most commonly used penetration enhancers?
- fatty acids (disrupt intercellular lipid packaging)
- sufactants (reduce surface tension)
- bile salts (create aqueous channels)
what is the role of enzyme inhibitors?
- improve buccal absorption of drugs (especially proteins)
- it affects enzyme activity by altering the enzyme’s conformation making the drug less accessible to enzymatic degradation
what is the desired molecular size for buccal delivery?
<500 Da (75-100 Da the best)
what is the desired LogP value for optimal drug delivery via the buccal route?
1.6-3.3
what is the ideal half-life for drug delivery by the buccal route?
2-8 hours
what is the role of baking membrane?
- prevents drug loss and offers better patient compliance
- works to attach the drug to the mucus membrane and promotes unidirectional drug release at times
what are commonly used as backing membranes?
- magnesium stearate
- hypromellose
describe the structure of buccal tablets?
small, flat, oval, diameter of 5-8mm
explain the process of tablet disintegration in the buccal region?
- buccal tablet applied to canine fossa
- adhesion to gum
- release of the active substance
- complete disintegration of the tablet
what are monolithic buccal tablets?
- a mixture of drug and bioadhesive with a bidirectional release
- can also have unidirectional release by coating the three sides with hydrophobic substances making them impermeable to water on those sides. So, the fourth side is the only way for drug release.
what is the two-layered matrix for local action buccal tablets?
- an inner bioadhesive layer
- an outer non-bioadhesive layer containing the drug
- allows for bi-directional drug release
what is the two-layered matrix for systemic action buccal tablets?
- drug loaded in inner bioadhesive layer
- outer layer is inert acting as a protective layer.
- can also get drug loaded in non-bioadhesive outer layer and the inner layer being the bioadhesive layer with a water impermeble backing enabling unidirectional release.
describe the structure of buccal patches and films?
- long, flat, thin, high SA
- has an impermeable backing layer and a drug containing layer with mucoadhesive properties
why do patches and films have a higher patient compliance than tablets?
-because they’re flexible and soft
why is drug absorption via the sublingual route rapid?
-sublingual route is relative thin, highly permeable mucosa, profuse blood supply
why must the drug had a rapid disintegration and dissolution rate if delivered sublingually?
-as the sublingual region is constantly washed by saliva and by movements of the tongue
how can we increase the drugs disintegration and dissolution rate?
- small tablet size
- low hardness
- high porosity
what effect does a high porosity and low hardness have on the drug?
it increases it’s friability so more care is needed when packaging and handling the drug.
why are sublingual tablets not coated?
as the saliva will dissolve the coating
