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org © 2023 IJCRT | Volume 11, Issue 9 September 2023 | ISSN: 2320-2882

REVOLUTIONIZING SINUSITIS RELIEF:

MICROEMULSION-BASED NASAL SPRAY -
FORMULATION, EVALUATION, AND
OPTIMIZATION
1
Mr. Jay Bhavsar,2Ms. Janki R. Goswami,3Dr. Tejas Patel, 4Dr. Sanjay Chauhan
1
Research Scholar,2Research Scholar,3Associate Professor, 4Professor & Director
1
Pharmaceutics,
1
Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar, 382028, Gujarat, India

Abstract:Sinusitis is a prevalent inflammatory condition affecting the paranasal sinuses, causing

discomfort and reduced quality of life for millions of individuals worldwide. Nasal sprays have emerged as
a promising delivery system for sinusitis treatment due to their localized action and improved drug
bioavailability. In this study, we aimed to develop a microemulsion-based nasal spray formulation using
Basil oil, Eucalyptus oil, and Rosemary oil as the active components for the treatment of sinusitis.The
microemulsion formulation was prepared by combining the selected oils with a suitable surfactant, co-
surfactant, and an aqueous phase. The selection of Basil oil, Eucalyptus oil, and Rosemary oil was based on
their known therapeutic properties in alleviating sinusitis symptoms. Various ratios of the oils were screened
to determine the optimal combination that provided the desired characteristics, such as stability, droplet size,
and drug release properties.The prepared microemulsion-based nasal spray formulation was evaluated for its
physicochemical properties, including pH, viscosity, droplet size, and drug content. In vitro drug release
studies were conducted using a modified Franz diffusion cell to assess the release profile of the active
components from the nasal spray formulation. The optimized formulation was further subjected to stability
testing, including physical appearance, pH, viscosity, and drug content analysis, over a three-month
period.The results indicated that the developed microemulsion-based nasal spray formulation using Basil
oil, Eucalyptus oil, and Rosemary oil as the active components exhibited favorable physicochemical
properties, such as a small droplet size, low viscosity, and uniform drug content. In vitro drug release
studies demonstrated sustained release profiles, which are crucial for prolonged therapeutic effects. Stability
testing revealed that the optimized formulation remained stable, with no significant changes observed in its
physical appearance, pH, viscosity, or drug content during the storage period.In conclusion, the
development of a microemulsion-based nasal spray formulation utilizing Basil oil, Eucalyptus oil, and
Rosemary oil as the active components presents a promising approach for enhancing drug delivery and
efficacy in sinusitis treatment. The optimized formulation displayed desirable physicochemical properties,
sustained drug release, and long-term stability. Future in vivo studies are warranted to evaluate the
therapeutic effectiveness and safety of this microemulsion-based nasal spray for clinical applications in
sinusitis treatment.

Index Terms - Microemulsion, Sinusitis, Essential oils, Nasal Spray.

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I. INTRODUCTION
Sinus, in anatomy, a hollow, cavity, recess, or pocket; a large channel containing blood; a suppurating
tract; or a cavity within a bone. The sinuses are small cavities in the skull that are normally filled with air.
They make mucus, which helps keep the nasal passages clear of allergens and pollutants. Two types of sinus,
the blood-filled and the air-filled sinuses, are discussed below. (1)

1.1 Introduction of Microemulsion

Microemulsions are stable transparent dispersions of water and oil (mixture of various hydrocarbons and
olefins) and surfactant. They are prepared by simple mixing of the components and do not require specific
preparation conditions. There are three kinds of microemulsions: oil dispersed in water (o/w), water dispersed
in oil (w/o), and bicontinuous. The presence of o/w droplets is likely to be a characteristic of microemulsions
where the amount of oil is low. In contrast, the existence of w/o droplets is a characteristic of microemulsions
where the water fraction is low. Droplet diameter varies in the range of 10–140 nm. Bicontinuous
microemulsions may result where the amounts of water and oil are equal. Microemulsion concept was
introduced in the early 1940s by Hoar and Schulman who developed a clear single-phase compound using
titration of a milky emulsion with a medium-chain alcohol. Schulman and coworkers subsequently coined the
term “microemulsion.” Microemulsions have been utilized in several disciplines like fuels, detergents,
agrochemicals, food, cosmetics, and pharmaceutics.

1.2 Introduction of Drug

Composition Of Aromatic Essential Oils:
1.2.1 Introduction of Basil oil
Basil oil used mainly for the treatment of nausea is very popular in Europe, Central Asia, India and Southeast
Asia. Some of its health benefits are: Antioxidant and antimicrobial: Since basil oil is a strong antioxidant
and antimicrobial agent it acts as a natural remedy for sinusitis and congestion. Cures sinus problems: Basil
oil is used for the treatment of sinus infections and also as a cold and influenza reliever. Cineole controls
airway mucus hyper secretion and asthma via anti-inflammatory cytokine inhibition. (2)

1.2.2 Introduction of Eucalyptus oil

Eucalyptus tree native in Australia is used for the extraction of eucalyptus oil (from the leaves of the tree). It
is useful in many ways such as: Treatment of sinus infections: Eucalyptus oil is used as an organic method to
cure sinus infections. It is very efficient in unclogging the nasal passage. Air purifier: Eucalyptus oil helps in
killing germs and bacteria thus acting as an air cleanser. Along with this, its antiseptic and deodorant nature
helps to get rid of airborne irritants that cause sinus inflammation.
Cineole controls airway mucus hyper secretion and asthma via anti-inflammatory cytokine inhibition. (3)

1.2.3 Introduction of Rosemary Oil

Rosemary oil is extracted from the flowering part of the Rosemary plant through steam distillation. Its
usefulness can be seen in:
Boosting of the immune system: Rosemary oil contains antioxidants which help in stimulating our immune
system. A strong immune system helps in fighting sinus infections. Treatment of Respiratory ailments: The
scent of Rosemary oil has been seen to be very efficient in removing throat and nasal congestion thereby
relieving the body from colds, flu, and many sinus problems.
Cineole controls airway mucus hyper secretion and asthma via anti-inflammatory cytokine inhibition. (4)

II. METHODOLOGY
2.1 Materials:
Basil oil, Rosemary oil and Eucalyptus oil was bought from Relief Aroma Oils, Bombay, Iso Propyle
Myristate, Oleic Acid, Castor Oil, Span 80, Tween 80, Iso Propyle Alcohol, PEG400, Methanol, Butan-1-
Ol, Double Distilled Water.

2.2 Methods:
2.2.1 Preparation of Pseudo Ternary Phase Diagram:
Pseudo-ternary phase diagrams were constructed to determine the region into which maximum amount of
ME formation takes place.Surfactant and cosurfactant mixture (Smix) were mixed in different ratios (1:1,
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1:2 and 2:1) to obtain three different ternary phase diagrams. For each phase diagram, oil and Smix were
mixed at ambient temperature in nine different ratios starting from 1:9, 2:8, 3:7 up to 9:1 (% w/w). To these
various mixtures of oil and Smix, distilled water was added dropwise under continuous stirring until
formation of transparent oil in water (O/W) ME takes place. After equilibrium, samples were observed
visually for being clear or turbid. Phase diagrams were plotted using Ternaryplot.com software. (8)

2.2.2 Preparation of Microemulsion:

Drug loaded microemulsions will be prepared by dissolving drug (10%) in oil (isopropyl myristate) and
surfactant (Tween 80)/cosurfactant (butanol) mixture with vigorous stirring at room temperature using
composition of selected formulas until the transparent microemulsions were produced. These drug-loaded
microemulsions will be allowed to equilibrate with gentle magnetic stirring for 15 minutes. Then various
formulated microemulsions were passed through Whatman filter paper (no. 40).(6)

2.2.3 Design of Experiment

In design of experiment have taken Quality Target Product Profile (QTPP) And Critical Quality Attribute
(CQAs), Critical Quality Attribute (CQAs) Analysis, Pre formulation and formulation attributes, In process
(Equipment) Attribute, Post process attribute Of Microemulsion Based Nasal Spray. In design of
experiment, we have taken central composite design with three independent variable (oil, Smix, Water), and
dependent variable and response (Globule size) (9).

2.2.4 Evaluation test

Globule Size: Globule size of microemulsion is measured by using dynamic light scattering (zetasizer,
marlven).
Zeta Potential: Zeta potential of microemulsion is measured by using dynamic light scattering (zetasizer,
marlven).
PDI: PDI of microemulsion is measured by using dynamic light scattering (zetasizer, marlven).
Viscosity: Viscosity of microemulsion is measured by using dynamic light scattering (zetasizer, marlven).
Nasal Skin Irritation Study: Pieces of freshly excised sheep nasal mucosa with a thickness of 0.2 mm were
exposed to CBZ ME for 2 h followed by thorough rinsing with PBS pH 6.4. In two other different sets of
experiments isopropyl alcohol (a strong mucociliary toxin) and PBS pH 6.4 were used instead of CBZ ME
for arriving at a comparative analysis of the extent of damage caused by the preparation. These pieces of
mucosa were fixed in paraffin blocks and fine sections were taken that were stained by eosin
andhematoxylin. The prepared slides were examined with an optical microscope (Olympus, Model BX10,
Japan) and photomicrographs (magnification 400) were taken. (8,10)

III. RESEARCH AND DISCUSSION:

3.1 Pseudo ternary phase diagram
According to the ternary phase diagram the ratio of Smix 1:2 having good microemulsion region. In that the
microemulsion is stable.

Figure 1: Pseudo ternary diagram

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3.2 Design of Experiments

Quality Target Product Profile (QTPP) And Critical Quality Attribute (CQAs) Of Microemulsion Based
Nasal Spray

Table 1: Quality Target Product Profile (QTPP) with their justification

Quality Target Product Profile (QTPP) with their justification.
QTPP Elements Target Justification
Dosage Form Microemulsion based Nasal Essential oil microemulsionhelps in the
Spray dermal drug delivery system.
Dosage Type Rapid release Quick onset of action of essential oils
frommicroemulsion to enhancetherapeutic
effects.
Dosage Strength 10% Incorporated in a single formulation of ME
Route of Nasal Good therapeutic effect
Administration
Drug Permeation Determines the drug permeation Require to determine the amount of
through layers of skin. drugpermeating through the layers of skin.
Drug Retention Required for treating sinusitis Required for achieving higher drug level in
the skinfor enhanced sinusitisaction.
Stability At least 6 months at various To maintain therapeutic potential of the
temperature during.

Table 2: Critical Quality Attribute (CQAs) with their justification

Critical Quality Attribute (CQAs) with their justification.
Quality Attribute of target Is this Justification
the drug product CQA?
Physical Attributes 0 No Physical Attributes of the formulation
werenotconsidered.
Color Light yellow Yes Odor is not directly linked to efficacy andsafety.
Odor Unpleasant No Odor is not directly linked to efficacy andsafety.
Appearance Transparent Yes Microemulsion systems are generally
transparent, thefactor is consideredcritical.
Globule Size Less than 200 nm Yes Smaller globule size of ME will permeation
drugs hencewasregarded as critical.
Percentage of Higher amount Yes Higher amount of surfactant which lowthe
nonionic surfactant but not cause particle size.
toxic effect

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Table 3: Critical Quality Attribute (CQAs) Analysis

Critical Quality Attribute (CQAs) Analysis

Preprocess Attribute In process Attribute Post Process

Preformulation attribute Magnetic stirrer equipment attribute Packaging attribute

Formulation attribute Evaluation equipment attribute Storage and stability attribute

Table 4: Pre-Formulation and Formulation Attributes

Pre formulation and formulation attributes
CQA parameter Iso-propyle Tween 80 Butan 1 ol Formulation
myristate
Physical Parameter Non-critical Non-critical Non-critical critical
Solubility critical critical critical critical
Compatibility Study critical critical critical critical
Viscosity Non-critical Non-critical critical
Melting Point Non-critical Non-critical Non-critical Non-critical

Table 5: In process (Equipment) Attribute

In process (Equipment) Attribute
Equipment
CQA Evaluation equipment
parameter Magnetic stirrer UVinstrumen Centrifuge
t
Time Speed Dilution Time Speed
Particle size Critical Critical Non critical Non critical Non critical
Physical Appearance Critical Critical Non critical Critical Critical
DrugContent Critical Critical Critical Non critical Non critical
Drug Diffusion Critical Critical Non critical Critical Critical

Table 6: Post Process Attribute

Post process attribute
CQA Packaging parameter Storage attribute Stability attribute
Dosage form Critical Critical Critical
Appearance Critical Non critical Critical

Particle size Critical Critical Critical

Turbidity Critical Critical Critical
Drug release Non critical Non critical Critical
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