Naphazoline Nitrate Nasal Gel Technology Using Kolkheti Sphagnum

Peat Mineral Water

R. Zazadze1; N. Bakhtadze2; A. Tsertsvadze3; N. Alavidze4; L. Ebralidze5; A. Bakuridze6
1,2,3,4,5,6Department of pharmaceutical technology, Tbilisi State Medical University, Georgia

Abstract-Despite the fact that flu is seasonal it is very massive. Almost everyone who is infected
with flu has rhinitis for which it is used naphazoline nitrate. It is produced in a variety of dosage
forms. Also it is worth to notice that drops are quickly washed from the nasal cavity, and ointments
has more long process and contact with the nasal mucosa. To increase the effectiveness the recent
preferences attach gels. Biopharmaceutical and technological researches show Naphasoline nitrates
0.1% gel recipe and technology. Under normal storages we have studied the stability of gels which
were made on distilled and peat water with Naphasoline nitrate 0.1%. It is estimated that the gel
which is prepared on the peat water is stable for a long time, than the gels prepared on the distilled
water.
I. INTRODUCTION
In modern pharmacy intranasal drug administration is becoming increasingly important. With nose
mucus drugs can be delivered in systemic condition when it requires less time in the appropriate
dose (reach the concentration of active substance in the target organs or tissues). In addition,
intranasal drug receiving is the most appropriate, safe and convenient way, particularly for those
drugs which are not administered well (e.g. peptides, proteins) in the other route except injection.
This way is the best alternative which helps people to avoid injection and also allows them to take
medicines on themselves in a variety of diseases. Nasal mucus good blood supply allows drugs rapid
absorption /2, 3/
Although the intranasal drug delivery system is characterized by a number of advantages there are
also some factors such as mucosal clearance, epithelial and mucosal barriers and enzymatic activity
which affects negatively on drugs delivery system and their distribution. To overcome this problem it
is actually those drugs elaboration such as mucoadhesive gels. Mukoadhesive gels are binded to
mucous membranes and finally the active of drug in the nose is increasing and improving /6/.
Despite the fact that flu is seasonal it is very massive. Almost everyone who is infected with flu has
rhinitis for which it is used naphazoline nitrate. It is produced in a variety of dosage forms. Also it is
worth to notice that drops are quickly washed from the nasal cavity, and ointments has more long
process and contact with the nasal mucosa. To increase the effectiveness the recent preferences
attach gels.
In hydrophilic gel compositions one of the components in most cases is water. Also peat mineral
water is interesting for the researches because of Kolkhetis lowland sphagnum peat (Ispani 2) water
contains essential elements: magnesium, aluminum, silicon, phosphorus, sulfur, potassium, calcium,
manganese, iron, coppers, zinc and silver and it has antibacterial actions /1,4,5,7/.

II. RESEARCH PURPOSES AND OBJECTIVES

The research purpose represents the elaboration of naphazoline nitrates nasal gel recipes and
technology using Kolkheti’s peat ispani-2 mineral water.
For purpose accomplishment we must solve the following tasks:
- Nasal gel base selection based on biopharmaceutical researches using Ispani-2 water;
- Based on the biopharmaceutical research nasal gel recipe development using ispani-2 mineral
water;

DOI : 10.23883/IJRTER.2017.3048.84ZRP 84
 International Journal of Recent Trends in Engineering & Research (IJRTER)
Volume 03, Issue 03; March - 2017 [ISSN: 2455-1457]

- Nasal gel technology development using Ispani 2 water

- Nasal gel standardization and suitability timeframes in the ordinary conditions of storage.

III. THE RESEARCH OBJECTS AND METHODS

The research subject represents Kolkhetis lowland – Ispani 2 mineral water, naphasoline nitrate
substance and gel, auxiliary substances and materials.
For research methods there are used analysis physical-chemical, instrumental and biopharmaceutical
methods:
Determination of pH aqueous gels determination: we add 5 mg of gel to 50-50ml clear water in 50-
60 oC temperature, after carefully shaking we have filtered twice in non-ash filter.
We have studied osmotic feature in simplified model (according to Kruvchinsky). For control we
have used 10% solution of sodium chloride. We were daily using due to constant mass. We have full
osmotic activity gravimetrically and represented in percentage which is relevant to ointment initial
weight.
We have determined as follows: we place in dializator (semiconductor membrane – cellophane with
diameter of 65mm, with pore size of 0,025mm) 1,0g ointment, in dializator camera – the distilled
water. Dializator was in thermostatic condition during the whole period (370C) and we were
weighting with 1-hour interval. We were counting water which was absorbed by the ointment in the
difference in results. Absorbed water we were counting by the formula:
P=
Where:
P – osmotic pressure;
Mn – at the moment of dializator camera mass is with research of samples (g)
M0 – dializator camera mass is before research of samples (g)
MnR – at the moment of dializator camera mass is with control sample (g)
M0R- dializator camera mass is before research of samples (g)
M – Research sample mass. (g)

For colloidal stability determination we have used laboratory centrifuges. The tube was filled up to
2/3, we were weighting with 0,01g accuracy (about 10g), placed it to water bath (42,5±2,5°С) for 20
minutes, dry them and placed to centrifuges. Centrifugation was performed for 5 minutes in
conditions of 6000 r/min. Samples were considered stable if visually dissection was not observed.
We determined research samples thermostability as following: we took 5-6 glass tube with diameter
15mm and a height of 150mm, filled with research object – with 8-10ml and placed in incubator (40–
42)°С for one week, then in refrigerator (10–12) °С for one week too da kept there for 3 days at
room temperature. Stability was measures visually – if dissection was not observed.
Active substances release from research objects we have studies by Francis diffusion cells. Research
was conducted as follows: the agg film was used as a membrane which we placed to 0,1 N
hydrochloric acid for 36 hours (for calcium salts clearing – to stop the separation of air bubbles).
With this rule we have washed egg with distilled water. We have placed research objects on the egg
with 0,2-0,2g weight, distributed evenly, placed between acceptor and donor and clamp it with
special pins. We have applied acceptor label with pH phosphate buffer in the meaning of 6,8 . We
have performed diffuse thermostat within 37±0,10C temperature. We have mixed diffuse area with
magnetic stirrer. We were taking samples every hour and added phosphate buffer which was equal to
the sample. Analyzing samples optical density was determined by Shimadzu UV-1601PC on 280 nm
wave length.
Gels therapeutic properties are depended on basements rational selection because it has a major
effect on the speed and completeness of the medicinal substances release. Naphazoline gel is for
nasal mucosa distances. That is why it is difficult for base containing gel to contact with mucous
membranes and because of that we have selected the hydrophilic nature bases (Table №1).

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 International Journal of Recent Trends in Engineering & Research (IJRTER)
Volume 03, Issue 03; March - 2017 [ISSN: 2455-1457]

Table №1.Napazolinis nitrate gel composition:

Gels composition components Composition compounds, gr

1 2 3 4 5

Naphazoline nitrate 1,0 1,0 1,0 1,0 1,0

Hydroxypropylmethylcellulose 1,5
Carboxymethyl cellulose 2,5
Sodium carboxymethyl cellulose 2,0
Carbopol 1,1
Sodium alginate 2,5
Sodium hydroxide 17% 1,0 ml
Water (ml) (Sphagnum- Ispani 2) up to up to up to up to up to
100 100 100 100 100

Gel preparation procedure with attending compositions: We add to polymers certain quantity also a
certain quantity of water and keep for saturation at room temperature. In the case of carbomer we
make it Alkali by sodium hydroxide 17% solution in values of 6-7. Separately we prepare
naphazoline spirit solutin for which we take a certain quantity and dissolve it in 96 % spirit
in a ratio of 1:10. During the stirring of gel we were adding naphazoline nitrate spirit solution and
mixing it due to obtaining mass.
Naphazoline nitrate intranasal gel determining physical-chemical and technological characteristics
are given in Table №2.

Table №2 Naphazoline nitrate intranasal gel determining physical-chemical and technological

characteristics:
Research preparation Based on the peat water nasal nitrate gel 0,1%
Analysis specification Analysis results
options №1 №2 №3 №4 №5
Description White correspond Correspond Correspond Correspond correspond
homogeneou s s s s s
s gel
Identities Analyzing Correspond Correspond Correspond Correspond correspond
and standard s s s s s
sample
solutions
absorptions
maximums
should be
270nm,
280nm, 287
nm and 291
nm on the
wavelengths
matter.
pH 5,8-7,0 6,4 6,0 6,1 6,7 6,5
Uniformity With naked Correspond Correspond Correspond Correspond correspond
eye visible s s s s s
inclusions
absence
Colloidal The absence Stable Stable Stable Stable stable

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 International Journal of Recent Trends in Engineering & Research (IJRTER)
Volume 03, Issue 03; March - 2017 [ISSN: 2455-1457]

stability of
(visually) delamination
Thermostabilit The absence Stable Stable Stable Stable stable
y of
(visually) delamination
General s.f t.2 P. 71- Correspond Correspond Correspond Correspond Correspond
requirements 73 s s s s s
for the gel
Quantitative Naphazoline 0,1% 0,105% 0.103% 0.101% 0.101%
determination nitrate
content
should be
0,09-0,11%

Table 1 data shows that all research composition satisfie gels quality indicators.
One of gels important features is osmotic effect preserence of absence. In the case of first phase of
wound treatment osmotic effect plays an important role. Osmotic activities results are shown at the
Picture №1.
120
100
Water absorbtion (%)

NaCl(10%)
80
HPMC
60
Na CMC
40
CMC
20
Na Alginate
0
Carbopol
0 5 10 15
Time (hour)

Picture №1. Naphazoline nitrate research compositions osmotic activity determinations results.

Picture #1 shows that natrium chloride 10% solution consumed only 12,7% of water for the first two
hours. After a periodi growth is no longer observed. Based on hydroxypropylmethil-celluloze gel is
characterized by high osmotic activity, for 12 hours water was consumed in 108%. As for the gels,
which are made of carboxymethylcellulose, Sodium alginatis, karbopholys and natrycarboxylmethil-
celluloze they have the same osmotic activity in the identicit period (12 hours) consumed equal to
100% of water.
For optimal composition selection we have studies the dynamics of the release of Naphasoline nitrate
from gels using diffusion cells. Results are reflected on Picture №2.

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 International Journal of Recent Trends in Engineering & Research (IJRTER)
Volume 03, Issue 03; March - 2017 [ISSN: 2455-1457]

120

100

80

Rrelease (%)
Carbopol
60 CMC
Na CMC
40
Na alginate
20
HPMC
0
0 50 100 150
t (minute)

Picture №2. The dynamics of the release of Naphasoline nitrate from gels.

Results (Picture #2) show that Naphasoline nitrate release from carbomer containing gel is virtually
on zero status. Cellulose items bases are in advantage. The best result of active substance release will
be when natrium carboxymethylcellulose will be used. Therefore, further studies will continue in #3
composition.
For naphasoline nithrate gels technological and consumer characteristics predicting we studied
rheological characteristics. For study we have used SNB 2 (Picture №3). We have determined at
rooms temperature (200C) and 340C (the temperature of human skin).

250

200

150

100

50 Displacement tension, Pa.

0
10 20 30 40 50 60 70 80 90

Displacement speed sec–1

Picture №3. Naphasoline nitrate gel rheogram.

The gel Rheogram (Picture #3) shows that the viscosity is sharply dropped with the increase of
deformation, at the same time the tension of displacement is increasing. Such an attitude
demonstrates the structured system.
Based on the experimental researches Naphasoline nitrate gel technology is shown in the following:
Naphasoline nitrate and Sodium carboxylmethylcellulose are immunized on the vibration sieve.
Ethyl spirit and the peat water is measured by the flask.
Sodium carboxylmethylcellulose is prepared in 2,0% solution: distilled water is placed in Sodium
carboxylmethylcellulose and is detained for one day and night. Separately Naphasoline nitrate spirit
solution is made: Naphasoline nitrates 0,1g is dissolved in 96% ethyl spirit.
The next day we add to carboxylmethylcellulose saturated solution Naphasoline nitrate spirit solution
with constant stirring. Homogenization it due to gel and determine preparations quality indicators.
Naphasoline nitrates 0.1% in intranasal gel Naphasoline nitrate content should be 0,09-0,11%.

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 International Journal of Recent Trends in Engineering & Research (IJRTER)
Volume 03, Issue 03; March - 2017 [ISSN: 2455-1457]

On the next stage of the research we have studied Naphasoline nitrate gels stability in normal
storage. We have studied stability of Naphasoline nitrate gels made in purified and peated mineral
water. The research was conducted during one year. We established that with peat Naphasoline
nitrates 0.1% made on peat mineral water gels stability was 250C (60%/RH) during 12 months, but
0.1% Naphasoline nitrates nasal gel prepared on the same conditions is unstable in the seventh
month.

IV. CONCLUSIONS
Biopharmaceutical and technological researches show Naphasoline nitrates 0.1% gel recipe and
technology. With quality characteristics: uniformity, identity, water pH, colloidal and
thermalstability, osmotic activity, viscosity, the active substance release kinetics, quantitative
content, Naphasoline nitrate 0.1% gel which satisfies NTD-s requirements.
Under normal storages we have studied the stability of gels which were made on distilled and peat
water with Naphasoline nitrate 0.1%. It is estimated that the gel which is prepared on the distilled
water is stable for 6 months, but on the peat water – for 12 months.

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