TD: Buccal delivery Flashcards
What is buccal administration?
What forms are available?
Ø Delivery of drug via the buccal mucosa (the lining of the inside of the cheek) for local or systemic effect.
Ø Placed in the side of the cheek of high up the inside of the upper lip and gum
Ø Tablets, patches, films, gels, ointments or solutions
Ø Small and porous, fast disintegration, rapid release / high molecular weight polymers – adhere by forming a gel – release drug over 1 – 2hrs
Why do we use buccal administration?
Ø Why? – local/systemic effect, rapid drug/release, modified release, increased bioavailability: avoids GI tract/first-pass metabolism
Describe the buccal physiology
Ø Moist membrane lining of the inner surface of the cheeks and the lips forming part of the oral mucosa
Ø Non – keratinised, smooth and freely mobile
Ø Protective role: resistance to injury, microorganisms and noxious substances
Ø Covered with a mucus membrane - mucus is secreted by the major and minor salivary glands as part of saliva
Ø Lipoidal barrier to drugs
Fill in the blanks regarding the oral epithelium:
- Non – keratinised therefore it is up to times more than skin
- Mucus ( charged) – 95% and 5% - vital for swelling and adhesion
- Volume of fluid in oral cavity is ~ 1L in 24 hours and the pH is
- Highly vascularised – rich blood supply (Systemic delivery via )
- Non – keratinised – up to 4000** times more **permeable than skin
- Mucus (negatively charged) – 95% water and 5% glycoproteins - vital for swelling and adhesion
- Volume of fluid in oral cavity is ~ 1L in 24 hours and the pH is 6
- Highly vascularised – rich blood supply (Systemic delivery via jugular vein)
What is the ideal molecule properties for buccal absorpiton?
Small, potent, lipophillic
What are the 2 methods for absorption via the buccal route?
Which is most common
Transcellular and paracellular
What happens in transcellular diffusion?
Which molecules are involved?
- lipophilic molecules (mainly passive diffusion)
- Through lipid rich membranes of epithelial cells
What happens in paracellular diffusion?
What molecules are involved?
What is the relationship with rate and size of molecules?
- hydrophilic molecules/peptides/proteins
- Through aqueous intercellular spaces between cells – smaller area – slower
- Rate proportional to molecular size
- Mucoadhesive interaction with proteins in tight cell junctions can facilitate paracellular transport
What are factors affecting absorption?
Ø Contact time – adhesion, salivary clearance/flow, food/drink ingestion, mastication, speech
Ø Dose, potency, physiochemical characteristics of drug
Ø Mucus layer – protects epithelium = barrier to drugs, diffusion function of molecule size
Ø Enzyme activity – metabolism
Ø Epithelial Barrier – basement membrane
What are methods to improve absorption?
- Increase Adhesion
- Muchoadhesive polymers e.g. cellulose derivatives, starch, chitosan, gums, poly (acrylic acid)–based polymers)
- These wet and swell and stick to mucus membrane
- Increase Drug Solubility
- change molecular form: Prodrugs, salts, co – solvents, cyclodextrins, surfactants
- Enzyme Inhibitors
- Prevent hydrolysis, enhances permeability
- e.g. mucoadhesive polymer to encapsulate drug and prevent degradation
- Permeation enhancer
- alter epithelium – improve stability
What is mucoadhesion?
What is used?
Attachment of a drug carrier system to the mucus layer of a mucosal epithelium to maintain intimate contact for extended periods
Involves chemical or physical bonding
Mucoadhesive polymers: natural, semi-synthetic, synthetic
What must mucoadhesives overcome?
Must overcome:
- Salivary clearance/flow
- Food/drink ingestion
- Mastication
- Speech
Describe the stages of mucoadhesion
1.Contact stage
Intimate contact between mucoadhesive and buccal mucosa
Patient holds dosage form in place until attached – dosage form wets and swells rapidly
- Consolidation Stage
Interpenetration: Mucoadhesive penetrates crevices of epithelium – physical bonding between the glycoprotein (responsible for adhesive and cohesive properties of mucus) and polymer chains
Formation of chemical secondary bonds: Van der Waals, hydrogen, hydrophobic interactions (anionic/non – ionic), electrostatic interactions (if cationic – mucus anionic)
Describe API flow
How can this be improved?
- Unidirectional/multidirectional
- Drug loaded mucoadhesive layer/impermeable backing layer (compressed or coated onto tablet)
- Multidirectional – significant drug loss due to swallowing
- Unidirectional – drug loss minimal
- Must be formulated to ensure the direction of API flow is towards the mucosa
- Use imperable backing - prevent drug loss
What are examples of excipients and their roles
What tests are carried out for buccal preperations?
- In accordance with Bristish Pharmaceopia (BP) for that dosage form i.e. BP tablet testing, viscosity of gel/ointment etc.
- Swelling studies – determination of swelling index over time (in a suitable media) to determine how quickly and long it swells and if erosion occurs.
- Mucoadhesion – as with oral M/R lectures (Dr. Thompson)
- Release studies – in same media as swelling studies
- Differential Scanning Calorimetry – determines interactions between drug and mucoadhesive – may interfere with drug release/swelling/adhesion
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