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Submitted by:
Sama alshihi

Supervisor: Under supervision of
Dr. Ahmed Abdellatif
Assistant Professor at Faculty of Pharmacy,
AL-Qassim University, Kingdom of Saudi Arabia

College of Pharmacy
Qassim University
October 2018


This is to certify that this graduation project proposal entitled “Formulation and evaluation of antifungal activity” is submitted to the College of Pharmacy, Qassim University in partial fulfilment of the requirements for the degree of Doctor of Pharmacy (Pharm.D) by Sama Alshihi under the supervision of Dr. Ahmed Abdellatif.

Signature Signature
Sama Alshihi Ahmed Abdellatif

Table of contents
Page Number
1. Abstract 1
2. Introduction 2
3. Aim 4
4. Research Design and Methods 5
5. References 9


Background: many types of fungi cause disorder in areas that have a warm and moist climate as swimming poll. They can cause a wide variety of diseases such as athlete’s foot, jock itch, and ringworm which either can spread directly or by an infected person. Persons with weak immunity such as who are taking antibiotics, diabetic or cancer patients are infected with fungus easily.

Aim: The aim of this study is to formulate a topical date palm extract cream that is physically and chemically stable, homogenous, nonirritant to skin with a pH suitable to the skin, easy permeability to skin with good antifungal activities as a safe natural and approved FDA product.

Method: formulation of vanishing and cold cream and characterizing of them by ensuring drug content is mixed, cream homogeneity, pH level, physical and chemical stability, easy permeability to skin and evaluating of their antifungal activity by using agar well-diffusion method.

Expected results: Cream will be physically and chemically stable, homogenous, nonirritant to skin with a pH suitable to the skin, easy permeable to skin with good antifungal activities.

Conclusion: Dates are known to have an impactful amount of nutrient, mineral, and vitamins. They can be used as herbal treatment for cold, sore throat and asthma because of tannin content .so we expect that Phoenix dactylifera L. will have good fungicidal properties, penetrate skin easily with a limited side effect. In addition, Dates could treat various types of skin disorder because of phenol, tannin and alkaloid content.



Fungus are type of microorganism that infect human body. Most of them live in wet and hot area .Some fungi can infect healthy humans(Histoplasma and Paracocci- dioides) but they are more common in seriously ill patient such as cancer, immunosuppressed or patient with transplanted organ(Candida and Cryptococcus) (Hall and Noverr, 2017).

Phoenix dactylifera L (date palm) is a monocot plant from Arecaceae family (Khan et al., 2018). Dates are high source of energy. They contain carbohydrate, fat, protein, fiber, minerals and a small amount of vitamins such as C, B1, B2, A, riboflavin, niacin and thiamine (Assirey, 2015, Essa et al., 2015, Farouk et al., 2018). Carbohydrate and fiber content varies depending on ripening stage, date cultivar and environmental condition (Viquez et al., 2018). Dates also contain anthocyanins, phenolics, sterols, carotenoids, procyanidins and flavonoids (Olabisi and Ojotule, 2017). They have been used as traditional medicine for treating a diverse disorder such as fever, inflammation, memory disorder and paralysis (Stephen et al., 2018). Now days studies discovered that date have a countless health benefits for human being which are antioxidant , anticancer, hepatoprotective, nephroprotective, neuroprotective, gastrointestinal protective, anti-diabetic, antimicrobial, antiviral ,antihyperlipidemic , antidiarrheal ,laxative and sexual improvement activity (Assirey, 2015, Hamad et al., 2015,El-Far et al., 2016,Olabisi and Ojotule, 2017).

Previous studies of Phoenix dactylifera L have tested its antibacterial and antifungal activity. Experiments showed that phenol content is toxic and have a good inhibitory effect against different types of bacteria and fungi.Inhibitory degree increase with the increase in extract concentration (Ismail and Altuwairki, 2016, Olabisi and Ojotule, 2017).Nystatin, amphotericin B, anidulafungin, griseofulvin, terbinafine. flucytosine and different azole antifungal medications are a treatment of diverse types of fungal infection but they have potential adverse effects and life threating in some conditions (Reiss et al., 2017).

A previous study has prepared phoenix dactylifera L cosmetic cream was it found to have anti-acne, whitening, anti-aging and anti-inflammatory effect (Meer et al., 2017). The cream is better than other dosage forms because it increases patient compliance, limit body exposure to medication, which can lower the number of side effect, avoid first-pass metabolism and drug level fluctuation. In addition, a patient can apply it easily (Pawar et al., 2013, Grumezescu, 2017).

Vanishing cream is oil in water emulsion that is non-sticky, less oily and messy texture, easily removed by water and most users preferred dosage form and can be used during the day (Dhase et al., 2014). While cold cream is water in oil emulsion that prevents water loss from the outer layer of skin and help dry skin become more moisturized which can be suitable to use at bedtime (Sahu et al., 2016)

In this study, we will formulate a vanishing and a cold cream containing Phoenix dactylifera L. as the active constituent and evaluate their antifungal activity.


Formulation of date palm extract vanishing cream that contains active constituent, nonirritant to the skin, physically and chemically stable, homogenous with pH of 5.5 and ensuring of its permeability to the skin, and evaluating cream antifungal activity by testing them on several types of fungus.



To prepare Vanishing cream
Vanishing cream is emulsion base which is oil in water, the oil phase gives the cream shine and pearl look because of stearic acid in the oil. To form an emulsion, the alkali will react with stearic acid to form stearate soap. Then mix Sodium Hydroxide (NaOH) with Potassium Hydroxide (KOH) to give cream hard and soft properties. The different between Vanishing cream and cold cream is vanishing cream have a larger quantity of water phase. The benefits of vanishing cream are:1- easy to rub on skin 2- not greasy 3- skin cooling.
Objective: To prepare 30 g of Vanishing Cream (o/w)
Sr. No Ingredients Formula
1 Stearic Acid 18 gm
2 Potassium Hydroxide 0.8 gm
3 Glycerine 5 gm
4 Propyl Paraben 0.01 gm
5 Methyl Paraben 0.1 gm
6 Purified Water 76.2 gm

Apparatus: Porcelain dish (china dish), Water bath, Ointment Spatula, Thermometer, Beaker
Chemicals: Stearic acid, Potassium hydroxide, Glycerine, Propyl paraben, Methyl paraben
1. Heat the oil phase (i.e. stearic acid) and water phase (i.e. potassium hydroxide, glycerine, propyl paraben, methyl paraben, water) to approximately 65°C.
2. Add the aqueous phase slowly to the oil phase with stirring to form a crude emulsion.
3. Cool to nearly 50°C and homogenize.
4. Cool with agitation until congealed.
To prepare 30 g of Cold Cream (w/o)
Method for Preparation of Creams
??Heat oil-soluble materials over steam bath until melted in evaporating dish.
??Heat all water-soluble materials to approximately same temperature
??Add water (2) to Oil (1) with constant stirring.
??Remove evaporating dish from heat; continue stirring until at room temperature.
NOTE: Always add water phase to oil phase because oil phase tends to remain in dish.

Apparatus: Porcelain dish (china dish), Water bath, Ointment Spatula, Thermometer, Beaker
Chemicals: Spermaceti, White Wax, Mineral Oil, Sodium tetraborate
Procedure: (Fusion Method)
1. Reduce the cetyl esters wax and the white wax to small pieces.
2. Melt the cetyl esters wax and white wax together in the Ointment Melting Apparatus.
NOTE: boiling wax is extremely flammable. Do not bring the wax to a boil.
3. Once the waxes are melted, add the mineral oil.
4. Continue heating until the temperature of the mixture reaches 70°C; maintain at 70°C for 5 minutes. (Oil phase)
5. In a separate beaker, dissolve the sodium tetraborate in the purified water, warmed to 70°C. (Aqueous phase)
6. Gradually add this warm solution (aqueous phase) to the melted oil mixture (oily phase)
7. Remove from heat. While the mixture is cooling, stir rapidly and continuously until it has congealed. Otherwise the phases will separate.

Characterization of the Vanishing cream containing drug:

1- Drug content:
The amount of drug in cream will be determined by taking 100 mg of the cream formulation and dissolve it in 10 mL of methanol after that it will be filtrated. In addition, it will be analyzed the content of Drug spectrophotometrically using (UV-VIS) at specific ?max.
2- Irritation to skin:
In this test, the cream formulation will be applied on four healthy volunteers which they should not have any sensitivity to drug. They will inform about the nature of formulation and obtain a written approval from them about the irritation effect of the formulated cream.
3- homogeneity test:
Cream homogeneity will have tested by visual appearance of the cream. Moreover, will pressed a small quantity of cream between the fingers (thumb ; index), and noticing the uniformity of formulation .
4- pH evaluation:
The cream pH value will have measured by a digital pH meter. The rang of skin pH is = (4.5 – 6) and the average pH is = 5.5, so the pH of formulation will use should close to this range.
5-In vitro release:
cellophane membrane was stretched over the end of an open-ended glass tube and made water tight using a rubber band. The tube will be immersed vertically in a 100-mL beaker containing 50 mL of buffer (pH 5.5) maintained in a thermostatically controlled shaker, 50 stroke/min maintained at 37.0±1.0°C (WiseBath, WSB-45 DAIHAN Scientific Co., Ltd, Korea).
The formulation (1 g equivalent to 50 mg) will be placed into the glass tube. At predetermined time intervals for up to 24 h, 5 mL aliquots of the release medium will be withdrawn for analysis and replaced with equal volume of release medium and buffer, at the same temperature to maintain constant volume. The absorbance of the collected samples will be measured spectrophotometrically at specific ?max.

6-Anti-fungal studies:
The antifungal action for formula will be studied using different strains of fungi by agar well-diffusion method. The inhibition zones for all formulae were compared with knwon standard antifungal.
7-physical and chemical Stability:
Physical stability will be checked by storage the cream at room temperature = (25 °C) and at (4 °C), for one month. The physical stability will evaluate of any sedimentation and particle size determination by visual observation. Also will use spectrophotometry to determine The chemical stability of cream at different days.
Statistical analysis:
We will use SPSS to compare between antifungal activity vanishing and cold cream at 0.05 significance.

Expected results:
Formulated cream will be in shiny and pearly appearance and Easy rubbing on the skin. The drug content in the cream will be effective Suitable for use. The cream will be not irritant to the skin. The cream will be homogeneous with pH of cream will be close to skin pH. The cream will be physically and chemically stable and are suitable for anti-fungal effect.

Conclusions: date palm is a good source of nutrient with high antifungal and antibacterial activity. It can be used as a natural source for treatment of different disorders. Therefore, we expect that vanishing and cold cream will have a good activity against superficial fungal and bacterial infection in similar properties.


Viquez et al., (2018). An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro. PLOS ONE, 13(1), p.e0190210.

Assirey et al., (2015). Nutritional composition of fruit of 10 date palm (Phoenix dactylifera L.) cultivars grown in Saudi Arabia. Journal of Taibah University for Science, 9(1), pp.75-79.

Dhase et al., (2014). Formulation and Evaluation of Vanishing Herbal Cream of Crude Drugs. American Journal of Ethnomedicine, 1(5), pp.313-318.

El-Far et al., (2016). Date Palm (Phoenix dactylifera): Protection and Remedy Food. Current Trends in Nutraceuticals, 1, pp.1-10.

Essa et al, (2015). Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer?s disease. Journal of Ayurveda and Integrative Medicine, 6(2), p.111.

Farouk et al., (2018). Effect of Maturation Stages on Flavor Profile and Antioxidant Activity of Date Palm Fruits (Phoenix dactylifera) Grown in Saudi Arabia. International Journal of Pharmacology, 14(3), pp.407-414.

Grumezescu, (2017). Nano- and Microscale drug delivery systems. Matthew Deans.

Hall and Noverr, (2017). Fungal interactions with the human host: exploring the spectrum of symbiosis. Current Opinion in Microbiology, 40, pp.58-64.

Hamad et al., (2015). Metabolic Analysis of Various Date Palm Fruit (Phoenix dactylifera L.) Cultivars from Saudi Arabia to Assess Their Nutritional Quality. Molecules, 20(8), pp.13620-13641.


Ismail and Altuwairki, (2016). Chemical Composition and Antimicrobial Efficacy of Date Palm Fruit of Saudi Arabia. World Applied Sciences Journal, 34(2), pp.140-146.

Khan et al., (2018). In vivo evaluation of hypolipidemic and antioxidative effect of ‘Ajwa’ (Phoenix dactylifera L.) date seed-extract in high-fat diet-induced hyperlipidemic rat model. Biomedicine ; Pharmacotherapy, 107, pp.675-680.

Meer et al., (2017). Efficacy of Phoenix dactylifera L. (Date Palm) Creams on Healthy Skin. Cosmetics, 4(2), p.13.


Reiss et al., (2017). Pharmacology in Nursing. 2nd ed.

Sahu et al., (2016). Skin Cream as Topical Drug Delivery System: A Review. Journal of Pharmaceutical and Biological Sciences, 4(5), pp.149-154.

Stephen et al., (2018). Histological and histochemical assessements on the effect of ethanol fruit extract of Phoenix dactylifera L. (Date Palm) on cerebral cortex of lead acetate treated wistar rats. African Journal of Cellular Pathology, 10(1), pp.1-9.

Olabisi and Ojotule, (2017). Phytochemical, Proximate and Antifungal Studies on Phoenix dactylifera L. IOSR Journal of Pharmacy and Biological Sciences, 12(03), pp.78-83.