Nasal Route

Describe the anatomical and physiological challenges posed by the nasal routes of administration

• Small and lipophilic drugs can pass olfactory only 

• If use the olfactory bulb too much for nasal route of drugs, the cells with create a defense mechanism (characterisation) and this route will not work anymore 

  • If olfactory is abused, keratinization occurs as a defense mechanism  

  • Medications used: analgesics, vaccines, hormones, opioid analgesics, insulin, glucagon 

  • 

• Respiratory region allows for the systemic 

• 20 min contact time max in respiratory region because of the Mucociliary clearance that clears every 15-20 mins

• Vascularization is higher in respiratory than vestibular

• Enzymatic activity is lower than in the GI tract even though there are 4-5X CYP enzymes due to shorter residence times

Analyze the physiological characteristics needed for nasal drug delivery

• Less than or equal to 300 Da - no other properties matter for absorption

• Bioavailability decreases with increasing MW → 300-1000 Da

• For molecular weight of 1000-6000 Da penetration enhancers will be needed 

• Partition coefficient →  > 1 will have good bioavailability 

  • Coefficient indicated small and lipophilic molecules 

• Solubility, pH, and pKa → drug needs to dissolve in 20 mins if prepared as suspension due to mucociliary clearance 

  • If particles are too big they will be sneezed out 

  • Gels and suspension preferred because they have a higher contact time 

• Other considerations: cyclic molecules are absorbed faster than linear molecules

Formulations

Nasal Drops

• Solutions, Suspensions

Nasal Sprays

• Solutions, Suspensions

Nasal Gels

• Solutions, Suspensions

Nasal Powders

• For drugs with poor stability and/or poor solubility

Characteristics formulations

• pH: 4.5-6.5 (prevent infections)

• Dose: Max 25 mg

• Droplet size: 5-10 micrometers to deposit in respiratory region

• Isotonic: decreases irritation; hypertonic solutions will decrease BA

• Suspension must dissolve within 20 min to have enough absorption before MCC 

• Notes on Excipients and viscosity 

  • Humectants: to prevent nasal irritation and drying out especially for gels 

• Penetration enhancers allow any drugs to go in and can cause infection

Advantages/Disadvantages

I would recomend sprays

excipients

• Viscosity

  • increases n increasing retention time

  • over increase in n decreases diffusion

  • makes gel soothing

• Solubilizers

• Preservatives

• Antioxidants

• humectants: to prevent nasal irritation

• penetration enhancers for large MW drugs

local action target

nasal cavity -congestion, allergies

systemic delivery possible - acute chronic condition

acute chronic condition got pain addiction

can target brain through olfactory region

for both local brain action or systemic action

Nasal drug delivery

as a route of administration utilizes the nasal cavity for drug absorption

Mucociliary Clearance (MCC)

is the physical unidirectional movement and removal of deposited particles and gases dissolved in the mucus from the respiratory tract.

First Pass Effect (1st Pass Effect)

is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation. The first pass effect is often associated with the liver, as this is a major site of drug metabolism

nasal passes this