Non-ionic surfactants and their applications

Unit 2 PPD B pharm SEMESTER 8
Surfactants are a type of molecules that contains both water-loving(hydrophilic) and water-fearing (hydrophobic) portions.
Some surfactants possess an electrical charge on their hydrophilic moiety and based on the type of the electrical charge(s) or absence of electrical charge.
Surfactants are categorised as non-ionic (no charge), anionic (negative charge), cationic (positive charge) and amphoteric (containing both a positive and a negative charge).
Many of these compounds provide exceptional properties to a formulation for specific applications such as low-foaming cleansers, rapid-wetting properties, water solubility enhancers and emulsifiers for water insoluble compounds.
Non-ionic surfactants consisting of a hydrophilic head group and a hydrophobic tail, used in the preparation of niosomes, carry no charge and are relatively non-toxic.

1. Non-ionic surfactants Rudrani Pednekar Roll No- 55 Semester- VIII Fourth Year Bpharm

2. Surfactants are a type of molecules that contains both water-loving(hydrophilic) and water-fearing (hydrophobic) portions. Some surfactants possess an electrical charge on their hydrophilic moiety and based on the type of the electrical charge(s) or absence of electrical charge. Surfactants are categorised as non-ionic (no charge), anionic (negative charge), cationic (positive charge) and amphoteric (containing both a positive and a negative charge). Many of these compounds provide exceptional properties to a formulation for specific applications such as low-foaming cleansers, rapid-wetting properties, water solubility enhancers and emulsifiers for water insoluble compounds. Non-ionic surfactants consisting of a hydrophilic head group and a hydrophobic tail, used in the preparation of niosomes , carry no charge and are relatively non-toxic.

3. Non-ionic surfactants are one of the most commonly used surfactant in pharmaceutical industry because of their milder action. Non-ionic surfactants exists both in liquid and slurry form and their aqueous solubility decreases with increase in temperature. These surfactants are commonly used in the cosmetic and personal care products including shampoos (to aid in emulsification), perfumes (as a solubilizing agents), color cosmetics (to help disperse in make-up) and creams (to assist in the emulsification of oils) for skin products. The major applications of non-ionic surfactants are due to their increased spreading, wetting, sticking and penetration abilities.

4. Classification of Non-ionic Surfactants The non-ionic surfactants are classified as: Ethoxylated alcohols and alkylphenols Polyoxyethylated glycol monoethers Fatty acid esters Nitrogenated non-ionic surfactants

5. Ethoxylated alcohols and alkylphenols: Ethoxylated linear alcohols : Alcohols with linear alkyl groups are the best to be used as surfactant. Primary alcohols have their -OH group at the end of the chain. The most used alcohol is tridecanol , a C12-C16 mixture. The ethoxylation (EON) degree ranges from 6-10 for detergents, >10 for soap dispersants, wetting agents and emulsifiers. Foaming ability passes through a maximum for a proper ethoxylation degree, for example dodecanol (EON= 30). Ethoxylation is a chemical reaction in which ethylene oxide adds to a substrate. Ethoxylated alkyl-phenols: Common ethoxylated alkyl-phenol surfactants are the octyl, nonyl and dodecyl-phenol(EON= 4 to 40). Octyl and nonyl-phenols(EON=8 to 12) are used as detergents.

6. With EON <5 the surfactants are antifoaming agents or detergents in non-aqueous media. With EON ranging from 12 to 20, they are wetting agents and o/w emulsifiers. Surfactants with EON >20 exhibit detergents properties at high temperature and high salinity. Ethoxylated thiols: Thiols (the alcohol structure in which the O atom is replaced by S atom) can be ethoxylated just as alcohols or phenols. The corresponding surfactants are excellent detergents and wetting agents. Ter-dodecyl mercaptan (EON= 8 to 10) exhibits a good solubility in both water and organic solvents and is excellent industrial detergents.

7. Polyoxyethylated glycol monoethers : Polyoxyethylated glycol monoethers have the general structure CxEy , where x and y denote the alkyl and ethylene oxide chain length, for example, C12E6 represents hexaoxyethylene glycol monododecyl ether. One of the most widely used compounds is Cetomacrog ol 1000 B.P.C., which is water soluble, with an alkyl chain length of 15 or 17 and an ethylene oxide chain length between 20 and 24. Several other polyoxyethylated monoethers are commercially available, such as Brij series C12E4(Brij 30) to C12E23(Brij 35).

8. Fatty acid esters: The esterification of a fatty acid by a -OH group from polyethylene oxide chain tip or polyalcohols generates non-ionic surfactants that are compatible with biological tissues, which make them suitable for pharmaceutical and cosmetic use. Glycerol esters: Triglycerides which are found in most vegetable and animal oils and fats are triesters of glycerol and are not hydrophilic enough to be water soluble. Glycerol mono- and di-esters, so called mono and diglycerides can exhibit surfactant properties. Glycerol esters and derivatives are used in pharmaceuticals as emulsifiers, dispersants and solubilizing agents. Esters of hexitols and cyclic anhydrohexitols : The most common hexitols is sorbitol obtained by the reduction of D-glucose. Two hydroxyl groups merge to produce an ether link resulting in a 5 or 6 atom cycle called sorbitan .

9. In some cases a two ether link results in bi- anhydrosorbital product called isosorbide. The sorbitan ring exhibits 4 hydroxyl groups wher e as isosorbide bicycle has only 2 hydroxyl groups. Commercial sorbitan esters (Span) and their ethoxylated counterparts (Tween) can have a lipophilic group ranging from monolaurate(one C12) to trioleate(three C18). Tween 20 displays a hydrophilic part, is much bulkier than its lipophilic tail. Although these molecules are very complex they are biologically compatible. The commercial product is always a mixture of many different sub s tances that produce excellent emulsifying agents widely employed in pharmaceuticals and cosmetics. Sorbitan esters (Spans): Sorbitan esters are supplied commercially as Spans and are mixtures of the partial esters of sorbitol and its mono- and di-anhydrides with oleic acid. The sorbitan esters are insoluble in water but soluble in most organic solvents with low HLB value and are used as w/o emulsifiers and wetting agents. Some examples of Span surfactants are Sorbitan monolaurate(Span 20), Sorbitan monopalmitate (Span 40), Sorbitan monostearate(Span 60), etc.

10. Polysorbates(Tweens): Polysorbates are complex mixtures of partial esters of sorbital and its mono- and di-anhydrides condensed with an approximate number of moles of ethylene oxide. They are supplied commercially as Tweens. Examples of Tween surfactants are Polyoxyethylene (20) sorbitan monolaurate(Tween 20), Polyoxyethylene (20) sorbitan monopalmitate (Tween 40) etc. Nitrogenated non-ionic surfactants: Products such as ethoxylated amines consist of fatty amine with one or two polyethylene glycol chains. They are used as emulsifiers with a better water solubility than most cationic surfactants. Ethoxylated alkyl-amides are good foaming agents. Ethoxylated and acylated urea are biocompatible exhibiting favourable effect on the skin tissues and are used as additives in liquid soaps. Tertiary amine oxides are used as foam boosters. Some products includes two amine oxide groups with the amine H often replaced by ethanol groups used in bubble bath, hand dish-washing detergents and baby shampoos.

11. APPLICATIONS OF NON-IONIC SURFACTANTS Non-ionic surfactants are used for the preparation of niosomes . Examples: polyglycerol alkyl ethers, ester-linked surfactants, polyoxyethylene alkyl ethers, Brij, Spans and Tweens. The non-ionic surfactant can improve the therapeutic effect of proteins and peptides by minimizing clearance time from systemic circulation, increase bioavailability and can target and control drug delivery to the site of action. Example: Peptide insulin is formulated for oral delivery in the form of polyoxyethylene alkyl ether niosomes and can be delivered as a sustained release in the intestine. Non-ionic surfactants are included in the formulations to solubilize the lipophilic drugs and hence are expected to act as enhancers by solubilizing stratum corneum lipids. Example: Tweens enhances the permeation of lidocaine through the skin in the presence of various concentration of propylene glycol. Non-ionic biological surfactants are used as co-emulsifiers for the preparation of the emulsions composed of castor oil, DC- cholestrol or dioleoyl phosphatidylethanolamine. Example: Tween Span, Brij, etc

12. Non-ionic biological surfactants are used in artificial implants, gene transfection, biomembrane , ophthalmology and pharmaceuticals. Inutec SP1, a polymeric-based surfactant system is a graft copolymer based on a naturally occurring polysaccharide namely inulin exhibit superior dissolution behaviour of the drugs upon solid dispersion due to its surface-active nature They can be used to enhance dissolution properties of drugs such as spherical agglomerate crystals of felodipine. For example: Inutec SP1. The non-ionic low ethoxylated monoglyceride can be used as a skin conditioner, for example, PEG-7 glyceryl cocoate . They are used to prepare o/w emulsions and also as a solubilizing agent for volatile oils, Example: Cetomacrog o l emulsifying wax.

13. REFERENCE: Pharmaceutical Product Development- NIRALI PRAKASHAN (Page no- 2.19) A text book of Pharmaceutical Product Development-Pee Vee (Ashok Koshta )- Page no- 185

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