NASAL and PULMONARY

DRUG DELIVERY SYSTEMS

Presentation by: Dr. Norma Rebello
PULMONARY DRUG DELIVERY SYSTEMS
Weibel model of Lungs (Pulmonary tree)
https://www.newswise.com/articles/computational-evaluation-of-drug-delivery-reveals-room-for-inhalers-impr
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https://www.facebook.com/CopleySci/videos/how-does-a-cascade-impactor-work/10155286936213747/

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 https://www.facebook.com/CopleySci/videos/how-does-a-cascade-impactor-work/10155286936213747/

● The Cascade impactor operates on the principle that in a stream of particles

projected through a series of nozzles and glass slides at high velocity, the
larger particles become impacted first on the lower velocity stages, and the
smaller particles pass on and are collected at higher velocity stages.

● Cascade impaction is the primary method for determination of the

aerodynamic particle size distribution (APSD) of orally inhaled drug
products (OIDPs), due to some unique qualities.
● A cascade impactor fractionates the particles into discrete size bands based
on particle inertia and therefore accounts for how those particles behave in a
moving air stream.
● This makes the technique intuitively relevant to particle deposition in the
lungs. Furthermore cascade impaction allows the determination of
aerodynamic particle size specifically for the drug particles, by virtue of
their collection and subsequent chemical analysis (typically by HPLC).
"How Does a Cascade Impactor Work?" features that Andersen Cascade
◻ Aerosols with particles in the aerodynamic particle size range of 1 to 5 μm
can penetrate deep into the lungs, permitting ready absorption of the drug
into the blood.
◻ For this reason, the US FDA and other regulatory agencies throughout the
world require extensive particle size distribution data from drug sponsors .
◻ The eight-stage Andersen Cascade Impactor (ACI) is the standard
apparatus for the in vitro testing of inhalation drugs (US Pharmacopeia
(USP) Apparatus 1), and has been widely used in the pharmaceutical
industry for assessing the aerodynamic particle size distribution (APSD) in
the aerosols produced by MDIs and dry powder inhalers (DPIs).
◻ In practice, an ACI procedure is very time consuming and labor intensive.
◻ There is a pressing need to replace the ACI with an alternative technique
capable of concurrently performing APSD determination and chemical
identification.
◻ The drug dose delivered beyond the MDI mouthpiece can be categorized
into four fractions: the induction port deposition fraction (IPF), the coarse
particle fraction (CPF), the fine particle fraction (FPF), and the extra-fine
particle fraction (EFPF).
◻ Induction port deposition includes the drug deposited in the USP
throat/glass sampling chamber, and the preseparator (if applicable).
◻ The IPF approximates the delivered drug that is deposited in the throat and
mouth.
◻ The CPF corresponds to particles larger than 5 μm collected within the
cascade impactor and is analogous to particles that penetrate through the
throat but collect in the upper airway due to their relatively large particle
size.
◻ The FPF (particles < 5 μm) is representative of those particles that have a
high probability of penetrating into the deep lung.
◻ The EFPF corresponds to particles smaller than 1 μm that are likely to
reach the peripheral airways and alveoli or be exhaled.
Evaluation of Nasal Drug Delivery Systems
Animal Model:

In Vivo Nasal Absorption Models

• Rat Model:
• This model was first presented in late 1970s.
• the surgical praparation for in vivo nasal absorption is as follows:
• the rat is aesthetized by intraperitoneal injection of sodium
pentobarbital .
• After an incision is made in the neck, the trachea is cannulated
with polyethylene tube.
• Another tube is inserted through the esophagus toward the
posterior part of the nasal cavity.
• The passage of the nasopalatine tract is sealed surgically to to
prevent the the drainage of drug solution from the naal cavity
into the mouth.
• The drug solution is delivered to the nasal cavity through either
the nostril or the esophageal tubing.
• The blood samples are then
collected from the femoral vein.

• Since all the possible outlets in

this rat models are blocked after
surgical preparation, the only
possible way for the drug to be
absorbed and transported into
the systemic circulation is
penetration through the nasal
mucosa.
• The rabbit is a relatively inexpensive and readily available animal and can be
easily maintained in a laboratory setting.
• The blood volume of the rabbit is suffi ciently large (approximately 300 ml) to
permit multiple blood samplings (1-2 ml cach) at a frequency that permits full
characterization of the pharmacokinetic profile of a drug candidate following
nasal delivery.
• The rabbit model described here has been used to study the nasal absorption
and controlled delivery of progesterone and its hydroxy derivatives.
Thank you