Curcumin And Tea Tree Oil-Loaded Niosomal Gel With Aloe Vera: A Polyherbal Approach To Anti-Acne Therapy

Fig 3: Ether Injection Method

2. MATERIALS AND METHODS

The chemicals that were used are AR/LR grade or the best possible grade available were used as supplied by manufacturer without further purification or investigation.

Chemical’s List

Table 1. List of Chemicals

Equipment’s List

Table 2: List of Equipments

2.1 PRE-FORMULATION STUDIES OF CURCUMIN

Pre-formulation studies are the investigations carried out on an active pharmaceutical ingredient (API) before formulation development to determine its physical, chemical, physicochemical, and mechanical properties. These studies help in selecting suitable excipients, manufacturing methods, dosage forms, packaging materials, and storage conditions to ensure the development of a safe, effective, and stable pharmaceutical product.

The objective of pre-formulation studies is to evaluate the physical and chemical properties of a drug before formulation. These studies help in selecting suitable excipients, developing a stable dosage form, and ensuring the quality, safety, and efficacy of the final product.

A. Curcumin

1.Authentication of curcumin

Curcumin was authenticated using the Certificate of Analysis (COA) provided by Otto Chemie Pvt. Ltd. The supplied curcumin was identified as Curcumine, 99%, with CAS No. 458-37-7 and molecular weight 368.38 g/mol. The certificate reported an assay of 99.05%, with the sample appearing as an orange solid. The reported melting point was 183–188°C, which complied with the specified standard. The product was supplied under Batch No. 0048 and the certificate stated that the product complied with the prescribed quality standards.

2. Organoleptic Evaluation

Curcumin was examined visually for its colour, appearance, and odour. A small quantity of the sample was placed in a clean, dry glass Petri dish and observed under suitable lighting. The odour was assessed carefully by gently wafting the sample towards the nose without direct inhalation.

3. Solubility Study of Curcumin

The solubility of curcumin was determined qualitatively in different solvents. A known amount of curcumin, such as 10 mg, was transferred separately into test tubes containing 1 mL of different solvents, such as distilled water, chloroform, Di-ethyl ether and phosphate buffer pH 7.4. The samples were shaken thoroughly and observed for dissolution. If necessary, the mixtures were allowed to stand and then examined for undissolved particles.

4. Melting Point Determination

The melting point of curcumin was determined using the capillary tube method. A small quantity of finely powdered curcumin was packed into a clean, dry capillary tube. The capillary was attached to a thermometer and placed in a melting point apparatus containing a suitable heating medium. The sample was heated gradually, and the temperature at which the powder began to melt and the temperature at which it completely melted were recorded.

5. Moisture Content (Loss on Drying)

The moisture content of curcumin was determined by the loss-on-drying method. A clean, dry Petri dish was accurately weighed, and the weight was recorded as W₁. Approximately 1 g of curcumin was accurately transferred into the Petri dish, and the combined weight was recorded as W₂. The Petri dish containing the sample was placed in a hot-air oven and dried under the specified conditions until a constant weight was obtained. The dish was then removed from the oven, cooled to room temperature in a desiccator, and weighed accurately. The final weight was recorded as W₃.

The percentage moisture content was calculated using the following equation:

% Moisture content =W2-W3 W2-W1

Where:

W₁ = Weight of empty, dry Petri dish
W₂ = Weight of Petri dish + curcumin before drying
W₃ = Weight of Petri dish + curcumin after drying

6. UV Spectrophotometric Analysis

The maximum absorption wavelength (λmax) of curcumin was determined using a                            UV–Visible spectrophotometer. An accurately weighed quantity of curcumin was dissolved in a suitable solvent based on its solubility, and a stock solution of known concentration was prepared. The stock solution was suitably diluted to obtain an appropriate working concentration for spectrophotometric analysis.

The prepared solution was transferred to a quartz cuvette, and the corresponding solvent was used as the blank. The solution was scanned over a wavelength range of 200–600 nm using a                UV–Visible spectrophotometer. The wavelength at which curcumin exhibited maximum absorbance was recorded as its λmax.

The experimentally obtained λmax was compared with the reported value and was subsequently used for the quantitative estimation of curcumin in the developed niosomal formulation.

7. Ash value

A known quantity of curcumin sample (approximately 2 g) was accurately weighed and transferred into a previously ignited, cooled and weighed silica crucible. The sample was initially heated gently to remove moisture and volatile matter. It was then incinerated in a muffle furnace at about 600°C until a constant weight of ash was obtained. The crucible was allowed to cool in a desiccator and weighed.

The percentage of total ash was calculated using the following formula:

Total Ash(%)=Weight of AshWeight of Sample×100

8. Extractive Value Determination of Curcumin

A known quantity (5 g) of curcumin sample was accurately weighed and macerated with 100 mL of the selected solvent in a closed flask for 24 hours, with frequent shaking during the first 6 hours. The mixture was then filtered. A measured quantity of the filtrate was transferred to a previously weighed evaporating dish and evaporated to dryness. The residue was dried to constant weight and weighed.

The percentage of extractive value was calculated as:

Extractive Value (%)=Weight of sample×Volume of filtrateWeight of dried extract ×Volume of solvent ×100

9. Preliminary Phytochemical Screening of Curcumin

Preliminary phytochemical screening of the curcumin sample was carried out to detect the presence of different classes of phytoconstituents. The following qualitative tests were performed:

a. Test for Phenolic Compounds (Ferric chloride test):

A small quantity of Curcumin was dissolved in a suitable solvent and a few drops of ferric chloride solution were added. The development of a brown colour indicated the presence of phenolic compounds.

b. Test for Flavonoids (Shinoda test):

Curcumin was dissolved in a suitable solvent, followed by the addition of a small amount of magnesium turnings and concentrated hydrochloric acid. The development of pink, red, or orange colour indicated the presence of flavonoids.

c. Test for Tannins (Gelatin test):

A solution of Curcumin was treated with 1% gelatin solution containing sodium chloride. Observation of white precipitate indicated the presence of tannins.

d. Test for Alkaloids (Dragendorff's test):

Curcumin was suitably dissolved and treated with Dragendorff's reagent. Development of orange or reddish-brown precipitate indicated the presence of alkaloids.

e. Test for Saponins (Foam test):

Curcumin was mixed with distilled water and shaken vigorously for several minutes. Observation of persistent froth indicated the presence of saponins.

f. Test for Terpenoids (Salkowski test):

Curcumin was dissolved in chloroform, and concentrated sulfuric acid was carefully added along the side of the test tube. Characteristic reddish-brown colour at the interface indicated the presence of terpenoids.

B. Tea Tree Oil

1. Authentication report of Tea Tree Oil

Tea Tree Oil used in the formulation was procured from Raasa Oils and authenticated based on the supplier-provided Certificate of Analysis (CoA). The CoA identified the material as Melaleuca alternifolia essential oil and reported its physical appearance, colour, odour, solubility, specific gravity, refractive index, optical rotation and flash point, with the tested parameters reported as complying with the specified ranges.

2. Organoleptic Evaluation

Tea Tree Oil was examined visually for its colour, appearance, and odour. A small quantity of the sample was placed in a clean, dry glass Petri dish and observed under suitable lighting. The odour was assessed carefully by gently wafting the sample towards the nose without direct inhalation.

3. Solubility Study

The solubility of Tea Tree Oil was determined qualitatively in selective solvents. Approximately 0.1 mL of tea tree oil was added separately to 1 mL of distilled water, phosphate buffer pH 7.4, and diethyl ether. Each mixture was shaken thoroughly and observed for complete mixing, dispersion, or phase separation.

4. Specific Gravity

The specific gravity of tea tree oil was determined using a calibrated specific gravity bottle (pycnometer). The clean, dry, and empty bottle was accurately weighed, and the weight was recorded as W₁. The bottle was then filled completely with distilled water, ensuring the absence of air bubbles, and fitted with its stopper. The external surface of the bottle was dried carefully, and the bottle was weighed accurately. The weight was recorded as W₂.

The bottle was subsequently emptied, cleaned, and dried thoroughly. It was then filled completely with tea tree oil under the same experimental conditions and fitted with the stopper. The outside of the bottle was wiped dry, and the bottle containing tea tree oil was accurately weighed. The weight was recorded as W₃.

The specific gravity of tea tree oil was calculated using the following equation:

Specific Gravity=W3-W1W2-W1

Where:

W₁ = Weight of the empty specific gravity bottle
W₂ = Weight of the bottle filled with distilled water
W₃ = Weight of the bottle filled with tea tree oil

5. UV-Spectrometric Analysis

Tea Tree Oil was diluted with ethanol to prepare a suitable sample solution. The UV–Visible spectrophotometer was calibrated using ethanol as the blank. The prepared Tea Tree Oil solution was transferred into a quartz cuvette and scanned over the wavelength range of 200–400 nm. The absorbance spectrum was recorded, and the wavelength corresponding to maximum absorbance (λmax) was determined from the obtained spectrum.

6. Partition Coefficient Determination of Tea Tree Oil

The apparent partition coefficient of tea tree oil was determined by the shake-flask method using a gravimetric approach, with ethyl acetate as the organic phase and phosphate buffer pH 7.4 as the aqueous phase. About 1 mL of tea tree oil was accurately measured and transferred into a separating funnel containing 10 mL of ethyl acetate and 10 mL of phosphate buffer pH 7.4. The mixture was shaken gently for 10–15 minutes and allowed to stand until complete separation of the two phases. The upper ethyl acetate layer and lower aqueous layer were separated carefully.

A clean, dry evaporating dish was accurately weighed and recorded as W₁. The separated ethyl acetate phase was transferred into the dish and the solvent was allowed to evaporate completely. After cooling in a desiccator, the dish was weighed and recorded as W₂. The amount of tea tree oil recovered in the organic phase was calculated as W2-W1

The aqueous phase was extracted with fresh ethyl acetate in three successive portions. The combined extracts were transferred to another pre-weighed evaporating dish, and the solvent was evaporated completely. The dish was cooled and weighed as W₄, while the empty dish weight was recorded as W₃. The amount of tea tree oil recovered from the aqueous phase was calculated as W4-W3

Calculate the partition coefficient using:

P=CaCo

Where:

• Ca = concentration of Tea Tree Oil in the Organic phase
• Co = concentration of Tea Tree Oil in the aqueous phase

7. Preliminary phytochemical screening

Preliminary phytochemical screening of the Tea Tree Oil sample was carried out to detect the presence of different classes of phytoconstituents. The following qualitative tests were performed:

a. Test for Terpenoids (Salkowski test):

Tea Tree Oil was mixed with chloroform and concentrated sulfuric acid was carefully added along the side of the test tube. The formation of a reddish-brown colour at the interface indicated the presence of terpenoids.

b. Test for Steroids (Liebermann–Burchard test):

Tea Tree Oil was dissolved in chloroform, followed by the addition of acetic anhydride. Concentrated sulfuric acid was then added carefully along the side of the test tube. The development of a green or bluish-green colour indicated the presence of steroids.

c. Test for Phenolic Compounds (Ferric chloride test):

A small quantity of Tea Tree Oil was diluted with a suitable solvent and a few drops of ferric chloride solution were added. The development of a blue, green, or violet colour indicated the presence of phenolic compounds.

d. Test for Flavonoids (Shinoda test):

Tea Tree Oil was diluted with a suitable solvent, followed by the addition of a small amount of magnesium turnings and concentrated hydrochloric acid. The development of a pink, red, or orange colour indicated the presence of flavonoids.

e. Test for Tannins (Ferric chloride test):

A diluted Tea Tree Oil sample was treated with a few drops of ferric chloride solution. The development of a blue-black or green colour indicated the presence of tannins.

f. Test for Saponins (Foam test):

Tea Tree Oil was mixed with distilled water and shaken vigorously for several minutes. The formation of persistent froth indicated the presence of saponins.

h. Test for Alkaloids (Dragendorff's test):

Tea Tree Oil was suitably diluted and treated with Dragendorff's reagent. The formation of an orange or reddish-brown precipitate indicated the presence of alkaloids.

2.2 Preparation of Curcumin, Tea Tree Oil - Loaded Niosome [CTT-N]

Formulation Code for Curcumin, Tea Tree Oil loaded Niosome

Table 3: Formulation Chart for Curcumin, Tea Tree Oil loaded Niosome

1. Preparation of phosphate Buffer pH: 7.4

Sodium dihydrogen phosphate - 0.31 g
↓
Dissolve in a suitable quantity of distilled water
↓
Add Disodium hydrogen phosphate - 1.09 g
↓
Mix thoroughly until completely dissolved
↓
Make up the volume to 100 mL with distilled water
↓
Calibrate the pH meter
↓
Measure the pH of the prepared buffer
↓
Adjust to pH 7.4 if required

(NaOH to increase pH, HCl to decrease pH)
↓

Phosphate Buffer pH 7.4

2. Preparation of Turmeric – Tea Tree Oil loaded Niosome

Materials:

1. Curcumin
2. Tea Tree Oil
3. Span 20
4. Stearic Acid
5. Phosphate Buffer Ph:7.4
6. Diethyl Ether

Procedure:

Preparation of CTT-N for F3 by Ether injection Method

1. Preparation of organic phase

Fig 4: Preparation of Organic Phase

Span 20 (0.2 g) + Stearic acid (0.1 g)
↓
Accurately weigh and transfer into a clean container
↓
Add Diethyl ether (10 mL)
↓
Mix continuously until a uniform solution is obtained
↓
Add Curcumin (0.025 g)
↓
Add Tea tree oil (0.5 mL)
↓
Mix thoroughly for uniform distribution
↓
Organic phase obtained
↓
Ready for Ether Injection Method

2. Preparation of Aqueous Phase

Fig 5: Preparation of aqueous Phase

Phosphate buffer pH 7.4 (10 mL)
↓
Transfer into a suitable vessel
↓
Heat the buffer to 55–65°C
↓
Maintain at 55–65°C with continuous stirring
↓
Slowly add the prepared organic phase
↓
Diethyl ether evaporates rapidly due to elevated temperature
↓
Continuous stirring promotes vesicle formation
↓
Curcumin–Tea Tree Oil-loaded niosomal dispersion obtained

3. Ether Injection

Fig 6: Ether Injection Method

Prepared organic phase
(Span 20 + Stearic acid + Curcumin + Tea tree oil + Diethyl ether)
↓
Transfer the organic phase into a suitable syringe
↓
Heat phosphate buffer pH 7.4 to 55–65°C
↓
Slowly inject the organic phase through a syringe and needle
↓
Maintain continuous stirring during injection
↓
Ensure gradual and uniform dispersion of the organic phase
↓
Rapid evaporation of diethyl ether due to elevated temperature
↓
Continued stirring promotes vesicle formation
↓
Curcumin–Tea Tree Oil-loaded niosomal vesicles obtained

4. Formation of Curcumin–Tea Tree Oil-Loaded Niosomes

Fig 7: Formation of CTT-N

Diethyl ether evaporates rapidly during injection
↓
Span 20 and stearic acid arrange at the interface
↓
Formation of vesicular structures
↓
Curcumin–Tea Tree Oil-loaded niosomes formed
↓
Continue stirring for 30–45 minutes
↓
Removal of residual diethyl ether and completion of vesicle formation
↓
Cool the niosomal dispersion to room temperature
↓
Collect the prepared niosomal dispersion
↓
Store appropriately for further evaluation

2.3 Evaluation of niosome

1. Appearance

The prepared niosomal formulation was visually examined for its colour, odour, texture, clarity, and physical appearance. The formulation was also checked for the presence of any lumps, aggregates, precipitation, or phase separation. A uniform appearance indicates proper distribution of the formulation components.

2. Homogeneity

The homogeneity of the prepared formulation was evaluated by taking a small quantity of the formulation and examining it visually and by gently spreading it on a glass slide. The formulation was checked for uniform distribution of ingredients, absence of lumps, aggregates, and foreign particles. A homogeneous formulation indicates good uniformity and consistency.

3. pH

The pH of the prepared formulation was determined using a previously calibrated digital pH meter. A suitable quantity of the formulation was placed in a clean beaker, and the electrode was immersed into the sample. The pH was recorded after obtaining a stable reading. The pH was maintained within a range suitable for topical application and skin compatibility.

4. Particle Size

The particle size of the prepared niosomes was determined to evaluate the size and uniformity of the vesicles. The niosomal dispersion was suitably diluted and analyzed using dynamic light scattering (DLS). The average particle size and particle-size distribution were recorded. Smaller and relatively uniform vesicles may provide better distribution and interaction with the skin.

5. Zeta Potential

The zeta potential of the prepared niosomes was determined using a zeta potential analyzer. The sample was suitably diluted and introduced into the instrument for measurement. Zeta potential indicates the surface charge of the vesicles and provides information regarding the physical stability of the niosomal dispersion. A higher absolute zeta-potential value generally indicates better electrostatic repulsion between vesicles and reduced aggregation.

6. Drug Entrapment Efficiency

The entrapment efficiency was determined to evaluate the percentage of curcumin successfully incorporated into the niosomal vesicles. A known quantity of niosomal dispersion was centrifuged to separate the niosomal vesicles from the free or unentrapped drug. The supernatant containing the free drug was separated carefully, and the amount of free curcumin was quantified using a suitable analytical method.

The percentage entrapment efficiency was calculated using:

Entrapment Efficacy=Total Drug-Free (unentrapped drug)Total Drug×100

7. Drug Content

Drug content analysis was performed to determine the amount of curcumin present in the prepared niosomal formulation. A known quantity of formulation was accurately weighed and treated with a suitable solvent to extract the drug. The extract was filtered and analyzed using an appropriate quantitative analytical technique. The obtained drug concentration was compared with the theoretical drug concentration, and the percentage drug content was calculated.

Drug Content (%)=Actual amount of drug presentTheorital amount of drug×100

2.4 Preparation of niosomal gel

Materials:

1. Curcumin–tea tree oil-loaded niosomal dispersion
2. Carbopol 934
3. Aloe vera gel
4. Propylene glycol
5. Glycerin
6. Triethanolamine
7. Methyl paraben
8. Distilled water

Formulation Code for log batch of Niosomal Gel

Table 4: Formulation Chart for Curcumin, Tea Tree Oil loaded Niosomal gel

 1. Hydrate Carbopol for Gel Base

Carbopol 934 – 1 g
↓
Accurately weigh Carbopol 934
↓
Slowly disperse in the required quantity of distilled water
↓
Continuous gentle stirring
↓
Allow to stand for 12–24 hours at room temperature
↓
Complete hydration and swelling of Carbopol particles
↓
Smooth and uniform Carbopol dispersion is obtained
↓
Gel Base

2. Addition of Formulation Ingredients

Hydrated Carbopol 934 gel base
↓
Add Aloe vera gel extract – 5 g
↓
Mix gently until uniformly distributed
↓
Add Propylene glycol – 2 mL
↓
Add Glycerin – 2 mL
↓
Add Methyl paraben – 0.01 g
(dissolved in a small quantity of propylene glycol before addition)
↓
Mix thoroughly to obtain a uniform gel base
↓
Add Triethanolamine (TEA) dropwise
↓
Adjust pH to approximately 5.5–6.0
↓
Smooth and uniform aloe vera gel base obtained

3. Incorporation of Niosomal Dispersion

Prepared curcumin–tea tree oil-loaded niosomal dispersion
↓
Slowly add the niosomal dispersion to the hydrated Carbopol gel base
↓
Add gradually with gentle and continuous stirring
↓
Ensure uniform distribution of niosomes throughout the gel base
↓
Avoid vigorous stirring to minimize vesicle aggregation or damage
↓
Continue gentle stirring until uniformly mixed
↓
Smooth and homogeneous niosomal gel obtained

2.5 Evaluation of niosomal gel

1. Appearance

The prepared niosomal gel was visually examined for colour, odour, texture, clarity, and consistency. The formulation was also checked for the presence of lumps, aggregates, air bubbles, precipitation, or phase separation. A smooth and uniform appearance indicates good physical characteristics of the formulation.

2. Homogeneity

The homogeneity of the prepared gel was evaluated by placing a small quantity of formulation on a clean glass slide and examining it visually. The gel was checked for uniform distribution of ingredients, absence of lumps, aggregates, and foreign particles. The formulation should show a smooth and uniform texture without any visible separation.

3. pH

The pH of the prepared niosomal gel was determined using a calibrated digital pH meter. A suitable quantity of gel was dispersed in distilled water and the electrode was immersed into the sample. The pH was recorded after obtaining a stable reading.

The pH of a topical formulation should preferably be maintained around 5.5–6.5 for better skin compatibility.

4. Viscosity

The viscosity of the prepared niosomal gel was determined using a Brookfield viscometer. An appropriate spindle, such as L4, was selected according to the consistency of the formulation. The viscosity was measured at a predetermined rotational speed and at room temperature. The reading was recorded in centipoise (cP).

5. Spreadability

Spreadability was determined to evaluate the ease with which the niosomal gel spreads over the skin. A known quantity of gel was placed between two clean glass slides. A specified weight was placed on the upper slide, and the time required for the gel to spread over a specified distance was recorded.

The spreadability can be calculated using:

​S=M×LT

Where:

S = Spreadability (g·cm/sec)

M = Weight applied to the upper slide (g)

L = Length travelled by the gel (cm)

T = Time taken (sec)

6. Extrudability

Extrudability was evaluated to determine the ease with which the niosomal gel can be removed from a collapsible tube. A known quantity of gel was filled into the tube and the tube was properly closed. A specified weight was applied to the tube, and the amount of gel extruded through the nozzle was measured.

Extrudability can be expressed as:

E=WL

Where:

E = Extrudability (g/cm)

W = Weight of gel extruded (g)

L = Length of gel extruded (cm)

7. Drug Content

Drug content was determined to evaluate the amount of curcumin present in the prepared niosomal gel. A known quantity of gel was accurately weighed and treated with a suitable solvent to extract the curcumin. The mixture was properly mixed and filtered to remove the gel components. The drug concentration was then determined using a suitable quantitative analytical method such as UV-Visible spectroscopy or HPLC.

The percentage drug content was calculated using:

Drug Content %=Actual amount of drug presentTheroretical amount of drug×100

3. RESULT

3.1 Pre formulation studies

A. Pre formulation studies of Curcumin

1. Authentication of curcumin

The procured Curcumin was authenticated by the supplier/manufacturer and the authentication Certificate of Analysis was obtained. The report confirmed the identity and quality of Curcumin used for the formulation studies. The sample was reported to have 99% purity and was considered suitable for further preformulation and formulation studies.

Fig 8: Authentication Certificate of Analysis of Curcumin

2. Determination of Organoleptic characters

The Organoleptic characters like colour, Odour and state for the given drug sample was studied.

Table 5: Organoleptic test of Curcumin

3. Determination of Solubility

Table 6: Solubility profile of Curcumin

4. Determination of Melting point

Table 7: Melting point of Curcumin

5. Moisture Content (Loss on Drying)

Table 8: Determination of Moisture Content of Curcumin

6. UV Spectrophotometric Analysis

Table 9: λmax of Curcumin

7. Ash Value

Table 10: Determination of Ash Value of Curcumin

   Weight of ash = 30.020 − 30.000 = 0.020g

Ash value=0.0202.000 ×100

8. Extractive Value Determination of Curcumin

Extractive Value %=4.25×100

9. Preliminary phytochemical screening

Fig 9: Preliminary Phytochemical Screening of Curcumin

Table 12: Results of Preliminary Phytochemical Screening of Curcumin

B. Tea Tree Oil

1. Authentication report of Tea Tree Oil

The procured Tea Tree Oil was authenticated using the Certificate of Analysis (COA) provided by the supplier. The certificate confirmed the identity and quality of the Tea Tree Oil. The major constituents were reported to be terpinen-4-ol (35–48%), γ-terpinene (14–28%) and α-terpinene (6–12%), confirming the characteristic composition of Tea Tree Oil. The sample was considered suitable for further formulation studies.

Fig 10: Authentication Certificate of Analysis of Tea Tree Oil

2. Organoleptic Evaluation

Table 13: Organoleptic test of Tea Tree Oil

3. Solubility Study

Table 14: Solubility profile of Tea Tree Oil

4. Specific Gravity

Table 15: Determination of Specific Gravity of Tea Tree Oil

5. UV-Spectrometric Analysis

Table 16: λmax of Tea Tree Oil

7. Partition Coefficient Determination of Tea Tree Oil

Table 17: Determination of Partition Coefficient of Tea Tree Oil

7. Preliminary phytochemical screening

Fig 11: Preliminary Phytochemical Screening of Tea Tree Oil

Table 18: Results of Preliminary Phytochemical Screening of Tea Tree Oil

3.2 Evaluation of niosomes

1. Appearance

Table 19: Appearance of the Prepared Niosomal Formulations (F1–F4)

Fig 12: Prepared Niosomal Formulations (F1–F4)

2. Homogeneity

Table 20: Homogeneity of the Prepared Niosomal Formulations (F1–F4)

3. pH

Table 21: pH of the Prepared Niosomal Formulations (F1–F4)

4. Particle Size

Table 22: Particle Size of Optimized Niosomal Formulation (F3)

Fig 13: Particle Size Analysis of F3 Niosomal Formulation

5. Zeta Potential

Table 23: Zeta Potential of Optimized Niosomal Formulation (F3)

Fig 14: Zeta Potential of F3 Niosomal Formulation

6.  Drug Entrapment Efficacy

Table 24: Entrapment Efficiency of the Prepared Niosomal Formulations (F1–F4)

8. Drug Content

Table 25: Drug Content of the Prepared Niosomal Formulations (F1–F4)

3.3 Evaluation of niosomal gel

1.Appearance

Table 26: Appearance of the Prepared Niosomal Gel Formulations (G1-G3)

2. Homogeneity

Table 27: Homogeneity of the Prepared Niosomal Gel Formulations (G1–G3)

3. pH

Table 28: pH of the Prepared Niosomal Gel Formulations (G1–G3)

Fig 15: pH of Optimized Niosomal Gel Formulation (G3)

4. Viscosity

Table 29: Viscosity of the Prepared Niosomal Gel Formulations (G1–G3)

Fig 16: Viscosity of G3 Niosomal Gel Formulation

5. Spreadability

Table 30: Spreadability of Optimized Niosomal Gel Formulation (G3)

6. Extrudability

Table 31: Extrudability of the Prepared Niosomal Gel Formulations (G1–G3)

7. Drug Content

Table 32: Drug Content of Niosomal Gel Formulations (G1–G3)