Dandruff and Chemo-Antidandruff Agents

 

Sushant Sharma1, Minakshi Shroff1*, Yashwant Swarnakar2, Mamta Singh1 and Ashish Pandey1

1Institute of Pharmacy, Chhatauna, Mandir Hasaud, RITEE, Raipur, Chhattisgarh, India

.2Shri Sankaracharya Institute of Pharmaceutical Sciences, Chhattisgarh, India.

*Corresponding Author E-mail: mahishroff@gmail.com

 

ABSTRACT

Dandruff is often seen in the primary care setting as well as in the dermatology field. In this article, we review the mostly used drugs for treating dandruff and compare their efficacy in eradicating the symptoms of dryness and flaking of the scalp, along with providing relief of associated pruritus. Examples of such agents include keratolytics, regulators of keratinization, antimicrobials, and naturopathic therapies. We examine their mechanisms of action and their efficacy in treating dandruff.

 

KEYWORDS: Dandruff, Antidandruff agent, Dermatology.

 


INTRODUCTION:

Term   “Dandruff”- pityrasis, meaning bran-like epidermal scaling (Greek pityron:  bran-like) was introduced into dermatological vocabulary by Galen. [1] Disease constitutes a vary widespread problem, present in more than a half of population of Caucasian origin.[2] .Although most commonly it is a problem of just aesthetic nature chronic character of this condition and tendency to relapse makes it troublesome and difficult to cope for people suffering from this condition.

 

Causative organism:

a)      Pityriasis simplex

b)      Pityriasis steatoids

c)      Malassezia furfur

d)      M. restricta

e)      M. Globosa

 

Types of dandruff:

Two types of dandruff can occurs – common (dry) or oily dandruff. [3]

 

Common (dry) Dandruff: (Pityriasis simplex capiliti S. sicca, furfuracea) is characterised by excessive formation of minute scales of whitegreyish or ashen colour, accumulating on the scalp area. These bran-like scales are first localised in the middle of the scalp area and then spread towards, parietal, frontal and occipital areas.[3]

 

Scales visible on the scalp are separated cells of keratinised layer, whose renewal cycle is pathologically shortened (even to 7 days, with the normal equalling 28 days). Hairs in this type of dandruff are not changed and no hair loss is observed.

 

In the epidermis of people suffering from common dandruff histopathology analysis reveals characteristic intervals of parakeratosis foci, raised mitotic index of corneocytes and peeling in the form of multicellular aggregates; there is no actual inflammatory status of the proper skin.[4]

 

Oily Dandruff:  (Pityriasis steatoides ), being just the form of dandruff arising on the scalp skin with varied intensity of sebum production. It appears most often in young men following puberty (aged between 18 and 24). On the skin of the scalp area inflammation of various intensity then develops, constituting the basis for basis for fragile, oily scales (pityraisis oleosa) of dirty yellow colour, which can be associated with pruritus of various intensity.[3]

 

Severity of Dandruff:

Sometimes, dandruff can be extreme and difficult to treat. Extreme dandruff is often causes by a condition called “seborrheic dermatitis” which has a build-up of skin cells in scaly patches on the scalp. In babies, “seborrheic dermatitis” is referred to as “cradle cap.”

 

Some medical causes for extreme dandruff are:

·        Seborrheic dermatitis: This condition is distinguished by oily and red skin and can show up on the scalp as well as other oily parts of the body. On the scalp, dead skin cells will form a crusty layer appearing yellow or white in color. These dead skin cells may attach to the hair follicles. In babies and toddlers, it is commonly referred to as “cradle cap.”

·        Psoriasis: Dead skin cells do not shed and leave the skin surface as they should. The result is a buildup of dead, hard skin forming scales.

·        Eczema: Sensitive skin with dry red rash. Eczema, if located on the scalp, can make the scalp very sensitive and itchy.

·        Malassezia: A yeast-like fungus, malassezia occurs on most adult’s scalps without causing any problems. In some cases, the malassezia may grow out of control and being to feed on the oil secretions by the hair follicles. This can cause excess dead skin cells to mix with the oil and form clumps which are very visible on clothing.

·        In severe cases of dandruff, for which the medical term is seborrheic dermatitis or seborrhea, some hair follicles could be damaged or destroyed. But there is no evidence in the medical journals that baldness is caused by ordinary dandruff. Dandruff and baldness often occur together though. Many people assume from this that one is caused by the other. It's a false assumption.

 

Etiology of Dandruff:

The aetiology of dandruff, being the form of seborrhoeic dermatitis, is not unequivocally established Many factors are usually listed, described as endogenous and exogenous. Researchers include the following into the first group

 

1. Endogenous: (i) Immunological abnormalities, related to humoral and cell immunity, proved by associated severe sebhorrhoeic dermatitis often observed in subjects infected with HIV or suffering from AIDS; disorder is present in a significant proportion of this group of patients (34-83%);[5]

(ii) Neurological abnormalities (during depression, also in case of Parkinson disease),

 

2.  Exogenous: (i) Life style (incorrect skin care , micro trauma and stress ),  (ii)Diet factor (poor nutrition, alcoholism) (iii)Environmental factors (environmental pollution and climate).[5,6,7]

 

Seborrhoeic dermatitis can also be associated with the presence of other disease including: pancreatitis, HVC infection, neoplasm and also genetic abnormalities (for example down syndrome, hailey-hailey disease).[5]

 

a)      Microbial etiology of dandruff

There could be several etiopathologic pathways with complex mechanisms, which may cause dandruff. The role of lipophilic yeast belonging to the genus malassezia was widely accepted to play a role in dandruff way back in 1846.[12,14] Eichstedt was the first to recognize the presence  of this fungus in the disease pityriasis versicolor.[8,15] The scalp form as biocenose for various organisms such as Staphylococci spp., Propionibacterium spp., and Malassezia spp.,[16,17] The density of these organisms varies from 10 3 to 10 5 organisms per mm 2 . During dandruff, the levels of Malassezia increase by 1.5 to 2 times its normal level. It has been debated that the quantitative microbial assessment of all kinds does not indicate the role of yeast; the abundance that might have been proportional to the volume of scales which it colonizes or be responsible for the altered desquamation. Interestingly, the specific relationship between a species of Malassezia appears to be the strategy for treating dandruff.


In response to the use of antifungal preparations, population of Malassezia reduces, but the bacterial population is seldom affected. After withdrawal of treatment, the clinical situation recurs and Malassezia population increases to the initial level. Another interesting aspect on the microbial cause of dandruff is the positive treatment response of dandruff to various steroids. Steroids are known to suppress the immune flare-up and the microbe will advantageously utilize the immune suppressed opportunity. But the good treatment response and prolonged remission period with steroid treatment raises a doubt on the microbial cause of dandruff. Whether the increased Malassezia count is the result of abundant scales or abundant scales is due to the increased Malassezia population lack clear explanation till date.[16]
 There are seven species of Malassezia - M. globosa, M. resticta, M. obtuse, M. sloofiae, M. sympodialis, M. furfur and M. pachydermatis, which have been recognized in dandruff formation.[18]  However, none of the species of Malssezia have fulfilled the Koch's postulates as a pathogen of dandruff till date.

 

b)      Non-microbial etiopathology of dandruff:

The non-microbial cause for dandruff is well established. Excessive exposure to sunlight is known to cause desquamation of the scalp.[19,20] Minimal irritation of scalp due to over shampooing, frequent combing, use of certain cosmetic products, dusts and dirt also, to some extent, cause dandruff. However, there is no sufficient experimental evidence to the above assumptions.[21]

 

Detail discussion: Dandruff:

Pathophysiology:

Even today, the debate on whether dandruff has to be treated as a disease or a disorder continues. In the physiological spectrum of scaling, about 487,000cells/sq cm get released normally after detergent treatment and this number goes up to 800,000/sq cm during dandruff and seborrhoeic dermatitis.[8] However, dandruff is non-inflammatory in nature. The real cause for dandruff formation from the normal physiological spectrum of scaling is yet to be understood.

 

The spectrum of dandruff is difficult to define because its blurs with seborrhoeic dermatitis and some other scaly conditions. The inflammation and extension of scaling outside the scalp excluded the diagnosis of dandruff from seborrhoeic dermatitis.[9] However, many reports suggest a clear link between the two clinical entities – the mildest form of the clinical presentation of seborrhoeic dermatitis as dandruff, where the inflammation is minimal and remain subclinical. Histological examination reveals the scattered presence of lymphoid cells and squirting capillaries in the papillary dermis with hints of spongiosis and focal parakeratosis.[10,11]

 

Conceptually, dandruff is a dander and represents nothing more than physiological scaling.[12] Hence it is believed that physiological scaling process requires more cosmetic management. The response to treatment is commonly swift, but transient. On the contrary, seborrhoeic dermatitis is obviously more inflammatory in nature extending outside the limit of the scalp surface.[8]

 

Composition:

Dandruff scale is a cluster of corneocytes, which have retained a large degree of cohesion with one another and detach as such from the surface of the stratum corneum. The size and abundance of scales are heterogeneous from one site to another and over time. Parakeratotic cells often make up part of dandruff. Their numbers are related to the severity of the clinical manifestations, which may also be influenced by seborrhea.[13]

 

 

Causes:

The most common cause of dandruff is the fungus Malassezia furfur (previously known as Pityrosporum ovale). This fungus is found naturally on the skin surface of both healthy people and those with dandruff. The fungus feeds off of sebum and is consequently found most on skin areas with many sebaceous glands: on the scalp, face and upper part of the body. When Malassezia furfur grows too rapidly, the natural renewal of cells is disturbed and dandruff appears with itching. Mild dandruff may be caused by overactive sebaceous glands which are triggered by hormonal imbalance or stress.

 

Other causative factors include family history, food allergies, excessive perspiration, use of alkaline soaps and yeast infections. Even the season of the year can contribute to the problem. Cold, dry winters are notorious for bringing on dandruff or making it worse. Symptoms of dandruff can also be aggravated by exposure to dust, UV light, harsh shampoos and hair dyes. [22]

 

Nature:

Research suggests that dandruff is a subclinical inflammatory scalp disorder resulting in a disruption of connection between the cells within the top layer of the skin. This abnormality may only be episodic, but can also be a permanent condition. Often such kind of mild scalp inflammation is accompanied by varying degrees of pruritus. The dandruff scale is an aggregate of horny skin cells which have retained a large degree of cohesion with each other and become detached in clusters from the surface of the upper layer of the skin. The size of the scales is heterogeneous at a given site of the scalp, and their abundance may vary from one site to another and over time. [23]

 

Role of corneocytes in dandruff:

Both in dandruff and seborrhoeic dermatitis, the population of malassezia is not uniform throughout the skin surface and inside the stratum corneum.[10,24] Clumpy adherence of the yeast is seen in some corneocytes, whereas other corneocytes in the neighborhood region harbor few of these yeast. It is presumed that perhaps the Malassezia binding site may differ in corneocytes. Another postulate is the natural antifungal peptides of the innate immunity to the above cause. The colonization of the yeast boosts the expression of β-defensin-2 by keratinocytes.[25] In dandruff, their expression could be impaired at some sites where the abundance of Malassezia is more. It is known that Malassezia has antigenic and pro-inflammatory properties stimulating both innate and acquired immune response and neuro immune sensorial response as well.[26]  In dandruff, the immune response is not altered.


The Malassezia - corneocyte hypothesis still leaves some doubt. It does not explain why scaling at low grade (2-5 mg/cm scalp/2 days) with low parakeratotic index persist despite dandruff being resolved and Malassezia largely removed.[8]  It is hypothesized that the antifungal agents may not be able to eradicate deep-seated yeasts allowing a minimal inflammatory reaction to be maintained or the anti inflammatory activity claimed in the antidandruff agents is not effective enough in vivo.[27] The adverse reaction such as irritant dermatitis or contact allergic dermatitis may be provoked by the treatment agents also. [28]

 

 

Role of Lipids:

Human scalp is very androgen sensitive and sebum rich.[8,29] The sebum forms an ideal nutrient in the biocenose and sebum formation starts with the onset of puberty. However, sebum excretion rate in dandruff infected and non-infected subjects was found to be same. Many subjects with oily scalp did not show dandruff as well.[30] This clearly shows that lipids may facilitate to some extent but not be the primary cause. Many authors presume that host susceptibility factors play a major role in dandruff formation. It is already known that skin surface lipids influence the transient form of M. orbiculare and M. furfur. It is also known that dandruff affects people at puberty and middle age more than elderly subjects.[12] In vitro findings suggest that cholesterol and cholesterol esters induce hyphal formation in Malassezia. However, the quantitative or qualitative difference in skin lipids in pityriasis infected and non-infected subjects doesn't seem to vary very significantly.

 

Many authors have considered that host susceptibility factors account more for dandruff than the lipase activity of the microbe. Although there is sufficient evidence on the growth promotion role of various lipids on Malassezia, a clear-cut correlation on the quantitative or qualitative profile of lipids in the infected and control subjects is lacking.[31] An in vitro study using Tween 80, a water soluble ester of low chain (C17) fatty acids, which can serve as substrate both for lipase and esterase reveal that growth inhibition was observed with the addition of esterase inhibitors such as di-isopropyl fluorophosphates or quinine while the lipase inhibitors sodium fluoride seldom affects the growth. Studies on the growth supporting ability of various water-soluble triglycerides such as glyceryl esters of long chain fatty acids triolein (C17) and short chain tributyrin (C4) showed that long chain fatty acids have growth-supporting ability.[31]

 

Dandruff and hair:

The severity of dandruff ranges from to severe among subjects, possibly the scales may be trapped in the mesh of crowded terminal hair prohibiting them from being lost. This dandruff-hair relationship may, in part, explain the absence of dandruff in bald pates and hairless or shaved sites and in regions of vellus hairs. The presence of dandruff may precede or accompany telogen effluvium.[32] It may also exacerbate androgenetic alopecia. On a two-day survey, it has been observed that about 100-300 numbers of hairs were shed in dandruff sufferers instead of 50 – 100 in normal subjects.[10]

 

In some cases of dandruff, hair shedding may be a result of alterations in the teloptosis process (exogen phase) and hair eclipse phenomenon. Interestingly, some of the antidandruff compounds, especially ketoconazole, may limit the progression of androgenic alopecia.[32,33,34]

 

ABO blood groups and dandruff:

Another interesting study linking the role of ABO blood group carriage rate of dandruff reveals that ABO blood group system does not play a role either in the prevalence or chronicity of dandruff.[35]  The role of ABO blood group in certain other fungal skin diseases is well established. The cross reactivity between the fungal cell wall protein and the isoantign of ABO blood groups is presumed to be the cause for the selective susceptibility of certain blood group subjects to fungal diseases. [36]

Changing perspectives:

Many attempts have been made to understand the pathogenesis and pathogenecity of dandruff. De Angelis  et al[37] ,give an interesting result - that M. restricta and M. globosa are the most prevalent in dandruff affected population than M. furfur. They have also shown, concomitant with the elimination of these organisms, the remission of dandruff symptoms in all the cases they have studied. They hypothesized that species' specificity and specific targeting is required to combat dandruff. However, an earlier study of Faergemann in 2002[38] showed the presence of M. restricta to a very less extent in dandruff affected population.


A further twist in the understanding of the role of M.restricta in dandruff came with studies of Sugita et al.[39] The genotype analysis of M. restricta revealed that only a specific genotype of the organism plays a significant role in atopic dermatitis and dandruff although the prevalence of the organism is universal. Despite the elusive and idiopathic nature of dandruff, it remains a problem for great commercial exploitation.

 

Treatment of Dandruff:

Therapy of dandruff may include three different basic principles

 

1. Principles of Dandruff Treatment:

(i) Symptomatic Treatment:

·                  Reduction of itching (pruritus)

·                  Reduction of scale formation (desquamation) Symptomatic treatment is often achieved by frequent hair washing with normal shampoo that does not contain any active ingredients. The effect is due to the surfactants in the shampoo but is usually only transient.

 

(ii) Causal Treatment:

·                  Reduction of Malassezia yeast

·                  Reduction of inflammation of the scalp

·                  Reduction of proliferation of skin cells

 

Causal treatment includes the repeated use of anti-squamolytic agents and anti-fungal agents. Anti-squamolytic agents include salicylic acid and coal tar which both reduce skin proliferation and promote desquamation. The most frequent antifungal agents are tea tree oil, piroctone olamine, zinc pyrithione, selenium disulphide, terbafine, and ketoconazole. All are active against yeast and reduce inflammation of the scalp.

 

(iii) Prevention of Relapse:

Prevention of regrowth of Malassezia yeast Regrowth of yeast on the scalp can be avoided by using of anti-fungal shampoos at regular intervals (e.g. 1-2 times a month).

 

Depending on the active agent used and the frequency of hair shampooing the success rate of these treatments are usually high. Frequent cleaning of the scalp with a standard shampoo containing just surfactants but no active ingredients is often sufficient to control minimal dandruff. In fact, the surfactants in hair shampoos are themselves therapeutic agents since they detach the superficial horny skin cells including the microorganisms inhabiting them. Surfactants can therefore be regarded as dispersing agents for fine dandruff. However, although surfactants provide immediate results, the effect remains weak to moderate and is only transient. This effect of surfactants can further be increased by using ‘harsher’ shampoos (change from a ‘mild’ to a ‘normal’ hair shampoo) which are able to eliminate dandruff almost completely. However, shampoos with harsher surfactants are more irritant resulting in a contrary effect since they promote inflammation of the skin. A vicious circle is then established. The addition of squamolytic agents such as salicylic acid or tar derivatives have been advocated and used very successfully. Coal tar is most frequently being used. As an added bonus, coal tar has a natural conditioning effect, which adds softness and shine without adding the oils contained in conditioning products. A vital stage in dandruff treatment was reached with the use of antifungal agents including zinc pyrithione, piroctone olamine, selenium disulphide, terbafine, and ketoconazole. Ketoconazole has demonstrated its superiority in terms of antifungal activity against Malassezia. It has been shown that tea tree oil is active against a wide range of microorganisms including Malassezia and thus may also be effective in dandruff. In fact, a study has shown that the use of a 5% tea tree oil shampoo resulted in a 41% improvement in the dandruff severity core compared with 11% in the placebo group. Significant improvements were also found in the itchiness and greasiness.[23]

 

Chemo-Antidandruff agents:

Antifungal drugs (such as ketoconazole) are often found in anti-dandruff shampoos. The antifungal drugs inhibit the yeast Malassezia globosa which encourages seborrhoeic dermatitis and tinea versicolor.

 

1.Classification of Antidandruff Agent:

1)      Salicylic acid

2)      Sulphur

3)      Zinc pyrithione

4)      Selenium sulphide

5)      Coal tar

6)      Steroid

a.       Eg: Clobetasol propionate

7)      Imidazole Antidandruff agent

a.       Eg: Ketoconazole, Fluconazole, Climbazole, Econazole, Metronidazole

8)      Hydroxypyridones

a.       Eg: Ciclopirox olamine, Piroctone Olamine

9)      Povidone iodine

 

(i) Salicylic Acid:

Salicylic acid is a beta-hydroxy acid keratolytic agent that is useful in removing scaly, hyperkeratotic skin; it decreases cellto- cell adhesion between corneocytes. Although the mechanism of action of organic acids is unclear, it may involve the release of desmogleins and the disintegration of desmosomes. Activation of an endogenous pathway, responsible for normal cell separation, may also be involved, but this hypothesis has not been confirmed.[40]

 

Keratolytic Effect of salicylic Acid:

One of the major properties of salicylic acid is its ability to remove skin cells of the most upper layer of the skin, the stratum corneum. This keratolytic effect is dependent on the concentration of salicylic acid used in a cream. For example, at a concentration of 10 - 15% salicylic acid shows a keratolytic effect already after 2 or 3 days. At 5% and 1% desquamation of skin cells is seen after 7 and 10 days, respectively. Hence, salicylic acid is widely used as major ingredient for peelings or other exfoliant or abrasive skin treatments. Such peeling products contain salicylic acid usually at concentrations between 0.5 - 3%. Whereas the upper limit of 20% of is applied only in dermatological (prescription) products, the use of salicylic acid at this level has also been recommended for face masks. For anti-warts products salicylic acid is usually used between 12 - 40%. Besides removing old cells and horny debris from the skin, keratolysis has also the advantage that it facilitates the penetration of other active ingredients into the skin. Salicylic acid is therefore often added to skin care products that contain active ingredients in order to increase their absorption and efficacy.it still shows significant effects and is therefore widely used in anti-inflammatory creams and ointments.[41]

 

It can also be prepared by the hydrolysis of Aspirin (acetylsalicylic acid)  or methyl salicylate (Oil of Wintergreen) with a strong acid or base.[42]

 

Structure:

 

(ii) Sulphur:

Sulfur is a yellow, nonmetallic element with both keratolytic and antimicrobial properties. The keratolytic effect is thought to be mediated by the reaction between the sulfur and the cysteine in keratinocytes, whereas the antimicrobial effect may depend on the conversion of sulfur to pentathionic acid by normal skin flora or keratinocytes.[43,44] The keratolytic properties may promote fungal shedding from the stratum corneum.[45] The precise mechanism of action is still unknown.[46] Leyden et al. studied the combination of 2% sulfur and 2% salicylic acid in a shampoo base (e.g., Sebulex, Westwood Squibb) in a double-blind, controlled trial using both clinical assessment of scaling and corneocyte counts.[47] They observed significantly greater and earlier reductions in both the degree of scaling and in corneocyte counts in subjects using the 2% sulfur/2% salicylic acid combination than in those using either the active ingredient alone or the shampoo vehicle.

Sulfur in the solid state ordinarily exists as cyclic crown-shaped S8 molecules. Sulfur is corrosive to many metals via the process called tarnishing.[48]

 

(iii) Zinc:

It is thought that zinc pyrithione (ZPT) heals the scalp by normalizing epithelial keratinization, sebum production, or both. Some studies have also shown a significant reduction in the numbers of yeast organisms after the application of zinc pyrithione.[49,50] A study by Warner et al. demonstrated a dramatic reduction of the structural abnormalities found in dandruff with the use of zinc pyrithione shampoo[51] the number of Malassezia organisms decreased, parakeratosis was eliminated, and corneocyte lipid inclusions were diminished. Therefore, normalization of the stratum corneum ultrastructure by zinc pyrithione is thought to be secondary to the correction of the pathology in the living epidermal layers.

 

Mechanism of action:

Its antifungal effect is proposed to derive from its ability to disrupt membrane transport by blocking the proton pump energizes the transport mechanism. Experiments have suggested that fungi are capable of inactivating pyrithione in low concentrations[52]

 

Structure:

 

Marketed preparation: DANTUFF-Z-48%

 

(iv) Selenium Sulphide:

It is thought that selenium sulphide controls dandruff via its anti-Pityrosporum effect rather than by its anti-proliferative effect;[53]however, it also significantly reduces the rate of cell turnover. It has anti-seborrheic properties and appears to produce a cytostatic effect on cells of the epidermis and follicular epithelium. Selenium sulphide is available over the counter as a 1% shampoo and by prescription only as 2.25% (Selseb, Doak Dermatologics) and 2.5% shampoos. A study by Danby et al. compared ketoconazole 2% shampoo (e.g., Nizoral, McNeil Consumer)with selenium sulphide 2.5% shampoo (e.g., Selsun) in 246 patients with moderate-to-severe dandruff in a randomized, double-blind, placebo-controlled trial.[54] Both ketoconazole and selenium sulphide were effective in treating dandruff, but ketoconazole was better tolerated because of its fewer adverse drug effects (ADEs). Excessive oiliness of the scalp is a significant ADE for many patients who regularly use selenium sulphide to control dandruff. Pierard-Franchimont and Pierard studied the sebum excretion rate in 52 men using anti-dandruff treatments.[55] At the end of the five-week treatment period, the rates of sebum excretion showed an average increase of 58% with the use of selenium sulphide, an increase of 3% with ketoconazole, and an increase of  5% with econazole (e.g., Spectazole, OrthoNeutrogena). Rapaport compared the anti-dandruff efficacy of four shampoos in 199 patients: selenium sulphide 1% (Selsun Blue, Chattem, Inc.), zinc pyrithione 1% (Head and Shoulders, Procter and Gamble) coal tar extract 5% (Tegrin, GlaxoSmithKline), and a shampoo vehicle (Flex, Revlon).[56] Subjects using Selsun Blue experienced significantly greater improvement of symptoms than did any of the other groups. Van Cutsem et al. compared the in vitro antifungal activity of ketoconazole 2%, selenium sulphide 2.5%, and zinc pyrithione 1% and 2% against M. furfur in guinea pigs.[57] Ketoconazole was found to be the most effective for reducing M. fufur counts, but results with selenium sulphide and 1% and 2% zinc pyrithione were comparable. The anti-dandruff effects of ketoconazole were superior to those of selenium sulphide and zinc pyrithione.[57,58] Selseb (Doak) is a prescription-only combination of selenium sulphide 2.25% in a urea vehicle with zinc pyrithione.

 

Uses: Selenium sulfide is used as an ingredient in antidandruff shampoos and as a constituent of fungicides (ATSDR 1996). Prescription strength and nonprescription strength medications contain 2.5% and 1% selenium sulfide, respectively (MEDLINEplus 2001). Approximately 440 lb of selenium sulfide were consumed for pharmaceutical and cosmetic products in the early 1970s (IARC 1975).[59]

 

Structure:

 

(v) Tar:

Although tars have been classically used to treat psoriasis, they offer an effective therapy option in treating dandruff as well. Problems with staining, odour, and messiness in its application make tar a second-line therapy for most patients. Tar gels contain coal tar extract, and they are generally less messy and smelly than tar itself. Tar shampoos work through antiproliferative and cytostatic effects, although definitive analyses are difficult because of the large number of biologically active components in coal tar products. Tar products disperse scales, which may reduce Malassezia colonization.[60] In the mouse model, topical application of tar suppresses epidermal DNA synthesis. pierard-Franchimont et al. conducted a randomized, doubleblind study to compare two groups of 30 volunteers with moderate- to-marked dandruff using either a non-tar shampoo (2% salicylic acid, 0.75% piroctone olamine, and 0.5% elubiol) or 0.5% coal tar shampoo.[61]They observed a significantly greater reduction of Malassezia species counts in the non-tar group; however, subjects in both groups experienced clinical improvement.

 

(vi) Steroids:

The pharmacokinetic properties of topical corticosteroids depend on the structure of the agent, the vehicle, and the skin onto which it is applied. Topical corticosteroids work via their anti-inflammatory and antiproliferative effects. On the scalp, lotions or solutions having moderate-to-high potency are typically used. Clobetasol propionate 0.05% (Clobex, GlaxoSmithKline) is available in a shampoo form. Although no studies currently exist regarding the efficacy of steroid shampoos in managing dandruff, the efficacy of topical steroid applications has long proved effective in treating the condition.[62] Topical steroids are often used in combination with other dandruff treatments such as antifungal agents.

 

Structure:

 

(vii) Imidazole Antifungal Agents:

Imidazole topical antifungals such as ketoconazole act by blocking the biosynthesis of ergosterol, the primary sterol derivative of the fungal cell membrane. Changes in membranepermeability caused by ergosterol depletion are incompatible with fungal growth and survival. Ketoconazole is a broad-spectrum antimycotic agent that is active against both Candida albicans and M. furfur. Of all of the imidazoles currently available, ketoconazole has become a leading contender among treatment options because of its effectiveness in treating seborrheic dermatitis. A ketoconazole 1% shampoo has been approved for over-the-counter use, and a 2% shampoo is available by prescription (Nizoral). Rare ADEs include irritation and stinging. Ketoconazole 2% shampoo has been studied extensively in more than 2,000 patients with dandruff or seborrheic dermatitis. Compared with placebo, the shampoo has been consistently more effective. In a randomized study comparing the efficacy of a four-week trial of ketoconazole 2% shampoo with zinc pyrithione 1% shampoo, Pierard-Franchimont et al. found ketoconazole to be statistically significantly superior (with subjects showing a 73% improvement) the other (a 67% improvement). [63]

 

As an antifungal, ketoconazole is structurally similar to imidazole and interferes with the fungal synthesis of ergosterol, a constituent of fungal cell membranes, as well as certain enzymes. As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM). This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol.

 

Lower doses of fluconazole,climbazole and itraconazole are required to kill fungi compared to ketoconazole, as they have been found to have a greater affinity for fungal cell membranes.[64]

 

Structure

Ketoconazole:

Marketed preparation: DANTUFF-

 

Fluconazole:

Like other imidazole- and triazole-class antifungals, fluconazole inhibits the fungal cytochrome P450 enzyme 14α-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α-methyl sterols. Fluconazole is primarily fungistatic, however may be fungicidal against certain organisms in a dose-dependent manner. It is interesting to note that, when fluconazole was in development at Pfizer, it was decided early in the process to avoid producing any chiral centers in the drug so that subsequent synthesis and purification would not encounter difficulties with enantiomer separation and associated variations in biological effect.

A number of related compounds were found to be extremely potent teratogens, and were subsequently discarded.[64]

 

 

Fluconazole:

Climbazole:

Climbazole is a topical antifungal chemical commonly used in the treatment of human fungal skin infections like dandruff and eczema. Its chemical structure and properties are similar to other fungicides like ketoconazole and miconazole

.  It is most commonly found as an active ingredient in OTC anti-dandruff and anti-fungal products, including shampoos, lotions and conditioners. It may be accompanied by other active ingredients like zinc pyrithione or triclosan
[64]

 

Climbazole (1-(4-chlorophenoxy)-3,3-dimethyl-1- (imidazole-1-yl)-2-butnone is an antifungal agent with topic and systemic action that can be incorporated in to several pharmaceutical forms. As an example we could mention climbazole shampoo which is effective against seborrhoeic dermatitis as well as pityriasis versicolor. For determination of climbazole several different analytical procedures have been described in pharmaceutical formulations: potentiometric , Spectrophotometric  and chromatographic methods. However there are no official microbiological cylinder plate assays described neither in the official codes nor in the literature to determine climbazole in shampoo. The activity (potency) of antibiotics may be demonstrated under suitable conditions by their inhibitory effect on microorganisms (US Pharmacopoeia, 2004).[65]

 

Structure:

Climbazole:

Marketed preparation: DANTUFF-C, it is an imidazole fungicide. Dantuff-C is used in shampoos and cleaners as an anti-dandruff and anti-bacterial agent. Anti-fungal (shampoo formulations) preservative, antidandruff agent in cosmetics.

 

Econazole :

Econazole:

Metronidazole:

Metronidazole, taken up by diffusion, is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up by anaerobes, it is non-enzymatically reduced by reacting with reduced ferredoxin, which is generated by pyruvate oxido-reductase. This reduction causes the production of toxic products to anaerobic cells, and allows for selective accumulation in anaerobes. The metronidazole metabolites are taken up into bacterial DNA, and form unstable molecules. This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic cells, it has relatively little effect upon human cells or aerobic bacteria.[64]

 

Structure :

 

Hydroxypyridones:

In contrast to the imidazole anti-fungals, the hydroxypyridones do not affect sterol biosynthesis; instead, they interfere with the active transport of essential macromolecule precursors, cell membrane integrity, of dermatophytes and yeasts. Ciclopirox 1% (Loprox, Medicis), a member of the hydroxypyridone family, has broad-spectrum action against dermatophytes, yeast, and fungi. Its anti-inflammatory activity has been demonstrated in human polymorphonuclear cells. This agent also inhibits prostaglandin and leukotriene synthesis. Lee et al. compared the efficacy of ketoconazole 2% shampoo (e.g., Nizoral) with ciclopirox olamine 1.5% shampoo (Stieprox, Stiefel Laboratories, not available in the U.S.) for the treatment of mild-to-moderate dandruff in 57 patients. A progressive decrease in dandruff scores was observed throughout the treatment period of both shampoos. However, the ciclopirox patients experienced a slightly increased incidence of pruritus during theand cell respiratory processes post-treatment phase. The investigators concluded that ciclopirox olamine was effective and safe for mild-to-moderate dandruff, although ketoconazole was somewhat more effective in treating the pruritus associated with dandruff. Altmeyer and Hoffman performed a double-blind, vehicle controlled, randomized study to compare the vehicle with three different concentrations of ciclopirox shampoo: 0.1%, 0.3%, and 1%.35 A total of 203 patients were enrolled in the study. Although all of the ciclopirox-treated participants tended to show improvement, the most pronounced improvement was noted in the ciclopirox 1% group. All concentrations were found to be safe and well tolerated. Ciclopirox 1% is available as a prescription medication. Combining ciclopirox olamine 1.5% with salicylic acid 3% allows better access of ciclopirox olamine to the underlying diseased area via the activity of the salicylic acid in decreasing the hyperkeratotic scale.36 A randomized, single-blind, single center trial study, sponsored by Stiefel International and conducted by PPD Development, was conducted to compare the efficacy of the combination ciclopirox olamine 1.5% and salicylic acid 3% shampoo with ketoconazole 2% shampoo (Nizoral). Both patient groups showed significant improvement in seborrheic dermatitis and dandruff, but only the ciclopirox/salicylic acid group showed significantly diminished itching. The two shampoos were comparable in their efficacy.[66]

 

Ciclopirox olamine:

In contrast to the azoles and other antimycotic drugs, the mechanism of action of ciclopirox is only poorly understood. However, loss of function of certain catalase and peroxidase enzymes has been implicated as the mechanism of action, as well as various other components of cellular metabolism. In a study conducted to further elucidate ciclopirox's mechanism, several Saccharomyces cerevisiae mutants were screened and tested. Results from interpretation of the effects of both the drug treatment and mutation suggested that ciclopirox may exert its effect by disrupting DNA repair, cell division signals and structures (mitotic spindles) as well as some elements of intracellular transport.

 

It acts by inhibiting the membrane transfer system by interrupting the Na+ K+ ATPase. It is currently being investigated as an alternative treatment to ketoconazole for seborrhoeic dermatitis as it suppresses growth of the yeast Malassezia furfur. Initial results show similar efficacy to ketoconazole with a relative increase in subjective symptom relief due to its inherent anti-inflammatory properties [64]

 

Structure: ciclopirox olamine:

 

Piroctone olamine:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-(1H)pyridinone,2-aminoethanol salt

Tonics, Dressings andother hair grooming aids.

 

Efficacy:

The scalp defends itself against micro-organisms and fungus infections. The defence system protects the scalp against all kinds of influences that it is exposed to. Sometimes this defence system becomes weakened and a certain fungus infection develops called Pityrosporum Ovale. This fungus infection causes considerable cell multiplication. The skin is no longer in a position to defend itself; the scaling becomes rapid, and starts to gather on the scalp. A superfluous cell situation mixing with skin sebum causes dandruff to be formed. People with dandruff experience itchiness of the scalp. Besides this, their problem is very often an ongoing one. Piroctone olamine is an anti-dandruff active ingredient, soothes inflamed scalp and reduces flaking. It has a specific action against Pityrosporum Ovale, the agent responsible for the production of dandruff. The anti-dandruff product containing piroctone olamine destroys the fungus infection that is responsible for the dandruff and works against the formation of new dandruff, makes the scalp stay clean, itch free and prevents the formation of new dandruff. You become free of all the inconvenience relating to dandruff. After six weeks of treatment, the scalp dandruff decreased 81.7% by using a shampoo containing 0.5% piroctone olamine, and 68.6% by a 0.5% zinc pyrithione shampoo.[67]

 

Structure:

 

Povidone iodine:

Povidone iodine is an iodophor, i.e.it is labile complex of iodine with the polyvinyl pyrollidone polymer, from which iodine is continually delivered. Only this free iodine has antimicrobial activity. in iodophors there is a complex relationship between the solution and the concentration of free iodine, so that e.g. through the dilution of a 10% solution with a rate of 1:10 more free iodine is released from the complex and the anti microbial activity is increased. Elemental iodine has very broad anti microbial spectrum against bacteria viruses. Bacterial endosperm fungi and protozoa’s are destroyed through oxidative interaction and direct iodination of biological macromolecules. However, there have been reports of certain resistant germs. Povidone iodine and their preparation are official in USP, European pharmacopoeia and are recognised as effective broad spectrum biocidal agent the invitro biocidal activity has been studied for years against bacteria, yeast, moulds, viruses, fungi, protozoa, actinomycetes and rickettsia. [68]

Structure:

 

CONCLUSION:

It is our opinion that moderate-to-severe dandruff is most effectively treated with imidazole antidandruff agent such as ketoconazole, metronidazole, sometimes in combination with a high-to-superpotent steroid solution to control inflammation. Ciclopirox is also highly effective. For mild-to-moderate dandruff, zinc pyrithion, salicylic acid, selenium sulfide or coal tar often work well and are an affordable and readily available option for patients. Many therapeutic options for dandruff are available in shampoo vehicles. These formulations offer a safe option for treating this common dermatological condition. The efficacy of    various treatments varies among individuals, and combination treatment is often useful in patients who do not respond to a single agent.

 

REFERENCES:

(1)     Braun-Falco O, Plewlg G, Wolff HH, Burgdorf WHC:Tupiez zwykty. In: Glinski W, Wolska H, Zaborowski P (ed.): Dermatologia. Czelej, 2000: 440-441.

(2)     Michatowski R: Tupiez pospolity. In: Choroby Wtosow i skory owtosionej. PZWL, Warszawa, 1975: 252-252.

(3)     Adamski Z: Tupiez skory gtowy jako problem dermatologiczny. Mikol. Lek ., 2002, 9(supl.1): 21-24.

(4)     Plewig G, Kligman AM: The effect of selenium sulphide on epidermal turnover of normal and dandruff scalps. J. Soc. Cosmetic chemists, 1969, 20: 767-775.

(5)     Gupta AK, bluhrn R: Seborrheic Dermatits. JEADV 2004, 18: 13-26.

(6)     Hryncewicz-Gwozdz A, Baran E: Flora bakteryjna i grzybicza skory owtosionej gtowy a tupiez gtowy. Mikol. Lek., 2002, 9 (supl.1): 17-20.

(7)     Pierard-Frachimont C, Hemanns JF, Degreef H, pierard GE: From axioms to new insights into dandruff. Dermatology, 2000, 200: 93-98.

(8)     Amdt KA, Hsu JT. Manual of dermatologic therapeutics. 7th ed. Lippicott Williams and Wilkins: Philadelphia PA; 2007.p. 180-4.

(9)     RO BI, Dawson TL. The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and dandruff. J Investig Dermatol Symp Proc 2005;10:194-7.

(10)   Piιrard-Franchimont C, Xhauflaire-Uhoda E, Piιrard GE. Revisiting dandruff. Int J Cosmet Sci 2006;28:311-8.

(11)   Piιrard-Franchimont C, Hermanns JF, Degreef H, Piιrard GE. From axioms to new insights into dandruff. Dermatology 2000;200:93-8.

(12)   Balows A, Sussman M. Medical Mycology, Microbiology and Microbial Infections. Collier, Vol 4, 9th ed., New York: Oxford University Press, Inc.; 1998. p. 201-11.

(13)   Shuster S, Blachford N. Seborrheic dermatitis and dandruff. In: A fungal disease. London: Royal Society of Medical Publishers; 1988. p. 1-30.

(14)   Saint-Leger D, Kligman AM, Stoudemyer TJ. The role of the resident micro flora in the pathogenesis of dandruff. J Soc Cosmet Chem 1988;40:109-17.

(15)   Sanfilippo A, English JC. An overview of medicated shampoos used in dandruff treatment. P and T; 2006. p. 396-400.

(16)   Leyden JJ, McGinley KJ, Kligman AM. Role of microorganisms in dandruff. Arch Dermatol 1976;112:333-8.

(17)   Pierard FC, Arrese JE, Pierard GE. Immunohistochemical aspects of the link between Malassezia ovalis and seborrheic dermatitis. J Eur Acad Dermatol Venereol 1995;4:14-9.

(18)   Gupta AK, Madzia SE, Batra R. Etiology and management of seborrheic dermatitis. Dermatology 2004;208:89-93.

(19)   Jo JH, Jang HS, Ko HC, Kim MB, Oh CK, Kwon YW, et al. Pustular psoriasis and the Kobner phenomenon caused by allergic contact dermatitis from zinc pyrithione-containing shampoo. Contact Dermatitis 2005;52:142-4.

(20)   Pierard GE, Pierard FC. Squamometry in acute photo damage. Skin Res Technol 1995;1:137-9.

(21)   Piιrard-Franchimont C, Xhauflaire-Uhoda E, Piιrard GE. Revisiting dandruff. Int J Cosmet Sci 2006;28:311-8.

(22)   instoresnow.walmart.com/.../01_CHA_10109_0500_SelsunBlue_D_dandruff_US_ENG_01.pdf

(23)   Pierard-Franchimont C, et al. From axioms to new insights into dandruff. Dermatology 2000; 200: 93 Satchell AC, et al. Treatment of dandruff with 5% tea tree oil shampoo. J Am Acad Dermatol 2002; 47: 852

(24)   Elewski BE. Clinical diagnosis of common scalp disorders. J Investig Dermatol Symp Proc 2005;10:190-3.

(25)   Donnarumma G, Paoletti I, Buommino E, Orlando M, Tufano MA, Baroni A. Malassezia furfur induces the expression of β-defensin-2 in human keratinocytes in a protein kinase C dependent manner. Arch Dermatol Res 2004;295:474-81.

(26)   Perkins MA, Cardin CW, Osterhues MA, Robinson MK. A non-invasive tape absorption method for recovery of inflammatory mediators to differentiate normal from compromised scalp conditions. Skin Res Technol 2002;8:187-93.

(27)   Pierard GE, Pierard FC, Oudjin NT, Nikkeis AF, Saint Legar D. Improvement in the inflammatory aspect of androgenic alopecia: A pilot study with an antimicrobial lotion. J Dermatol Treat 1996;7:153-7.

(28)   Warren R, Schwartz JR, Sanders LM, Juneia PS. Attenuation of surfactant induced interleukin 1α expression by zinc pyrithione. Eur J Dermatol 2003;2:23-7.

(29)   Saint-Leger D, Leveque JL. A comparative study of the re-fatting kinetics on the scalp and forehead. Br J Dermatol 1982;106:669-75.

(30)   Piιrard-Franchimont C, Piιrard GE, Kligman A. Seasonal modulation of the sebum excretion. Dermatoligica 1990;181:21-2.

(31)   Catterall MD, Ward ME, Jacobs P. A reappraisal of the role of Pityrosporum versicolor and the significance of extra cellular lipase. J Invest Dermatol 1978;71:398-401.

(32)   Piιrard-Franchimont C, Piιrard GE. Teloptosis: A turning point in hair shedding biorhythms. Dermatology 2001;203:115-7.

(33)   Piιrard-Franchimont C, Petit L, Loussouarn G, Saint-Lιger D, Piιrard GE. The hair eclipse phenomenon, sharpening the focus on the hair cycle chronobiology. Int J Cosmet Sci 2003;25:295-9.

(34)   Piιrard GE, Piιrard-Franchimont C, Marks R, Elsner P; EEMCO group (European Expert Group on Efficacy Measurement of Cosmetics and other Topical Products). EEMCO guidance for the assessment of hair shedding and alopecia. Skin Pharmacol Physiol 2004;17:98-110.

(35)   Shankar SG, Ranjith MS, Ranganathan S, Sivaramakrishnan M, Natarajan V, Rasool SK. Role of ABO blood groups in the infection rate of dandruff caused by Pityrosporum ovale. Ind J Dermatol 2002;47:21-3.

(36)   Balajee SA, Menon T, Ranganathan S. ABO blood groups in relation to the infection rate of dermatophytosis. Mycoses 1996;39:475-8.

(37)   de Angelis Y, MacDonald E, Kramp K, Bacon R, Kaufman DJ, Schwartz R, et al. Broad spectrum antifungal activity of pyrithione zinc and its effect of the cause of dandruff associated itch. Am Acad Dermatol 2004;50:36-8.

(38)   Faergemann J. Atopic dermatitis and fungi. Clin Microbiol Rev 2002;15:545-63.

(39)   Tsuboi R, Sugita T, Tajima M, Amaya M, Tsuboi R, Nishikawa A. Genotype analysis of Malassezia restricta as the major cutaneous flora in patients with atopic dermatitis and healthy subjects. Microbiol Immunol 2004;48:755-9.

(40)   Baden HP, Baden LA. Keratolytic agents. In: Freedberg IM, Eisen AZ, Wolff K, et al., eds. Fitzpatrick’s Dermatology in General Medicine, 6th ed, vol 2. New York: McGraw-Hill; 2003:2352–2355.

(41)   DiSalvo R. 2002 Salicylic acid. The chemistry and manufacture of cosmetics. Volume III . Edited by M.L. Schlossman.

(42)   http://en.wikipedia.org/wiki/Salicylic_acid

(43)   Shapiro J, Maddin S. Medicated shampoos. Clin Dermatol 1996; 14:123–128.

(44)   Bamford JT. Treatment of tinea versicolor with sulfur-salicylic shampoo. J Am Acad Dermatol 1983;8(2):211–213.

(45)   Lin AN, Reimer RJ, Carter DM. Sulfur revisited. J Am Acad Dermatol 1988;18:553–558.

(46)   Gupta AK, Nicol K. The use of sulfur in dermatology. J Drugs Dermatol 2004;3(4):427–431.

(47)   Leyden JJ, McGinley KJ, Mills OH, et al. Effects of sulfur and salicylic acid in a shampoo base in the treatment of dandruff: A double-blind study using corneocyte counts and clinical grading. Cutis 1987;39(6):557–561.

(48)   http://en.wikipedia.org/wiki/Sulfur.

(49)   Marks R, Pearse A. The effects of a shampoo containing zinc pyrithione on the control of dandruff. Br J Dermatol 1985;112: 415–422.

(50)   Gibson W, Hardy W, Groom M. The effect and mode of action of zinc pyrithione on cell growth: II. In vivo studies. Food Chem Toxicol 1985;23(11):103–110.

(51)   Warner RR, Schwartz JR, Boissy Y, Dawson TL. Dandruff has an altered stratum corneum ultrastructure that is improved with zinc pyrithione shampoo. J Am Acad Dermatol 2001;45(6):897–903.

(52)   http://en.wikipedia.org/wiki/Zinc_pyrithione

(53)   Shuster S. The aetiology of dandruff and the mode of action of therapeutic agents. Br J Dermatol 1984;3:235–242.

(54)   Danby FW, Maddin WS, Margesson LJ, Rosenthal D. A randomized, double-blind, placebo-controlled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of moderate to severe dandruff. J Am Acad Dermatol 1993;29(6): 1008–1012.

(55)   Pierard-Franchimont C, Pierard GE. Subjects using antidandruff shampoos. J Eur Acad Dermatol Venereol 1995;5:S153.

(56)   Rapaport M. A randomized, controlled clinical trial of four antidandruff shampoos. J Int Med Res 1981;9(2):152–156.

(57)   Van Cutsem J, Van Gerven F, Fransen J, et al. The in vitro antifungal activity of ketoconazole, zinc pyrithione, and selenium sulphide against Pityrosporum guinea pigs. J Am Acad Dermatol 1990;22:993–998.

(58)   Cauwenbergh G, De Doncker P, Schrooten P, et al. Treatment of dandruff with a 2% ketoconazole scalp gel: A double-blind placebocontrolled study. Int J Dermatol 1986;25:541.

(59)   ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s160sele.pdf

(60)   Robinson JR, Gauger LJ. Dermatitis, dry skin, dandruff, seborrheic dermatitis and psoriasis products. In: Nonprescription Products, Formulations, and Features, 8th ed. Washington, DC: American Pharmaceutical Association; 1986:30:597–623.

(61)   Pierard-Franchimont C, Pierard GE, Vroome V, Lin GC, Appa Y. Comparative anti-dandruff efficacy between a tar and a non-tar shampoo. Dermatology 2000;200(2):181–184.

(62)   Milani M, Antonio Di Molfetta S, Gramazio R, et al. Efficacy of betamethasone valerate 0.1% thermophobic foam in seborrheic dermatitis of the scalp: An open-label, multicentre prospective trial on 180 patients. Curr Med Res Opin 2003;19(4):342–345.

(63)   Pierard-Franchimont C, Goffin V, Decroix J, Pierard GE. A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis. Skin Pharmacol Appl Skin Physiol 2002;15(6):434–441.

(64)   www.wikipedia.com

(65)   Kedor-Hackmann E, Nery MMF and Santoro MI. Determination of ketaconazole in pharmaceutical preparations by ultra violet Spectrophotometry and high performance liquid chromatography. Anal. Lett. 1994; 27: 363-376.

(66)   Squire R, Goode K. A randomized, single-blind, single-center clinical trial to evaluate comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5%) and salicylic acid (3%), or ketoconazole (2%) for the treatment of dandruff/seborrheic dermatitis. J Dermatol Treat 2002;13(2):51–60.

(67)   Angela Sanfilippo, MD, and Joseph C. English III, MD; An Overview Of Medicated Shampoos Used In Dandruff Treatment; 400 P and T® ,July 2006, Vol. 31page No. 7

(68)   www.specchemind.com/images/po.pd

(69)   www.makingcosmetics.com/inci-list/inci-anti-dandruff.htm

 

 

 

 

Received on 10.02.2011                    Accepted on 20.02.2011        

©A&V Publications all right reserved

Res. J. Topical and Cosmetic Sci. 2(1): Jan. –June 2011 page 01-10