Nasal Drug Delivery Practice Flashcards

A comprehensive set of flashcards covering anatomy, deposition mechanisms, factors affecting absorption, dosage forms, and improvement strategies for nasal drug delivery.

Which structure divides the nasal cavity into two parts?

Nasal septum

What are the membrane folds in the nasal cavity called that increase surface area?

Turbinates

What is the function of the nose hair found in the vestibule?

To filter airborne particles such as dust, pollen and insects.

What are the three primary functions of the nasal mucosa?

Trapping harmful particles in mucus, warming and humidifying inhaled air, and absorption of drugs.

Why are the three primary functions of the nasal mucosa important?

• Trapping harmful particles → so that it can be removed by the cilia and out of the respiratory tract into the GI tract, or to be expectorated out.

• Warming and Humidifying inhaled air → ensure that mucus does not become TOO thick and dried out.

• Absorption of drugs → to ensure that treatment gets to the target site.

Which specific cell type in the nasal mucosa produces mucus?

Goblet cells.

What is the function of ciliated cells in the nasal cavity?

To facilitate mucus movement from the nasal cavity to the nasopharynx and then to the GI tract.

What are the three main deposition mechanisms for nasal drug delivery?

1. Impaction, 2. Sedimentation, 3. Diffusion.

How does impaction, sedimentation and diffusion occur?

Impaction occurs with heavy, larger particles that require faster flow rate in order to move further into the upper respiratory tract. This leads to the particles getting stuck easier and become impacted

Sedimentation occurs with smaller or medium-sized particles that require slower flow rates to move further into the upper respiratory tract. The particles move further in also by gravitational force instead.

Diffusion occurs due to Brownian motion where gas particles slide past and move in random directions from each other.

At what particle size does impaction typically occur in nasal drug delivery?

$$0.5 - 1\,\mu m$$

Which deposition mechanism involves particles settling under gravitational force during slower flow rates?

Sedimentation

What is the mechanism for the deposition of very small particles ($<0.5\,\mu m$)?

Diffusion via brownian motion.

How does mucociliary clearance affect the longevity of drugs in the nasal cavity?

It reduces longevity by clearing mucus toward the nasopharynx to the GI tract for elimination from the body.

Why is nasal drug delivery advantageous in terms of metabolism?

Nasal preparations avoid hepatic first-pass metabolism and the treatment is localized → minimizes systemic side effects

In terms of molecular weight, which molecules diffuse more easily through the nasal mucosa?

Smaller molecules (<300\,Da) diffuse more easily than larger ones (>1000\,Da) due to gravitational force

What type of diffusion do lipophilic drugs typically use to pass through the nasal membrane?

Transcellular diffusion

How does the ionization of a drug molecule affect its partition coefficient ($P$)?

Unionized molecules have a higher partition coefficient ($P$), indicating they are more lipophilic.

What are the three general requirements for nasal dosage forms?

To be effective, to have acceptable safety and stability (chemical and microbiological), and to be acceptable to the patient to ensure compliance.

What are the advantages of using Metered-dose Pump Systems?

More control over dosing, ability to work for dry powder preparations, and good drug distribution.

What is the primary disadvantage of using squeeze bottles for nasal delivery?

They are easily contaminated due to 'suck-back'.

Why are nasal drops often associated with rapid clearance?

Due to the 'swallowing' of the dose.

How can polymers like methylcellulose be used to improve drug availability in the nose?

They increase viscosity, which increases the nasal residence time (contact time).

What is an example of a bioadhesive microsphere used to improve nasal drug residence time?

Starch microsphere

What is the benefit of using a prodrug strategy for nasal delivery?

It provides favorable properties for absorption and changes into the active drug when passing through the nasal cavity → enhances drug targeting effect and cellular uptake.

What are the standard requirements for an effective nasal absorption enhancer?

Effective increase in drug absorption, no permanent damage or tissue change, non-irritant and non-toxic, effective in small amounts, no lag in effect, and must be stable and compatible.

Provide two examples of nasal absorption enhancers mentioned in the notes.

Bile salts and cyclodextrin.

How do we modify the drug structure in nasal delivery systems?

We can..

• alter its chemical structures

• use prodrugs

How does hydrophilic drugs get absorbed into the nasal mucosal membrane?

Through paracellular diffusion mechanisms.

What does Starch microsphere do the nasal mucosa in order to increase nasal residence time?

Starch microsphere adheres to the nasal mucosa in order to remain in the nasal cavity for longer to continue releasing its contents into the bloodstream.

What is the downside of altering the chemical structure of nasal drugs in order to modify the drug’s structure?

• altering the chemical structure can also change the therapeutic and microbiological profile and effect on the target site → can lead to toxicity, side effects or other unintended effects on the target site in the nasal cavity.

How can be enhance nasal absorption — and how do they work to do so?

• Absorption enhancers can be used to alter the structure of nasal mucosal cells to improve drug uptake

Take note that absorption enhancers do not permanently damage or modify nasal tissue, but only temporarily alter the mucosal structure

What are the requirements that are needed for a substance to be consider an absorption enhancer?

• provides effective increase in absorption

• doesn’t cause permanent damage or change to tissues

• non-irritant and non-toxic

• effective in small amounts (reduce toxicity accumulation risk)

• no lag in effect (faster onset of action upon use)

• fulfills other expectations of excipients (stability and compatible with the active ingredients w/o altering its effects)

What are the advantages of using metered-dose pump systems to deliver nasal medication?

• more control over dosing amount

• able to dispense dry powder preparations

• good drug distribution

What makes up the advantages of using metered-dose pump systems?

• more control over dosing due to metered-dose pump system having pre-determined doses that are deposited upon pumping the medication

• good drug distribution due to the nature of using finer powder particles that are lighter and easier to pump and distribute into the nasal cavity.

What are the disadvantages of using metered-dose pump systems?

• local side effects → nasal irritation, epitaxis (nose bleed)

• patient-dependent administration and efficacy → patient might inhaled too forcefully, causing medication to enter the throat instead of remaining in the nasal cavity

What are the advantages of using squeeze bottles to deliver drugs in the nasal cavity?

• better drug absorption → travels to the back of nasal cavity

• covers a large part of the nasal mucosa → drug contact with the nostrils and sinuses, before exiting out the opposite side.

What are the disadvantages of using squeeze bottles?

• increased risk of contamination due to “suck-back” mechanism of the nasal spray bottle.

• patient-dependent administration determines efficacy → patient can tilt the head too far back leading to the drug dripping into the back of the throat.

What are the advantages of using nasal drops as a nasal drug delivery mechanism?

• cheap

• convenient

• simple administration

What are the disadvantages of using nasal drops?

• inaccurate dosing volume due to inconsistency of drop size, or difficulty in determining the administration of nasal drops

• rapid clearance due to swallowing the dose given → drug drips into the back of the throat while tilting their head back

• patient-dependent administration affecting efficacy → patient may either administer too little or too many nasal drops to treat conditions.