Nasal Dosage Forms

Question 1

Advantages of nasal dosage forms

Answer 1

• Convenient administration (cavity capacity - 20 mL, surface area - 180cm2)
• useful area for drug absorption esp to drugs poorly absorbed orally
• absorption generally higher than oral
• rapid and efficient absorption -> highly vascularized
• No hepatic first pass effect

Question 2

Disadvantages of nasal dosage forms

Answer 2

• Degradation of enzymes
• mucociliary clearing/cleaning
• mucosal lining can be a diffusion barrier

Question 3

Absorption mechanism

Answer 3

• Hydrophilic compounds - through aq. channels between cells (pores between cells); molecular size < channel diameter
• Lipophylic compounds - partitioning across cell membranes (molecular size larger than channel diameter); slow rate compared to that of hydrophilic; pH is important

Question 4

Factors affecting nasal drug delivery

Answer 4

1. Physiological (of the skin)
   - speed of mucus flow
   - change in physiological state
   - atmospheric conditions in the nasal cavity
2. Dosage form
   - Physicochemicals of the active drug and excipients
   - Concentration of the active drug
   - Density, viscosity, and pH of the formulation
3. Administration
   - Size of dose
   - Site of deposition

Question 5

How to improve drug availability

Answer 5

• Increase nasal residency time - use viscosity enhancers (e.g. methylcellulose carbopol), use of microspheres (e.g. insulin in microspheres)
• Use absorption enhancers - increase rate at which drugs pass through mucosa - alter structure of epithelial cells (e.g. surfactants, bile acids, cyclodextrins)
  Ideal enhancer properties: produce effective increase in absorption in small quantities; dose does not produce permanent damage to cells; non-irritant, non-toxic, stable and compatible; no lag time for action
• Structural modification e.g. use prodrugs - chemical modification of the drug molecular structure affect its physicochemical properties (salt/ester formation -> increase solubility) -> nasal absorption; chitosan enhance drug transport across mucosal membranes by increasing contact time between the drug and membrane, transiently opening the tight junctions between cells

Question 6

Types of nasal deliveries

Answer 6

• liquid (drops)
• sprays
• gels
• suspensions
• inhalants
• aerosol
• ointment
• sustained release: micro and nano encapsulated spheres/particles

Question 7

Formulations of nasal drops/solutions

Answer 7

• mainly aq. solutions
• antimicrobial preservatives e.g. benzalkonium chloride
• antioxidants e.g. butylated hydroxytoluene
• buffers
• salts to adjust tonicity (0.9% NaCl)
• solubilizing agents/cosolvents e.g. glycols
• viscosity enhancing agents e.g. methylcellulose
• absorption enhancers
  => not limited to these