Buccal drug delivery

Question 1

Oral route of adminstration

Answer 1

• Medicaments in solid or liquid form are given by mouth and swallowed
• The dosage form along the GIT and with time, the drug is released and absorbed into the bloodstream
• NB- only absorbed drug (from the bloodstream) can reach its target and elicit an action

Question 2

Advantages of the oral route

Answer 2

• No skill required
• Easy and efficient to pack
• Painless
• Cheap
• Self-administration

Question 3

Challenges of oral route

Answer 3

• Palatability
• First-pass metabolism, breakdown in the stomach
• Unconscious patients, N+V
• The onset of action is slow, emergency use
  *

Question 4

Oral transmucosal drug delivery (Buccal)

Answer 4

• Best of both worlds
• The dosage form is placed within the oral cavity and not swallowed
• Placed under the tongue or buccal cavity
• Drug absorption occurs through the mucous membranes (inner lining) of the mouth, directly into the blood stream
• Tablet, film or spray

Question 5

Physiologic opportunities for buccal drug delivery

Answer 5

• In addition to the advantages of oral delivery
• Easy accessibility/dosage form removal
• Direct access to the systemic circulation via the internal jugular vein
• Avoidance of the first-pass metabolism in drug delivery substrates
• High bioavailability and fast onset of action, low enzymatic activity
• Friendly pH range (6.8) maintained by saliva which contains less mucins compared to git
• Alternative routes for drug that cannot tolerate the harsh conditions of the GIT
• Short epithelial turn-over time (6-8 days) allowing for use of excipients showing mild irritancy
• Relatively immobile mucosa compared to the GIT- allows for much-retentive formulations
• Substantial rate of blood flow yielding a somewhat constant/predictable drug concentration in the bloodstream

Question 6

Structure and functions of the buccal mucosa

Answer 6

• This is stratified squamous cells
• No tight junctions, easier to pass via the paracellular route
• Basement membrane (basal lamina) separates the epithelium from the underlying connective tissue: lamina propia (supporting) and submucosa
• Connective tissues are rich in nerves and blood vessels that empty into the jugular vein
• This can be exploited for systemic delivery of therapeutics

Question 7

Physiologic barriers to buccal delivery

Answer 7

• Insufficient membrane/mucosal permeability poses the largest challenge
• Epithelial thickness and composition vary dependent on-site in the oral cavity
  
  • The sub-lingual area is thinner- the faster onset of action than buccal
• Buccal and sublingual mucosas are non-keratinised, palatal and gingival mucosas are retained
• KKeratinizedcells are impermeable to water opposed to non-keratinised
• Oral transmucosal drug delivery has been targeted to the buccal and sublingual regions

Question 8

Physiologic barriers to buccal delivert

Answer 8

• Membrane coating granules occur in the upper one-third of the epithelium and pose a higher barrier to permeation than keratinisation
• As cells mature, lipophillic contents of the MCGs are extruded into the intracellular spaces causing a further barrier to drug permeation

Question 9

Some formulation strategies to tackle buccal delivery challenges

Answer 9

• Low drug permeation due to thickness of the buccal membrane
  
  • Strategy- use of permeation enhancers e.g. Bile salts, amino acids (trigger amino acid carriers, carrier-mediated absorption)
  • Permeation enhancers now create a gap for other things to travel through include microbes
• Short residence time due to saliva scavenging and accidental swallowing
  
  • Strategy: Add mucoadhesive polymer- stick to mucus till all formulation has dissolved

Question 10

Accessing buccal delivery: in vitro

Answer 10

• Animal tissues
• Cell culture
• Animal tissues
  
  • The sacrifice of an animal just prior to experimentation
  • Removal of buccal mucosa including connective tissues
  • Isolation of buccal epithelium using surgical scissors/ scalpel or dermatome
  • Storage in cold krebs buffer until mounted on diffusion chambers such as franz cells

Question 11

In vitro models for buccal delivery

Answer 11

• Buccal cell cultures
  
  • Removal of cells from an animal and their subsequent growth in a favourable artificial environment
  • Cells may be removed directly from tissues and disaggregated by enzymatic or mechanical means before cultivation (primary culture)
  • Or they may be derived from a cell line that has already been established (continuous cell line)
  • Cells are cultured on solid-semi solid supports (adherent cultures or floating cultures)

Question 12

Marketed buccal formulations

Answer 12

Question 13

Self audit