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1.0 Therapeutically active substances for dandruff (OTC) 1
1.1 Ingredients suitable for the treatment of dandruff 1
1.1.1 Bifonazole 1
1.1.2 Ciclopirox 1
1.1.3 Hydrocortisone 1
1.1.4 Ketoconazole 1
1.1.5 Miconazole 1
1.1.6 Pyrithione Zinc 1
1.1.7 Resorcinol 2
1.1.8 Salicylic acid 2
1.1.9 Selenium Sulphide 2
1.1.10 Sulphur 2
1.1.11Tars and Oils 2
1.1.12 Terbinafine HCl 3
1.2 Selection of the active ingredients for the shampoo. 3
2.0 Formulating a suitable vehicle for the chosen base. 4
2.1 Primary and Secondary Surfactant. 4
2.1.1 Types of surfactants and suitability 4
22.214.171.124 Anionic Surfactants 4
126.96.36.199 Soaps of Di/Trivalent Metals 4
188.8.131.52 Amine Soaps 4
184.108.40.206 Non ionic Surfactants 4
220.127.116.11 Amphoteric Surfactants 5
18.104.22.168 Cationic Surfactants 5
2.1.2 Surfactant Concentration 5
2.2 Viscosity Control/ Suspending Agent. 5
2.3 Suspending Agent/Wetting Agent. 6
2.4 Colour. 6
2.5 Conditioning Agents. 6
2.6 Opacifiers/ Pearlescents 6
2.7 pH adjuster 6
2.8 Preservative. 7
2.9 Fragrance. 7
2.10 Chelating agents. 7
3.0 Calculations and Aliquot Statements 8
3.1 Disodium edetate aliquot. Soluable 1-10 to 1-30 in water.1 8
3.2 Approximate buffered water to be added 8
3.3 To make the buffered solution3 8
4.0 Method 8
5.0 Packaging and Labelling 9
6.0 References 10
1.0 Therapeutically active substances for dandruff (OTC)
1.1 Ingredients suitable for the treatment of dandruff
Bifonazole is insoluble in water, and slightly soluable in dehydrated alcohol. It is an antifungal agent that inhibits the growth of Malassezia spp, indicated as a causative organism in dandruff. It is typically used in concentrations of 1%(w/w) and applied once daily for 2-4 weeks.1 Not on list of available ingredients.
Slightly soluble in water and freely soluable in dehydrated alcohol and dichloromethane. Product needs to be protected from light and packaged appropriately. Has antifungal action against Malassezia spp. and is used in concentrations of 1%(w/w) twice a week.1 Not on the list of available ingredients.
Is practically insoluble in water, 1-40 with alcohol, 1-80 with acetone. Also needs protection from light. A corticosteroid it possesses anti-inflammatory effects, would reduce inflammation associated with dandruff. Used in concentrations of 0.5-2.5% (w/v) as a lotion.1
Ketoconazole is practically insoluble in water and is sparingly soluble in alcohol. Protect from light. Formulated in concentrations of 1-2% (w/v) in shampoos. Applied twice weekly for 2-4 weeks or longer.1 Not on list of available ingredients.
Very slightly soluable in water, soluble 1-9.5 in alcohol and 1-9 with propylene glycol. Possesses polymorphism . Protect from light. An imidazole anti-fungal, miconazole inhibits the growth of Malassezia spp, helping in the treatment of dandruff. Can be used in concentrations of 2%(w/v), no dosage interval given.1 Not on list of available ingredients.
1.1.6 Pyrithione Zinc
Pyrithione Zinc has activity against bacteria and fungi. Formulated using concentrations of 1-2% (w/v). 1 Not on list of available ingredients.
Resorcinol is incompatible with ferric salts. Has a solubility of 1-1 in water , needs to be protected from light. Resorcinol has keratolytic properties and is often used with sulphur.1 No information available from Martindale regarding concentrations, though 2%(w/v) used in laboratory classes for similar conditions.2
1.1.8 Salicylic acid
Salicylic acid has solubilities of 1-460 with water, 1-15 with boiling water and 1-3 with alcohol Needs protection from light. Acts as a keratolytic, which helps to remove the flakes associated with dandruff. Also possesses antifungal properties. Concentrations typically between 2-6 % (w/v) though can vary.1 Concentrations of 2%(w/v) are used for scalp disorders in the Australian formulary and handbook 20th ed (APF 20).3
1.1.9 Selenium Sulphide
Selenium sulphide is insoluble in water and organic solvents. Used for its antifungal and anti-seborrheic properties. Concentrations of 5-10 %(w/v) are used. 5-10ml of the shampoo is used, twice per week. The shampoo should be applied, left for 2-3 minutes, rinsed then repeated each time it is used.1
Sulphur is insoluble in water and slightly soluable in water. Protect from light. It acts as a keratolytic, to improve the signs of dandruff, also possesses antifungal, antiseptic and antiparasitic properties. Up to 10% (w/v) can be used in formulations.1
1.1.11Tars and Oils
Coal tar solution is soluble in alcohol. Keratolytics, reduce the thickness of the epidermis. Also possesses antipruritic and antiseptic properties. Recommend crude tar concentrations of 1-2% (v/v) up to a maximum of 10% (v/v).1 Concentrations of 5%(v/v) using Coal Tar solution are used in the APF 20 for similar conditions.3
1.1.12 Terbinafine HCl
Very slightly soluble in water and freely soluble in dehydrated alcohol. Terbinafine needs to be protected from light. An allyamine antifungal it acts against the Malassezia spp which is responsible for the dandruff. A concentration of 1% (w/v) is indicated.1 Not on list of available ingredients.
1.2 Selection of the active ingredients for the shampoo.
Eliminating those ingredients which are not available for compounding, the list of potential active ingredients includes: hydrocortisone, resorcinol, salicylic acid, selenium sulphide, sulphur and a selection of tars and oils. Hydrocortisone will not be used as an active ingredient for the shampoo. Hydrocortisone is only indicated for the relief of any signs of inflammation associated with the dandruff; it would not be suitable for long term use. Long term effects include skin atrophy and thinning.1
Tars and Oils have a very strong odour, and will be difficult to formulate into an aesthetically pleasing shampoo. Sulphur is very hydrophobic and would require a suspending or wetting agent to aid its even distribution in the shampoo. Though both products have shown to be effective a relieving the discomfort associated with dandruff, and are often used in combination with each other and resorcinol.
Salicylic acid would have some notable interactions with some of the possible surfactants which can be used in formulating a shampoo, though is an effective keratolytic. Finally selenium sulphide, an effective anti-dandruff ingredient, also possesses difficult formulation characteristics, having poor solubility in both water and alcohol.
Chosen to formulate the Anti-Dandruff Shampoo 50mL, using Coal Tar Solution 5%v/v and Salicylic Acid 2% (w/v). The method shows salicylic acid being dissolved in ethanol first, then added to the surfactant solution (see method).
2.0 Formulating a suitable vehicle for the chosen base.
2.1 Primary and Secondary Surfactant.
Often more than one surfactant is used. This is due to each type of surfactant possessing different solubilisation properties, incompatibilities and strengths. Typically anionic surfactants are preferred for use on the scalp.4
2.1.1 Types of surfactants and suitability
22.214.171.124 Anionic Surfactants
These are low in cost, easily accessible ingredients with a high degree of cleansing activity.5
Alkali Metal Soaps, for example sodium stearate, are not suitable for products containing acids. If used in this formulation, the Salicylic acid would break down the emulsion system, resulting in less foaming and a poorer quality product. Alkali emulgents also increase the pH of the formulation, causing irritation when applied to broken skin.6 This may occur in this patient group, as they may have scratched their head due to pruritis associated with dandruff.
126.96.36.199 Soaps of Di/Trivalent Metals
For example calcium oleate, are not suitable for a shampoo formulation as they are still sensitive to acids and salts.6
Includes triethanolamine and produces an emulgents system with a pH of approximately 7.5-8. Because of this, it is suitable for application to broken skin; it also has a higher resistance to polyvalent cations. It can be disrupted by high concentrations of acids and electrolytes. In the presence of metals and light it can cause discolouration of the product.6
Sulphated and sulphonated compounds are compatible with calcium and magnesium ions, form neutral solutions and are able to tolerate wide pH ranges. It is incompatible with cations, iodine and high concentrations of salicylic acid.6
188.8.131.52 Non ionic Surfactants
These include the glycol and glycerol esters, sorbitan esters, macrogol esters and ethers, polysorbates, poloxalkols, polyvinyl alcohols and higher fatty acid alcohols.6 These are not often recommended for use in shampoos as the major surfactant.7
They can enhance the lathering quality of the anionic surfactant being used and improve the texture and rheological properties of the shampoo. 5,6,7
184.108.40.206 Amphoteric Surfactants
These are also not used as the main surfactant in a shampoo, but improve the foaming properties, viscosity and mildness of the shampoo, through their low irritant effect. 7
220.127.116.11 Cationic Surfactants
These surfactants are incompatible with anionic ingredients, and as such would be incompatible with the chosen active ingredients; causing a loss of stability within the preparation.7 Examples of these surfactants include quaternary ammonium compounds. They possess good antimicrobial activity; create a product with pH of 3-7, so this will be non-irritating to the skin.6
The recommended HBL (hydrophilic/lipophilic balance) for detergents is 13-15. Sodium lauryl sulphate (an anionic surfactant) has a HBL of 40, and glyceryl monosterate (self-emulsifying non-ionic glycerol ester) has a HBL of 5.5. Together, the required HBL can be achieved. Also, the non-ionic surfactant will help to modify the characteristics of the shampoo, and can help emulsify oily substances, such as fragrant oils.6The recommended concentration for the primary surfactant for a shampoo is 9-15% and the concentration for the secondary surfactant is 0-5%.8
2.1.2 Surfactant Concentration
Will use Sodium lauryl sulphate 15%(w/v) and glyceryl monosterate 3%(w/v). Sodium lauryl sulphate is soluble 1 in 10 of water. Glyceryl monostearate is able to be dispersed in hot water with the aid of a surfactant. 1
2.2 Viscosity Control/ Suspending Agent.
The thickness of the shampoo can be altered by the addition of sodium chloride. This needs to be done with care in surfactant systems sensitive to electrolytes.4 Natural gums can also be used, hydrocolloids need to be added with care. At this stage, would consider using sodium chloride (NaCl) as a thickening agent if necessary. Would add in quantities of 0.5%(w/v) towards the end of compounding.9 Total quantity added was 3g.
2.3 Suspending Agent/Wetting Agent.
The coal tar solution is soluable in alcohol, insoluble in water, as is the Salicylic acid. The salicylic acid was first dissolved in ethanol, then added to the surfactant solution (see method). If this proves to not be enough, TWEEN 80 1.5% is a sufficient wetting agent that is compatible with this system.2A dispersal agent was not required in the formulation, the coal tar solution and salicylic acid were adequately dispersed by the surfactants.
Coal Tar Solution will colour the final product a brown/yellow colour.1 By adding a colouring agent, consistency can be achieved between batches in manufacturing. However, due to its colour, and those available from the ingredients list, there are no additives suitable for this purpose.
2.5 Conditioning Agents.
These can be added to improve the cosmetic appeal of the product. Examples include dimethicone at concentrations of 0.1-0.5%(w/v), proteins, ceramides, panthenol and glutamic acid. Dimethicone is an example of a conditioning agent that can be used.7 It is water, ethanol and acetone insoluble, so will not be used in this formulation. Dexpanthenol is freely soluable in water and used in concentrations of 0.1-5%(w/v). It is present as a liquid but may crystallise as seen in the laboratory.1 A concentration of 1% (w/v) will be used as concentrations closer to 5 %(w/v) can cause irritation.1,10
2.6 Opacifiers/ Pearlescents
These can be added to improve the physical appearance of the product. This involves addition of long chain fatty alcohols, latex opacifiers to name two. Can be a difficult process to undertake, and has been replaced by the addition of pearl extracts.4,7
2.7 pH adjuster
All shampoos are required to have the pH adjusted to between 5.6 -6.2 to suit the conditions of the scalp.7 This can be achieved by adding citric acid to lower the pH or adding sodium hydroxide to increase the pH.11 This is done after all the ingredients are added to the formulation. In the laboratory, there is no pH measuring equipment.
To overcome this, made a buffered solution at pH 6.2 using citric acid monohydrate, sodium citrate, sodium chloride and purified water, freshly boiled and cooled. (see calculations).
Used the buffered water in preparing the aliquots, the dissolutions and to make to volume, in place of the purified water (fbc) in the original formulation.
To ensure the stability of the product over its shelf life and prevent microbial contamination, a preservative should be added. A possible preservative would be phenoxyethanol 1%(v/v) or%( w/v). However its activity is reduced by non-ionic surfactants so this would not be suitable, as is chlorocresol, hydroxybenzoates.1 As the system contains anionic surfactants, preservatives such as benzalkonium chloride would be incompatible.2 Boric acid has no incompatibilities with non-ionic surfactants, nor is its activity reduced by it, it is however volatile in steam. Has been used in concentrations of 1.22%(w/v).1
This is to improve the patient acceptance of the product. Coal tar has a characteristic odour, this can be overcome by the addition of a fragrant oil. Sandalwood would have a suitable profile to help disguise the smell of the product, and ensure consistency between batches. Also used will be Pine Oil sylvestine on recommendation by Jane O’Callaghan, as it complements and disguises the smell of the coal tar solution. A recommended amount of fragrance is 0.1-2 %( v/v), will use 1 %( v/v).4 Measured via drops where 0.5mL = 10 drops.
2.10 Chelating agents.
These are incorporated to prevent any liberated or excess metal ions interfering with the surfactant system. It also prevents the formation of insoluble salt complexes and helps prevent degradation of the products.4 The Pharmaceutical Codex lists citric acid as a chelating agent, it forms complexes with metal ions at a concentration of 0.005-0.01%(w/v).12 Has a solubility of 1in 0.5 of water and 1-2 of alcohol.1 Another chelating agent is disodium edentate, which is soluble in water. 1 This is used in concentrations of 0.05-0.1%(w/v).13 It is a white crystalline powder that is insoluble in water.1
3.0 Calculations and Aliquot Statements
3.1 Disodium edetate aliquot. Soluable 1-10 to 1-30 in water.1
100 mg of disodium edetate is dissolved up to 5mL with buffered purified water(fbc).
50mg of disodium edetate is in 2.5mL of the aliquot.
3.2 Approximate buffered water to be added
50-2.5-7.5-5-0.5-0.5= 34mL (plus 3.16g of solid approx.), use 30mL to start with.
3.3 To make the buffered solution3
Need 6.2mL of 1.1%(w/v) of citric acid monohydrate
-made via 110mg of citric acid monohydrate dissolved up to 10mL with purified water (fbc)
Need 93.8mL of 1.5%(w/v) of sodium citrate
-made via 1.5g of sodium citrate dissolved up to 100mL with purified water (fbc)
Need 0.47g of sodium chloride.
Discarded excess solutions, made a total of 100mL of buffered solution of pH 6.2
1. Prepared the buffered water.
2. Prepared the disodium edetate aliquot.
3. Dissolved 1g of Salicylic acid in 5ml of Ethanol (90%v/v), using bakelite spatula to weigh.
4. Measured 7.5gof Sodium lauryl sulphate and weighed 1.5g of glyceryl monostearate.
5. Heated 25mL of buffered purified water (fbc) in a beaker to approx 70°C then added the sodium lauryl sulphate and glyceryl monostearate. Removed from heat and stirred to combine.
6. Added the Salicylic acid and ethanol mixture and stirred.
7. Added 610 mg of boric acid and stirred (careful to make sure contents to hot as may be volatile in steam).
8. Added the Disodium edetate aliquot, the 100mg of dexpanthenol, 10 drops of sandalwood oil and 10 drops of pine oil sylvestine, stirring with each addition.
9. Added the 2.5mL of Coal tar solution, stirred.
10. Check the viscosity of the shampoo. If not viscous enough at this stage, added sodium chloride in amounts of 250mg, stirring to dissolve. Total amount added was 3g.
11. Product too thick to strain. Calibrated the bottle to 50mL. Transferred product to the bottle with pump lid, made to volume with buffered purified water and labelled.
5.0 Packaging and Labelling
Packed the shampoo into a blue bottle, which has a pump dispenser. The coloured bottle will help to protect the contents from light and increase its stability.
Contains: Coal Tar Solution 5%v/v, Salicylic Acid 2% w/v, Sandalwood Oil 1%v/v, Pine Oil Syvestine 1%v/v
Danelle Shaw Pty. Ltd.
50 Hayman Rd,
Store below 25°C. Protect from light.
Batch: A1317082009 Exp: AUG 2011
Directions for use: Apply to the hair; work into lather with water. Leave for 2 minutes then rinse. Repeat if desired. Use twice weekly. If comes into contact with eyes, rinse immediately. May discolour bleached or blonde hair. May stain clothing.
Controls flaking, itching and leaves hair feeling smooth and silky. Formulated with essential oils to nourish and refresh.
1. Name of the product: SalCoal Anti-Dandruff Shampoo
2.”Professionale”: make the product appealing.
3. Product size and AustL number: listed medicine, patient assured of a good quality product that is tested for safety.
4. Brief description of the product and its use. “Controls flaking, itching and leaves hair feeling smooth and silky. Formulated with essential oils to nourish and refresh.”
5. Directions for use and safety concerns. “Directions for use: Apply to the hair; work into lather with water. Leave for 2 minutes then rinse. Repeat if desired. Use twice weekly. If comes into contact with eyes, rinse immediately. May discolour bleached or blonde hair. May stain clothing.”
6. List of active and mentioned ingredients. Also mentioned are storage conditions. “Contains: Coal Tar Solution 5%v/v, Salicylic Acid 2% w/v, Sandalwood Oil 1%v/v, Pine Oil Syvestine 1%v/v. Store below 25°C. Protect from light.”
7. Supplier details, batch number and expiry date. Supplied By: Danelle Shaw Pty. Ltd. 50 Hayman Rd, Bentley WA. Batch Number: A1317082009 Expiry Aug 2011.
6.0 References Weetman SC Editor. Martindale: The Complete Drug Reference 35. [book on the internet] 2009 [cited 2009 Aug 10]. Available from: http://www.medicinescomplete.com.dbgw .lis.curtin.edu.au
Kinsella S. Compounding tutorial 1: cream formulations[lecture]. Perth (WA): Curtin University of Technology; 2009.
Pharmaceutical Society of Australia. Australian pharmaceutical formulary and handbook. 20th ed. Curtin, ACT: The Pharmaceutical Society of Australia;2006. p 27-42,353
Bouillon C. Shampoos. Dermatol Clin. 1996;14:113-24.
Mitsui T. New Cosmetic Science. [book on the internet] 1997 [cited 2009 Aug 10]. Available from: http://curtin.eblib.com.au.dbgw.lis.curtin.edu.au/EBLWeb/patron/