INTRODUCTION:

The word “cosmetics” is derived from Greek word “kosmtikos”, which means “power, arrangement and ability in beautifying”. The word “Cosmaceuticals” made up of two word one is “cosmetic” and another is “pharmaceutical. Cosmaceuticals are cosmetic products with bioactive ingredients purported to have medical benefits.^1,6Cosmetics are the products which are generally used to beautify the skin and also to purify the skin.^5,12

Cream:

Creams are semi-solid emulsions used to moisturize, protect, and nourish the skin. They consist of a combination of water, oil, and other ingredients like emulsifiers, thickeners, and preservatives. Creams are versatile and come in various formulations to suit different skin types and needs, such as moisturizing creams, antiaging creams, and medicated creams for specific skin conditions. ^1,6,9A cream is a semisolid formulation that typically is applied to the skin and contains more than 20% water and 50% lipid carriers. Another method of incorporating a medicinal molecule is to dissolve or disperse it in an appropriate cream base.⁴

The main aim of our work is to develop a Itraconazole cream which can give various effect, like reduce acne, reduce skin diseases like eczema, psoriasis, wrinkles, rashes etc.^9,10 The topical antifungal agents have varying mechanisms of action and different spectrums of activity and have few adverse reactions or drug interactions.¹⁴

Classification of Cream on the Basis of Function:

• Cleansing and cold cream.

• Foundation and vanishing cream.

• Night and massage cream.

• Head and body cream.

• All-purpose and general cream.⁶

Antifungal Creams:

Antifungal creams are topical medications used to treat fungal infections of the skin, such as athlete’s foot, ringworm, and jockitch. These creams typically contain active ingredients like clotrimazole, miconazole, terbinafine, or ketoconazole, which work by inhibiting the growth of fungi and eliminating the infection. Antifungal creams are applied directly to the affected area and are usually used for a specified duration as directed by a healthcare professional.^1,3

Chronic Mucocutaneous Candidiasis (CMC) is a condition with a wide range of symptoms and has been linked to several immunologic and hormonal disorders. Autosomal or acquisitive factors may predispose the host to CMC infection.²

Antifungal drugs should reach effective therapeutic levels in viable epidermis after dermal administration. The greatest challenge for dermal delivery is stratum corneum, in order to improve its permeability, new formulation approaches have been investigated.⁷

MATERIALS AND METHODS:

Material:

Itraconazole pure drug was obtained as a sample from SSJIPER Jamner, all chemicals were also obtained from my college SSJIPER Jamner.

Pre-formulation Studies:

Preformulation studies include spectroscopic drug identification by UV, and compatibility determination by Fourier-transformed infrared (FTIR/IR) spectroscopy.⁽²⁾ All the physical characterization was observed and compared with the standard monograph in official pharmacopoeia.

UV Spectroscopic Characterization of Itraconazole:

Characterization of itraconazole was performed in methanol by scanning the standard concentration of known drug solution in a range of 200–400 nm to find out the absorption maxima (λmax) of itraconazole.

The Stock Solution’s Preparation:

10 mg of itraconazole was accurately weighed and dissolved in 10 ml of methanol to obtain a concentration of 1000 µg/ml. Subsequently, 5 ml was withdrawn from the above solution, and volume was made up to 100 ml with methanol to get a 50 µg/ml solution.

Preparation of Working Standard:

A series of dilution of a standard solution containing 4–14 µg/ml itraconazole were prepared in methanol using a stock solution. The absorbance was measured at 262 nm against similarly treated blank using a UV spectrophotometer. The procedure was repeated 3 times and the average value of absorbance was calculated.

IR Study of Itraconazole:

The IR band of pure drug was analyzed by using the Potassium bromide (KBr) compression method and observed. The pure drug was mixed with KBr powder [1:100] and then pressed under high pressure in a special transparent disc mould. Afterwards, the disc was placed into IR and record the band. Analyze the band of pure drug for identification. In this work, IR bands of pure drug and drug with excipients used in the formulation were analyzed for the interaction.

Formulation of Itraconazole Cream:

Creams were prepared using the trituration method, as the trituration method is the easiest method for the formulation of cream.

Preparation of aqueous phase:

Glycerin, tween 80, EDTA, and isopropyl myristate were weighed properly and melted in a beaker. The temperature of the water phase is maintained between 65 and 70°C.

Development of cream formulation:

The water portion was then slowly incorporated into the oil phase at 65–70°C and mixed for 10–15 min. with continuous stirring. Then, the dispersion part was added into the above part slowly when the temperature reaches 40°C. The pH of cream was kept between 5.8 and 6.8.

Evaluation Parameters of Cream:

1) Physical Appearance:^2,6,7,10

The prepared topical cream was visually inspected for colour, odour, consistency.

2) pH of Creams:^2,4,5,6,7

For pH determination, 5 gm of the formulated cream was mixed in 50 ml distilled water and measured by using pH meter at 27°C.

3) Viscosity:^2,4,5,6,12

The brookfield digital viscometer was used for the viscosity determination of the formulated creams. According to the standard operating procedure of the viscometer, the adaptor of the viscometer was filled with the formulated cream, and spindle no 2 was rotated at 6rpm, for viscosity determination.

4) Greasiness^2,9

The cream formulation was applied on the skin surface as a thin smear and checked their greasiness.

5) Tube Extrudability^2,7,8,13,14

For extrudability determination, % the quantity of the cream extruded from the tube upon applying finger pressure was evaluated. Better extrudability results from higher extruded quantities from the tube. The prepared cream formulations were filled in 5 gm clean, collapsible aluminium tube having 5 mm opening of the nasal tip. The tube was held between the thumb and index finger, pressure was applied on the tube for 1 second. The amount of extruded cream from the tube upon application of the pressure was evaluated for the determination of tube extrudability.

6) Irritancy^2,4,5,6,10

The allergic reactions, if any, of the formulated creams were investigated by the skin irritancy test. On the left-hand dorsal surface, make a [1 cm2] mark. The cream was then administered to the affected area, and the time was recorded. Then, for an interval of up to 24 hours, it is evaluated for irritancy, erythema, and edema, if any, and a report is made.

7) Spreadability ^2,4,5,6,9

For the spreadability determination wooden block with a pully at one end consisting of apparatus was used. On the ground slide, 2 g of the formulated cream was placed. Another slide which has dimension, provided with the hook was placed on the fixed ground slide.1kg weight was poured on the two slides to create a consistent film of cream. Afterwards, a 30-gm pull was applied to the top slide. The top slide’s time (measured in seconds) to travel 7.5 cm was calculated with the aid of a thread fastened to the hook. Better spreadability is indicated by a shorter interval.

The equation used for calculating Spreadability was:

S = M × L/T

Where, M = Weight (gm) taken,

L = Length of the slide,

T = Time (s) taken.

8) Acid Value ^2,5,10,11,13

Ether and alcohol solvent mixture was used for the acid value determination. 7gm of the formulated cream in 25ml methanol and ether was refluxed until the cream dissolved. 0.1N NaOH was used to titrate the sample solution using phenolphthalein as an indicator. The solution was titrated until pink colour appeared; it was the end point. Noted, in titration, 0.1N NaOH was used. The acid value was calculated:

Acid value = v×5.6/w

Where, v = 0.1N NaOH used in titration

w = weight of formulated cream

9) Drug Content^2,14

In a 250ml volumetric flask, add 0.1 gram of the formulated cream and 20ml 7.4 pH phosphate buffer, and stir for 30min. Using 7.4 pH buffer, the final volume up to 100ml was made, stirred and filtered, and measured the absorbance at 255nm. The drug content was calculated according to beer lambert’s law.

Drug content = (concentration × dilution factor × volume taken) ×conversion factor

RESULTS AND DISCUSSIONS:

1) Pre-formulation Studies-

Evaluation of the physicochemical properties and compatibility testing of the Itraconazole with other formulation ingredients, the pre-formulation studies for pure Itraconazole were carried out.

2) Characterization of Itraconazole by UV-spectroscopy-

The absorption maxima, λ max of Itraconazole by UV scan in phosphate buffer was at 255nm. The calibration curve of Itraconazole by plotting the concentration versus absorbance resulted in a straight line. Hence the result indicates that drug obeys Beer's law show in Fig. no. 1 and 2.

Fig. 1: Absorption maxima (λmax) of Itraconazole

3) Calibration Curve of Itraconazole by using UV-visible Spectroscopy:

To prepare standard chain solutions, we carefully measured (100.0 mg) of standard itraconazole and dissolved with an appropriate amount of distilled water, then transferred to a 100 ml volumetric flask and complete the volume with distilled water. Then it is taken from the standard itraconazole solution with a standard pipette volume (0.5 ml) of the solution and placed in a volumetric flask with a capacity of (100 ml) and extended with distilled water until the full volume and thus we will have prepared the standard solution -1- with a concentration of (5 ppm), then to prepare the standard solution - 2- It was taken from a standard itraconazole solution (0.7 ml) with a standard pipette and the solution is placed in a volumetric flask (100 ml) and we dilute the distilled water until the volume is complete and the solution concentration is (7 ppm), and to prepare the standard solution -3- take (1 ml) as well From a standard itraconazole solution with a standard pipette and placed in a volumetric flask (100 ml ) capacity and extended with distilled water until the volume is complete and the concentration of the solution is (10 ppm), then for Preparation of standard solution No. -4- A volume of (1.5 ml) is taken from the standard itraconazole solution by a standard volumetric pipette. The volume is placed in a volumetric flask (100 ml) and extended with distilled water until the volume is complete. The concentration of the solution is here (15 ppm). To prepare the standard solution -5- The volume (2 ml) of the standard itraconazole solution is taken by a standard volumetric pipette and the volume is placed in a volumetric flask (100 ml) and the solution is extended with distilled water until the volume is complete and the solution concentration here (20 ppm), as shown in table (3). In this method, a series of standard solutions with known concentrations of the substance whose concentration is to be prepared are prepared. After reading the absorption of each solution at a fixed wavelength, we draw the absorption readings in terms of concentration to obtain the calibration curve, and from this curve we can determine the concentration of the unknown solution after knowing its absorption that Give her the device. The concentration is found by the coordinate projection process, where the absorbance of the unknown solution is fixed on the coordinate axis Y, then a straight line is taken parallel to the coordinate axis X until it cuts the straight calibration curve, then a straight line is dropped parallel to the coordinate axis Y on the coordinate axis X and the intersection point with the coordinate axis X The concentration of the unknown substance. Or by the following equation:

C_test = (A_test × C_std) A_std

We determine the absorbances of the standard chain solutions by means of a UV spectrophotometer at a wavelength (255 nm), and then draw the straight line passing through the largest number of points that express the absorbances of the standard chain solutions against their concentrations, so we get the standard curve Figure no. 2.

Table 1: Concentrations of Itraconazole Standard chain Solutions

Standard Solution	Concentration	Absorbance
1	5	0.335
2	7	0.484
3	10	0.691
4	15	1.021
5	20	1.321

Fig. 2: Standard calibration curve of itraconazole

4) FTIR study of Itraconazole:

Compatibility study of drug and mixture of drug with excipients were performed by FTIR technique. The IR spectra of drug excipients study indicating that there is no interaction between Itraconazole and excipients. The major peaks were obtained almost at the same wave numbers which belonging to drug functional groups. On the other hand, in the physical mixtures additional peaks were obtained due to attendance of impurities however there is no influence in the drug peaks. The observation of spectral studies has indicating that there was no significant change in the peaks of drug and excipients mixture. Therefore, no specific interaction between the drug and excipients was observed results were shown in Fig. no: 3 and 4.

Fig. 3: FTIR spectra of Itraconazole

Fig. 4: FTIR spectra of Itraconazole and all excipients

Table 2- Composition of Different Formulation Batches of Itraconazole Cream-

Sr. No.	Ingredients (%)	ITC1	ITC2	ITC3	ITC4	ITC5
1	Itraconazole	1	1	1	1	1
2	Soft Paraffin (Emollient)	4	2	2	4	2.5
3	Cetyl Alcohol	4.5	4	4	5	4
4	Stearic Acid	10	10	10	10	10
5	Glycerin	5	5	5	5	5
6	Tween-80	1	1	1	1	1
7	EDTA	1	1	1	1	1
8	Methyl Paraben	0.2	0.2	0.2	-	0.1
9	Propyl Paraben	-	0.2	0.2	0.4	0.2
10	Triethanolamine	1	0.1	0.1	1	0.1
11	Water	Q.S.	Q.S.	Q.S.	Q.S.	Q.S.

Table 3: Evaluation Parameters of different formulations batches of topical Itraconazole cream

Evaluation Parameters	ITC1	ITC2	ITC3	ITC4	ITC5
Colour	Creamy White	Creamy White	Creamy White	Creamy White	Creamy White
Odour	Characteristics	Characteristics	Characteristics	Characteristics	Characteristics
Feel	Smooth	Not smooth	Smooth	Smooth	Not smooth
Consistency	Good	Not good	Good	Good	Not good
pH	6.4±0.1	6.3±0.1	6.2±0.1	6.6±0.1	6.0±0.1
Viscosity	6462±3.51	8540±5.00	5542±5.03	8857±5.68	7049±4.58
Greasiness	Non-Greasy	Non-Greasy	Non-Greasy	Non-Greasy	Non-Greasy
Tube-Extrudability	Excellent	Good	Good	Good	Excellent
Spreadability (cm.)	16.5±0.49	18.2±0.7	15±1.10	18.9±0.32	14.5±0.76
Acid Value	7.4±0.15	6.1±0.30	6.2±0.20	6.8±0.30	7.8±0.35
Drug Content (%)	90.20	85.81	81.70	94.30	91.22

All the values are expressed as mean ±SD, n=3

Formulation of cream:

Cream of itraconazole was prepared by the trituration method and evaluate various parameters.

DISCUSSION:

Itraconazole topical antifungal creams were prepared using different concentration of preservatives and water absorptive agent with their different batches. Preformulation studies show purity and identification of the drug and all the data were with the specific limits. All the formulation exhibits good tube extrudability. The drug content of all the formulations was within the standard limits. The spreadability of all the formulation was obtained in between 14.5±0.76 and 18.9±0.32 cm (Tables 4 and 5). Formulation ITC4 shows the highest spreadability; 18.9±0.32 cm and formulation ITC4 shows the highest viscosity of 8857±5.68 cp.

CONCLUSION:

The topical antifungal cream of Itraconazole were prepared by the trituration method. Two preservatives and one water absorptive agent used, namely, Methyl paraben, propyl paraben and Cetyl alcohol. Each preservative and water absorptive agent were formulated different formulations with different ratio. Preformulation data were within the specified limits. From the complete discussion, it was concluded that ITC4 is the best formulation among all. The various parameters of ITC4 formulation were found, namely, drug content was 95.55±0.12%, viscosity was 8419± 42.61 cps, spreadability was 8.23±0.13 cm excellent tube extrudability. Hence, topical antifungal cream of itraconazole improves patient compliance, ease of administration, local bioavailability, and better prove for fungal infected patients.

REFERENCES:

1. Gyanesh Kumar Sahu et al. Formulation and Evaluation of Herbal Antifungal Cream, Acta Scientific Pharmaceutical Sciences. 2024; 8(6): 34-40.

2. Janki B. Patel et al. Formulation and Evaluation of Herbal Excipients Based Ketoconazole Cream for Fungal Infection, Journal of Natural Remedies. 2023: 583-592.

3. Arati D Powar and Sachin A. Nitave Polyherbal Antifungal Cream”. World Journal of Pharmaceutical Research. 2022; 11(5): 904-920.

4. Nitin N. Fating et al. Formulation and evaluation of polyherbal vanishing cream. International Journal of Novel Research and Development. 2023; 8(4): 16-21.

5. Vishal Popat Bhagat. Formulation and Evaluation of Moisturizing Cream. International Research Journal of Modernization in Engineering Technology and Science. 2023; 5(5): 6899-6906.

6. Niranjanasree A. C. et al. Formulation and Evaluation of All Purpose Cream Using Box Behnken Design. International Journal of Research Publication and Reviews. 2023; 4: 586-595.

7. Veena S. et al. Formulation and Evaluation of Antifungal Cream of Chlorphenesin. International Journal of Current Pharmaceutical Research. 2021; 13(50: 76-81.

8. Yogesh A. Chaudhari et al. Formulation and Evaluation of Terbinafine and Mometasone of Topical Gel. Journal of Emerging Technologies and Innovative Research. 2022; 9(2): 764-781.

9. Nikhil Nitin Navindgikar. Formulation and Evaluation of Multipurpose Herbal Cream. International Journal of Current Pharmaceutical Research. 2020; 12(3): 25-30.

10. Sharma Pankaj et al. Formulation and Evaluation of Poly Herbal Face Cream. Internationale Pharmaceutica Sciencia. 2013; 3(3): 63-68.

11. Amit Roy et al. Formulation and Development of Herbal Sunscreen Cream. Research Journal Topical and Cosmetic Science. 2014; 5(1): 12-14.

12. Ashish Aswa et al. Preparation and evaluation of polyherbal cosmetic cream. Der Pharmacia Lettre. 2013; 5(1): 83-88.

13. Amol Pimpale. Formulation and Evaluation of Antibacterial, Antifungal Cream of Garlic Oil. International Journal of Trend in Scientific Research and Development. 2018; 3(1): 849-852.

14. A. Premkumar et al. Formulation and Evaluation of Cream Containing Antifungal Agents and Corticosteroid. Journal for Drugs and Medicines. 2015; 6(2): 5-16.

15. Raymond C Rowe, Paul J Sheskey and Siân C Owen. Handbook of Pharmaceutical Excipients. Fifth Edition, 155,737,794.

Received on 04.11.2024 Revised on 10.12.2024

Accepted on 06.01.2025 Published on 28.03.2025

Available online from April 01, 2025

Research J. Topical and Cosmetic Sci. 2025; 16(1):21-26.

DOI: 10.52711/2321-5844.2025.00004

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.