Nasal Drug Delivery

Hepatitis B virus surface antigen (HBsAg) loaded N,N,N-trimethyl chitosan nanoparticles (N-TMC NPs) were formulated and studied for controlled intranasal delivery. The size and surface properties of the NPs can be tuned by modifying the concentration of N-TMC and found to be 66 ± 13, 76 ± 9 nm for 0.25 and 0.5 wt.% respectively. Loading of 380 and 760 μl of HBsAg yielded 143 ± 33, 259 ± 47 nm sized spherical N-TMC NPs with highest loading efficiency and capacity of 90–93%, and 96–97% respectively. In vitro drug release analysis ensured 93% cumulative release of HBsAg antigen over prolonged period (43 days). In vivo immunological study was performed using 6–8 weeks old female BALB mice and reveals adjuvants efficiency of NPs for antigen is highly stable and better than standard. Obtained results show that N-TMC NPs can be extensively used in controlled intra nasal delivery to treat various diseases including hepatitis B and allergic rhinitis.

Introduction. Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency
of particular medications proven by therapeutic index may result from differences in composition of particular
formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids
differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim
of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment
of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient.
Material and methods. Three newest and most often used in Poland intranasal glucocorticoids were chosen to
analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution
obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern
Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon
a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography
of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined
with image analysis using commercial substance which colored itself intensively under the influence of water
being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating
deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared.
Results. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 μm. All
tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on
the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this turbinate
as well together with deposition in the middle and superior nasal meatus reaching the region of nasal ceiling
and olfactory field. MF preparation deposited on the anterior part of the inferior turbinate and central part of this
turbinate alike. The area of mucous membrane of lateral wall of nasal cavity on which MF deposited was similar to
the area achieved after the application of FP preparation but much greater than in the case of FF preparation. FF
drug deposition concentrates only on the anterior part of the inferior turbinate. Despite directing the drug to the
lateral wall of the nasal cavity a great proportion of examined preparations deposit also on the nasal septum.
Conclusions The practical application of tridimensional representation (3D printout) of actual geometry of nasal cavity
to establish the deposition of inGCS was proven. Droplet size and the geometry of the aerosol cloud introduced
into the nostril determine the significant deposition of medication droplets in the anterior part of the nasal cavity.
Both physical properties of the drug as well as spraying system applied influence spatial distribution of the drug. The
interaction of the air flow with the layer of deposited fluid plays a major role in the deposition of the drug in the nasal
cavity, therefore it is so important that the drug does not drain by gravity but remains at the site of deposition which
may be reinforced by thixotropic properties of the preparation.

Background
Measurement of nasal mucociliary clearance time with saccharine test is the gold standard for experimental models. Despite all the benefits of such test, it depends on the cooperation from the individual being tested, and rests as well on subjective elements during exploration.
Objective
To determine the feasibility of use of intranasal colorant for the
evaluation of nasal mucociliary clearance, and to describe a novel
technique using topical fluorescein.
Participants and method
An experimental analytic transversal study in which 15 healthy
individuals were tested for both Anderson’s saccharine test and the measurement of mucociliary clearance time with the application of sterile sodium fluorescein and visualizing the transport towards the oropharynx with endoscopes.
Results
The clearance time recorded for both test were similar (p = 0.88).
The results of the saccharine test in our study group were similar to those already published.
Conclusions
As far as the authors are aware, there are not studies published that compare the use of nasal colorant versus the clinical standard for nasal mucociliary clearance time. Using a visual element during
the test adds objectivity and is of particular use for patients with
gustatory disturbances.

Sumatriptan is having high first pass metabolism leading to low bioavailability (absolute Bioavailability 14% in humans).So there is a need to improve the nasal bioavailability by improving nasal penetration because of long duration of retention. The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal drug delivery.The objective of this work was to improve the nasal bioavailability of antimigraine drug, Sumatriptan Succinate by increasing its nasal retention time as well as by means of nasal permeation.To improve the nasal retention time of Sumatriptan Succinate, it has been formulated as In-situ mucoadhesive gel by using blend of Poloxamer 407 and HPMC K4 M. The In-vitro tests performed for mucoadhesive strength and drug diffusion showed that nasal In-situ gelling formulations prepared were having good mucoadhesive strength with very good drug diffusion. The drug release mechanism gel matrices was found to be anomalous and following the Higuchi equation and the diffusion follows Fickian diffusion mechanism. The formulations were evaluated for physiochemical parameter like gelation temperature,viscosity, gel strength, drug content , FTIR and DSC. FTIR and DSC studies were carried out on pure drug as well as for all excipients used in the final formulation and exhibited no interaction.So, this study points to the potential of mucoadhesive In-situ nasal gel of Sumatriptan Succinate in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved nasal bioavailability.