Recent trends in nasal drug delivery system - An overview
By - 10/20/2006
(1 vote)
Pravin D.Chaudhari
The purpose of this article is to provide an overview of the factors that
will affect development and designing of nasal formulation. The anatomical
and physiological considerations of the nose, mechanism of nasal drug absorption
and physiochemical factors affecting the formulation design are discussed.
The role of absorption enhancers and strategies to improve nasal drug absorption
also be discussed.
Introduction
Therapy through intranasal administration has been an accepted form of treatment
in the Ayurvedic system of Indian Medicine. In recent years many drugs have
been shown to achieve better systemic bioavailability through nasal route
than by oral administration1.
Advances in biotechnology have made available a large number of protein
and peptide drug for the treatment of a variety of diseases. These drugs are
unsuitable for oral administration because they are significantly degraded in
the gastrointestinal tract or considerably metabolized by first pass effect in
the liver. Even the parenteral route is inconvenient for long term therapy. Of
many alternate routes tried, intranasal drug delivery is found much promising
for administration of these drugs2. In this article, an overview on
the design and development of intranasal drug delivery system is presented.
Anatomy & Physiology of the Nose
The nasal cavity
is divided into two symmetrical halves by the nasal septum, a central partition
of bone and cartilage; each side opens at the face via the nostrils and
connects with the mouth at the nasopharynx. The nasal vestibule, the
respiratory region and the olfactory region are the three main regions of the
nasal cavity. The lateral walls of the nasal cavity includes a folded structure
which enlarges the surface area in the nose to about 150cm2 .This
folded structure includes three turbinates:the superior, the median and the
inferior. In the main nasal airway, the passages are narrow, normally only
1-3mm wide, and this narrows structure enables the nose to carry out its main
functions. During
inspiration, the
air comes into close contact with the nasal mucosa and particles such as dust
and bacteria are trapped in the mucous. Additionally, the inhaled air is warmed
and moistened as it passes over the mucosa; and the high blood supply in the
nasal epithelium.
The submucosal zone of the nasal mucosa directly to
the systemic circulation, thus avoiding firs pass metabolism. Another, perhaps
more familiar, major function of the nose is olfactory region is located on the
roof of the nasal cavity3.
The nasal cavity
is covered with a mucous membrane which can be divided into nonolfactory and
olfactory epithelium areas. The nonolfactory area includes the nasal vestibule,
which is lined with skin-like cells, and respiratory region, which has a
typical airways epithelium.
The Respiratory region4, 5:
The nasal respiratory epithelium is generally described as a pseudo-stratified
ciliated columnar epithelium. This region is considered to be the major site
for drug absorption into the systemic circulation. The four main types of
cells seen in the respiratory epithelium are ciliated columnar cells, non-ciliated
columnar cells, goblet cells and basal cells. Although rare, neurosecretory
cells may be seen but, like basal cells, these cells do not protrude into
the airway lumen. The proportions of the different cell types vary in different
regions of the nasal cavity. In the lower turbinate area, about 15-20% of
the total numbers of cells are ciliated and 60-70% is non-ciliated epithelial
cells. The numbers of ciliated cells increase towards the nasopharynx with
a corresponding decrease in non-ciliated cells. The high number of nonciliated
cells indicates their importance for absorption across the nasal epithelium.
Both columnar cell types have numerous (about 300-400 per cell) microvilli.The
large number of microvilli increases the surface area and this is one of the
main reasons for the relatively high absorptive capacity of the nasal cavity.
The role of the ciliated cells is to transport mucus towards the pharynx.
Basal cells, which vary greatly in both number and shape, never reach the
airway lumen. These cells are poorly differentiated and act as stem cells
to replace other epithelial cells. About 5-15% of the mucosal cells in the
turbinates are goblet cells, which contain numerous secretory granules filled
with mucin. In conjunction with the nasal glands; the goblet cells produce
secretions, which form the mucus layer.
The olfactory region
In human, the olfactory region is located on the roof of the nasal cavities,
just below the cribriform plate of the ethmoid bone, which separates the nasal
cavities from the cranial Cavity. The olfactory tissue is often yellow
in colour, in contrast to the surrounding pink tissue. Humans have relatively
simple noses, since the primary function is breathing, while other mammals
have more complex noses better adapted for the function of olfaction.
Figure 1: A Schematic diagram of olfactory epithelium
Advantages of Nasal Drug Delivery System6, 7:
1) Drug degradation that is observed in the gastrointestinal tract is absent.
2) Hepatic first – pass metabolism is absent.
3) Rapid drug absorption and quick onset of action can be achieved.
4) The bioavailability of larger drug molecules can be improved by means
of absorption enhancer or other approach.
5) The nasal bioavailability for smaller drug molecules is good.
6) Drugs that are orally not absorbed can be delivered to the systemic circulation
by nasal drug delivery.
7) Studies so far carried out indicate that the nasal route is an alternate
to parenteral route, especially, for protein and peptide drugs.
8) Convenient for the patients, especially for those on long term therapy,
when compared with parenteral medication.
Limitation8, 9:
1) The histological toxicity of absorption enhancers used in nasal drug delivery
system is not yet clearly established.
2) Relatively inconvenient to patients when compared to oral delivery systems
since there is a possibility of nasal irritation.
3) Nasal cavity provides smaller absorption surface area when compared to
GIT.
Nasal Drug Absorption:
Mechanism of Drug Absorption:
Several mechanisms have been proposed but the following two mechanism have
been considered predominantly. The first mechanism involves an aqueous route
of transport, which is also known as the paracellular route. This route is
slow and passive. There is an inverse log-log correlation between intranasal
absorption and the molecular weight of water-soluble compounds. Poor bioavailability
was observed for drug with a molecular weight greater than 1000
The second mechanism involves transport through a lipoidal route is also
known as the transcellular process and is responsible for the transport of
lipophilic drugs that show a rate dependency on their lipophilicity. Drug
also cross cell membranes by an active transport route via carrier-mediated
means or transport through the opening of tight junctions. For examples, chitosan,
a natural biopolymer from shellfish, opens tight junctions between epithelial
cells to facilitate drug transport.
Factors affecting nasal drug absorption10, 11:
Many factors affect the systemic bioavailability of nasally administered
drugs. The factors can be attributed to the physiochemical properties of
the drugs, the anatomical and physiological properties of the nasal passage
and the type and characteristics of selected nasal drugs delivery system.
These play significant role for most of the drugs in order to reach therapeutically
effective blood levels after nasal administration. The factors influencing
nasal drug absorption are as follows.
A) Physiochemical properties of drug.
· Molecular size.
· Lipophilic-hydrophilic balance.
· Enzymatic degradation in nasal cavity.
B) Nasal Effect
· Membrane permeability.
· Environmental pH
· Mucociliary clearance
· Cold, rhinitis.
C) Delivery Effect
· Formulation (Concentration, pH, osmolarity)
· Delivery effects
· Drugs distribution and deposition.
· Formulation effect on mucociliary clearance.
· Toxic effect on ciliary function and epithelial membranes.
Absorption Enhancement:
Factors that affect the delivery of drug across nasal mucosa such as surfactants,
dose pH, osmolarity, viscosity, particle size and nasal clearance, drug structure
can be used to advantage to improve absorption.
a) Drug Concentration, Dose and Dose volume
Drug concentration, dose and volume of administration are three interrelated parameters
that impact the performance of the nasal delivery performance. Nasal absorption
of L-Tyrosine was shown to increase with drug concentration in nasal perfusion
experiments. However, in another study, aminopyrine was found to absorb as
a function of concentration. In contrast, bsorption of salicylic acid was
found to decline with concentration. This decline is likely due to nasal mucosa
damage by the permanent.
b) Formulation pH
The pH of a nasal formulation is important for the following reasons:
• To avoid irritation of nasal mucosa;
• To allow the drug to be available in unionized form for absorption;
• To prevent growth of pathogenic bacteria in the nasal passage;
• To maintain functionality of excipients such as preservatives; and
• To sustain normal physiological ciliary movement.
Lysozyme is found in nasal secretions, which is responsible for destroying
certain bacteria at acidic pH. Under alkaline conditions,
lysozyme is inactivated and the tissue is susceptible to
microbial infection. It is therefore advisable to keep the formulation
at a pH of 4.5 to 6.5 keeping in mind the physiochemical properties of the
drug as drugs are absorbed in the unionized form.
c) Buffer capacity
Nasal formulations are generally administered in small volumes ranging from
25 to 200μL with 100 μL being the most common dose volume. Hence,
nasal secretions may alter the pH of the administered dose. This can affect
the concentration of unionized drug available for absorption. Therfore, an
adequate formulation buffer capacity may be required to maintain the pH in
–situ.
d) Gelling/Viscofying agents or Gel-Forming Carriers
According to a various studies, increasing solution viscosity may provide means
of prolonging the therapeutic effect of nasal preparations. A drug carrier
such as hydroxypropyl cellulose was effective for improving the absorption
of low molecular weight but did not produce the same effect for high molecular
weight peptides. Use of a combination of carriers is often recommendation
from a safety (nasal irritancy) point of view.
e) Solubilisers
Aqueous
solubility of drug is always a limitation for nasal drug delivery in solution
conventional solvents such as glycols, small quantities of alcohol, Transcutol
(diethylene glycol monoethyl ether), medium chain glycerides and Labrasol
(saturated polyglycolyzed C8-C10 glycerides) can be used
to enhance the solubility of drugs. Other options include the use of
surfactants or cyclodextrins such as HP-β-cyclodextrin that serve as a
biocompatible solubilizer and stabilizer in combination with lipophilic
absorption enhancers. In such cases, their impact on nasal irritancy should be
considered.
f) Preservatives:
Most nasal
formulations are aqueous based and need preservatives to prevent microbial
growth. Parabens, benzalkonium chloride, phenyl ethyl alcohol, EDTA and benzoyl
alcohol are some of the commonly used preservatives in nasal formulations.
g) Antioxidants:
A small quantity
of antioxidants may be required to prevent drug oxidation. Commonly used
antioxidants are sodium metabisulphite, sodium bisulfite, butylated
hydroxytoluene and tocopherol. Usually, antioxidants do not affect drug
absorption or cause nasal irritation. Chemical/physical interaction of
antioxidants and preservatives with drugs, excipients, manufacturing equipment
and packaging components should be considered as part of the formulation
development program.
Absorption enhancers in nasal drug delivery12, 13:
Unlike the most
small drug molecules, some drugs and peptides do not cross the nasal membrane
efficiently. As a result the nasal bioavailability in simple solution
formulation is very low. The low nasal absorption can be attributed to poor
membrane permeability due to molecular size, lack of lipophilicity or enzymatic
degradation. Enzyme inhibitors can be added to nasal formulation to prevent
enzymatic degradation. The nasal mucosa is almost impermeable to molecular size
greater than 1000
overcome these problems of poor membrane permeability most frequent used
approach is the use of absorption enhancers. They act by one or combination of
the following mechanisms:
1. Alteration of properties of mucosa layer.
2. Opening tight junctions between epithelial cells.
3. Reversed micelle formation between membranes.
4. Increasing the membrane fluidity by,
a) Extraction or leaching of membrane components.
b) Creating disorders in the phospholipids domain in the membrane.
Various types of
penetration enhancers have been evaluated for organic drugs including
surfactants, bile salts, chelators, fatty acid salts, phospholipids, glycyrrhetenic acid derivatives, cyclodextrins and glycols.
Polyoxyethylene-9-lauryl ether (BL-9) in saline solution improves the nasal
absorption of hydralazine in both in-situ and in vivo
nasal absorption studies in rats. Polysorbate 80 (1 %)
in saline solution was observed to promote the nasal absorption of atropine and
hyoscine from nasal solution. The absorption was
rapid, complete and uniform with addition of sodium lauryl
sulphate. A nasal formulation of meclizine
(50 mg/ml) prepared in propylene glycol and 10 % glycerol results in 50 % of
nasal drug absorption, which is equivalent to I.V.therapy.
The nasal absorption of gentamycin (60 mg/ml in saline
solution) in humans has observed to increase by incorporation of 1 % sodium glycocholate and peak serum levels were achieved in 30-60
min.
Most peptides
and proteins show insufficient nasal bioavailability. Number of approaches has
been described to improve their systemic bioavailability. Insulin is poorly
absorbed from nasal mucosa. Many compounds of different chemical structure have
been investigated to promote transnasal insulin absorption. The STDHF enhanced
the effects of absorption enhancers on intranasal insulin delivery in rats,
rabbits and sheep. Among medium chain fatty acids, sodium caprylate
(1%) exhibit the strongest promoting effect. The fatty acids show higher
hemolytic activity than glycocholate. The compound carbenoxolone, glycerrhetenic
acid salt has structures similar to triterpenes and
show promoting effect similar to bile acids and saponins.
Strategies for improving drug availability in nasal administration:
Various
strategies used to improve the availability of the drug in the nasal mucosa,
include
1) To improve the nasal residence time
2) To enhance nasal absorption
3) To modify drug structure to change physicochemical properties
To improve the Nasal residence time:
Mucocilliary
clearance acts to remove the foreign bodies and substances from nasal mucosa as
quickly as possible. One way of delaying clearance is to apply the drug to the
anterior part of the nasal cavity, an effect that is largely determined by the
type of dosage form used. The preparation
could also be formulated with polymers such as methylcellulose, hydroxy propyl
methyl cellulose or polyacrylic acid, in which
incorporation of polymer increases viscosity of the formulation and also acts
as a bio adhesive with mucus. Increase
in residence time does not necessarily lead to increase the absorption; this
concept can be illustrated by considering insulin solution with similar
viscosity containing carbopol and CMC. Here carbopol enhance the absorption
whereas CMC solution doesn’t enhance the absorption of insulin. If we increase
the viscosity, slow diffusion of drug from matrix causes retention in
absorption with CMC. Incase of carbopol causes enhancement of absorption due to
opening the intracellular junctions. One
more lucrative way to increase the nasal resistance time is using biodegradable
microspheres as a carrier for drug delivery. Biodegradable microspheres swell
in presence of water thereby increasing the viscosity. This phenomenon leads to
increase the nasal residential time.
Enhancing nasal absorption:
The
mechanism of action of absorption enhancer is increasing the rate at which drug
passes through the nasal mucosa. Many enhancers act by altering the structure
of epithelial cells in some way, but they should accomplish this while causing
no damage or permanent change to nasal mucosa.
General
requirement of an ideal penetration enhancer are as follows.
1. It should lead to an effective increase in the absorption of the drug
2. It should not cause permanent damage or alteration to the tissue
3. It should be non irritant and nontoxic.
4. It should be effective in small quantity
5. The enhancing effect should occur when absorption is required
6. The effect should be temporary and reversible
7. It should be compatible with other excipients.
Classification of penetration enhancer:
Chemical penetration enhancers are widely used in the nasal drug delivery.
Classification of chemical penetration enhancer includes, following
1) Solvents
2) Alkyl methyl sulphoxides
3) Pyrrolidones
4) 1- Dodecyl azacycloheptan-2-one
5) Surfactants.
Mechanism of penetration enhancers is as follows,
• Increasing cell membrane permeability
• Opening tight junction and formation of intracellular aqueous channels
• Increasing lipophilicity of the charged drug by forming ion pair
• Inhibiting proteolytic activity.
3) Modifying drug structure:
Modification of drug structure without altering pharmacological activity
is one of the lucrative ways to improve the nasal absorption. Here modification
of physiochemical properties such as molecular size, molecular weight, Pka
and solubility, are favorable for nasal drug absorption.
Safety and Efficacy of Absorption Enhancers14
While it is
important to establish the efficacy of absorption enhancers, it is equally imperative
to prove their safety by measuring their effect on the mucociliary transport
rate, nasal morphology and ciliary beat frequency.
(a) Mucociliary transport rate:
It is measured
using a frog palate model to test potential toxicity of absorption enhancers
L-α-lysophosphatidylcholine, sodium deoxycholate and taurocholate, laureth-s
and sodium taurodihydrofusidate irreversibly halted the mucus transport rate.
(b) Nasal Morphology:
This was studied by differing the contact times with the nasal epithelium
using scanning electron microscope to detect gross structural and cellular
changes, ciliary identity as well as prevalence or extra-cellular debris.
Morphological damage caused by enhancers in the increasing order is: GC<<STDHF<<LAURETH-9<DC=TDC.
(c) Ciliary Beat Frequency:
The chicken
embryo tracheal tissue and human adenoid tissue were used to measure the in
vitro reduction of the ciliary beat frequency caused by various enhancers
ranging from laureth-9=DC =GC=TDC (fast and irreversible ciliostasis, brought
about by preservatives like BAK and Mercury compounds).
Formulation Development Research In Nasal Drug Delivery:
Most of the over
the counter nasal preparation are formulated as solution, to treat the nasal
symptoms of allergic rhinitis and common cold. A simple drug solution is
adequate for this purpose as it produces better dispersion over greater surface
area. The nasal residence time of such formulation is short (3-20 min) and
exhibit high inter individual variability. This route provides fast peak levels
in circulation15.
Large
number of drugs has been evaluated for systemic bioavailability after
transnasal administration in experimental animal models. Transnasal
administration of drugs in diverse dosage forms such as sprays, powders, and
microspheres has been attempted for improved residence and bioavailability. The
nasal delivery is receiving attention for management of postoperative pain;
mucosal administration requires only a 1.1-1.5 time higher dose of fentanyl
than i.v. dose. The nasal delivery of vaccines is a very attractive route of
administration in terms of efficacy.
Physiochemical Properties of Drugs:
Chemical form:
The form of a drug can be important in determining absorption. For example,
conversion of the drug into a ester form can alter its absorption. It was
observed that in –situ nasal absorption of carboxylic acid esters of L-Tyrosine
a significantly greater than that of L-Tyrosine.
Polymorphism:
Polymorphism is known to affect the dissolution rate solubility of drug
and thus their absorption through biological membranes. It is therefore advisable
to study the polymorphic stability and purity of drugs for nasal powders and/or
suspensions.
Molecular Weight:
A lenear inverse correlation has been reported between the absorption of
drugs and molecular up to 300
Absorptions decreases significantly if the molecular weight is greater than
1000
of absorption enhancers.
Particle Size:
It has been reported that particle sizes greater than 10 μm are deposited
in the nasal cavity. Particles that are
10
than 1 μm are exhaled.
Solubility and Dissolution Rate:
Drug solubility and dissolution rates are important factors in determining
nasal absorption from powders and suspensions. The particles deposited in
the nasal cavity need to be dissolved prior to absorption. If drugs remain
as particles or is cleared away, no absorption occurs.
Delivery Systems:
The selection of
delivery system depends upon the drug being used, proposed indication, patient
population and last but not least, marketing preferences. Some of these
delivery systems and their importants features are summarized below:
Nasal Drops:
Nasal drops are one of the most simple and convenient systems developed for
nasal delivery. The main disadvantage of this system is the lack of the dose
precision and therefore nasal drops may not be suitable for prescription products.
It has been reported that nasal drops deposit human serum albumin in the nostrils
more efficiently than nasal sprays.
Nasal sprays:
Both solution and suspension formulations can be formulated into nasal sprays.
Due to the availability of metered dose pumps and actuators, a nasal spray
can deliver an exact dose from 25 to 200 μm.The particles size and morphology
(for suspensions)of the drug and viscosity of the formulation determine the
choice of pump and actuator assembly.
Nasal Gels:
Nasal gels are high-viscosity thickened solutions or suspensions. Until the
recent development of precise dosing device, there was not much interest in
this system. The advantages of a nasal gel includes the reduction of post-nasal
drip due to high viscosity, reduction of taste impact due to reduced swallowing,
reduction of of anterior leakage of the formulation, reduction of irritation
by using soothing/emollient excipients and target to mucosa for better absorption.
Nasal Powder:
This dosage form may be developed if solution and suspension dosage forms
cannot be developed e.g., due to lack of drug stability. The advantages to
the nasal powder dosage form are the absence of preservative and superior
stability of the formulation. However, the suitability of the powder formulation
is dependent on the solubility, particles size, aerodynamic properties and
nasal irritancy of the active drug and /or excipients. Local application of
drug is another advantage of this system.
Evaluation of Nasal Formulations:
(A) In vitro nasal permeation studies:
Various approaches used to determine the drug diffusion
through nasal mucosa from the formulation. The two important methodologies to
study the diffusion profile of the drug are discussed here,
In vitro diffusion studies16, 17:
The nasal diffusion cell is fabricated in glass. The water-jacketed recipient chamber has
total capacity of 60 ml and a flanged top of about 3mm; the lid has 3 opening,
each for sampling, thermometer, and a donor tube chamber. The 10 cm long donor
chamber, and a donor tube chamber has total capacity of 60 ml and a flanged top
of about 3mm; the lid has 3 openings, each for sampling, thermometer, and a
donor tube chamber the 10 cm long donor chamber tube has internal diameter of
1.13 cm. The nasal mucosa of sheep was
separated from sub layer bony tissues and stoned in distilled water containing
few drops at genatamycin injection. After the complete removal of blood from
muscosal surface, is attached to donor chamber tube. The donor chamber tube is placed such a way
that it just touches the diffusion medium in recipient chamber. At
predetermined intervals, samples (0.5 ml) from recipient chamber are with draw
and transferred to amber colored ampoules.
The samples withdrawn is suitably
replaced. The samples are estimated for
drug content by suitable analytical technique. Through out the experiment the
temperature is maintained at 37 oC.
(B) In Vivo Nasal Absorption studies1-6:
Animal models for nasal absorption studies
The animal models employed for nasal absorption studies can
be of two types, viz., whole animal or in vivo model and an isolated
organ perfusion or ex vivo model. These models are discussed in detail
below:
Rat Model
The
surgical preparation of rat for in vivo nasal absorption study is
carried out as follows: The rat is anaesthetized by intraperitoneal injection
of sodium pentobarbital. An incision is made in the neck and the trachea is
cannulated with a polyethylene tube. Another tube is inserted through the
oesophagus towards the posterior region of the nasal cavity. The passage of the
nasopalatine tract is sealed so that the drug solution is not drained from the
nasal cavity through the mouth. The drug solution is delivered to the nasal
cavity through the nostril or through the cannulation tubing. The blood samples
are collected from the femoral vein. As all the probable outlets of drainage
are blocked, the drug can be only absorbed and transported into the systemic
circulation by penetration and/or diffusion through nasal mucosa.
Rabbit Model18
The
rabbit offers several advantages as an animal model for nasal absorption
studies:
1. It is relatively cheap, readily available and easily
maintained in laboratory settings
2. It permits pharmacokinetic studies as with large animals
(like monkey)
3. The blood volume is large enough (approx. 300ml)
4. To allow frequent blood sampling (l-2ml)
Thus
it permits full characterization of the absorption
and determination of the pharmacokinetic
profile of a drug. Rabbits (approx. 3 kg) are
either anaesthetized or maintained in the
conscious state depending on the purpose of
study. In the anaesthetized model, the rabbit
is anaesthetized by an intramuscular injection of
a combination of ketamine and xylazine. The rabbit's
head is held in an upright position and the drug
solution is administered by nasal spray into each nostril. During the experiment the body temperature of the
rabbit is maintained at 37°C with the help of a heating pad. The blood samples
are collected by an indwelling catheter in the marginal ear vein or artery.
Dog Model19
The
dog is either anaesthetized or retained hi the conscious condition depending on
the drug characteristics and the purpose of experiment. The dog is
anaesthetized by intravenous injection of sodium thiopental and the anesthesia
is maintained with sodium Phenobarbital. A positive pressure pump through a
cuffed endotracheal tube gives the ventilation. The body temperature is
maintained at 37-38°C by a heating pad. The blood sampling is carried out from
the jugular vein.
Sheep Model20
The
sheep, rabbit and dog models are more practical and suitable for investigating
nasal drug delivery from sophisticated formulations. They permit better evaluation
of the parameters there involved. The in vivo sheep model for nasal
delivery is essentially parallel to that for the dog model. Male in-house bred
sheep are employed since they are free from nasal infections.
Monkey Model
Monkeys
(approx. 8 kg) are anaesthetized, tranquillized or maintained in the conscious
state as per the experimental purpose. The monkey is tranquillized by
intramuscular injection of ketamine hydrochloride or anaesthetized by
intravenous injection of sodium Phenobarbital. The head of the monkey is held
in an upright position and the drug solution is administered into each nostril.
Following the administration, the monkey is placed in a supine position in a
metabolism chair for 5-10 min. throughout the course of study the monkey
breaths normally through the nostrils. The blood samples are collected through
an indwelling catheter in the vein.
Ex Vivo Nasal Perfusion Models21:
Surgical
preparation is the same as that is for in vivo rat model. During the
perfusion studies, a funnel is placed between the nose and reservoir to
minimize the loss of drug solution. The drug solution is placed in a reservoir
maintained at 37°C and
is circulated through the nasal cavity of the rat with a peristaltic pump. The
perfusion solution passes out from the nostrils (through the funnel) and runs
again into the reservoir. The drug solution in the reservoir is continuously
stirred. The amount of drug absorbed is estimated by measuring the residual
drug concentration in the perfusing solution. The drug activity due to
stability problems may be lost during the course of experiment. This is especially
true for peptide and protein drugs that may undergo proteolysis and
aggregation.
Rabbit
can also be used as the animal model for ex vivo nasal perfusion studies.
The rabbit is anaesthetized with parenteral uretliane-acepromazine. A
midline incision is made in the neck and the trachea is cannulated with a
polyethylene neonatal endotracheal tube. The oesophagus is isolated and
ligated. The distal end of the oesophagus is closed with suture and flexible
tygon tubing is inserted into the proximal end and advanced to the posterior
part of the nasal cavity. The nasopalatine tract (that connects nasal cavity to
the mouth) is closed with an adhesive to avoid drainage of drug solution from
the nasal cavity. The drug in isotonic buffer solution is recirculated using a
peristaltic pump.
Conclusion:
The intranasal route is an accessible alternative to
the intravenous route. By using any of the mechanisms proposed, this route
holds future potential for numerous drugs through the development of safe and efficacious
formulations which would be useful for a simple, painless and long-term
therapy. In particular, the nasal drug delivery is a promising alternative to
injectables route of administration. It is very likely that in the near future
more drugs will come in the market intended for systemic absorption in the form
of nasal formulation.
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About Authors:
Pramodkumar Sharma*, Pravin Chaudhari, Pramod
Kolsure, Amit Ajab, Nishant Varia
Pad.Dr.D.Y.Patil Institute of Pharmaceutical Sciences and Research,
Pimpri, Pune- 18, Maharashtra, India.
Dr. Pramodkumar Sharma
Principal
of pharmacy 13, KM Stone,
–
– 201006 (U.P),
Email: pks35_2000@yahoo.com,
Pravin D.Chaudhari*
Assistant Professor, Department of Pharmaceutics, Pad.Dr.D.Y.Patil Institute
of Pharmaceutical Sciences and Research, Pimpri, Pune- 18, Maharashtra, India.
Mobile- 09850179873
E-mail- pdchaudhari_21 @yahoo.co.in, pdchaudhari@rediffmail.com
Mr. Pramod Kolsure
M.Pharm Student, Department of Pharmaceutics, Pad.Dr.D.Y.Patil
Institute of Pharmaceutical Sciences and Research,
Pimpri, Pune- 18, Maharashtra, India.
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Mr. Amit Ajab
M.Pharm Student, Department of Pharmaceutics, Pad.Dr.D.Y.Patil
Institute of Pharmaceutical Sciences and Research, Pimpri, Pune- 18, Maharashtra,
India.
Mr. Nishant Vari
M.Pharm Student, Department of Pharmaceutics, Pad.Dr.D.Y.Patil
Institute of Pharmaceutical Sciences and Research, Pimpri,
Pune- 18,
Maharashtra, India.