Physical Pharmacy-I

PCU-822

SURFACTANTSSurfactants are termed as surface-active agents also wetting agents, emulsifying agents or suspending agents depending on its properties and use.

Surface-active agents are substances which, at low concentrations, adsorb onto the surfaces or interfaces of a system and alter the surface or interfacial free energy and the surface or interfacial tension.

Surfactants are monomers, it has a characteristic structure possessing both hydrophobic groups / non-polar regions (their "tails") usually contain a C12C18 hydrocarbon chain and hydrophilic groups / Polar Regions (their "heads"). Therefore, they are soluble in both organic solvents and water, so they called amphiphilic.

Mechanism of ActionSurfactants can work in three different ways:

1. Roll-up,

2. Emulsification and

3. Solubilization.

Solubilization: Through interaction with the micelles of a surfactant in a solvent (water), a substance spontaneously dissolves to form a stable and clear solution.Classification of surfactants:Surfactant can be classified based on charge groups present in their head. A nonionic surfactant do not have any charge groups over its head. The head of an ionic surfactant carries a net charge. If the charge is negative, the surfactant is more specifically called anionic and if the charge is positive, it is called cationic.If a surfactant contains a head with two oppositely charged groups, it is termed zwitterion.

1. Anionic surfactants2. Cationic surfactants3. Non-ionic surfactants4. Zwitterionic/ amphoteric surfactants1. Anionic surfactants:In solution, the head is negatively charged. These surfactants are the most widely used type of surfactant for preparing shampoos because of its excellent cleaning properties and high hair conditioning effects. Anionic surfactants are particularly effective at oil cleaning and oil/clay suspension.

The most commonly used anionic surfactants are alkyl sulphates, alkyl ethoxylate sulphates and soaps. Most of the anionic surfactants are carboxylate, sulfate and sulfonate ions.The straight chain is a saturated /unsaturated C12-C18 aliphatic group. The water solubility potential of the surfactant is determined by the presence of double bonds.

2. Cationic Surfactants:In solution, the head of the cationic surfactant is positively charged. Cationic surfactants are quaternary ammonium compounds and they are mostly used for their disinfectant and preservative properties as they have good bactericidal properties. They are used on skin for cleansing wounds or burns. Mostly used cationic surfactants are cetrimide which has tetradecyl trimethyl ammonium bromide with minimum amount of dodecyl and hexadecyl compounds Other cationic surfactants are benzalkonium chloride, cetylpyridinium chloride etc.

3. Non-Ionic Surfactants: Those surfactants do not have any electrical charge, which makes them resistant to water hardness deactivation. They are less irritant than other anionic or cationic surfactants. The hydrophilic part contains the polyoxyethylene, polyoxypropylene or polyol derivatives. The hydrophobic part contains saturated or unsaturated fatty acids or fatty alcohols They are excellent grease/oil removers and emulsifiers.

The non ionic surfactant can be classified as

Polyol esters , polyoxyethylene esters , poloxamers The Polyol esters includes glycol and glycerol esters and sorbitan derivatives. Polyoxyethylene esters includes polyethylene glycol (PEG 40, PEG -50 PEG-55). The most commonly used non-ionic surfactants are ethers of fatty Alcohols.4. Amphoteric/Zwitterionic Surfactants: These surfactants are very mild, making them particularly suited for use in personal care preparations over sensitive skins. They can be anionic (negatively charged), cationic (positively charged) or non-ionic (no charge) in solution, depending on the acidity or pH of the water. Those surfactants may contain two charged groups of different sign. Whereas the positive charge is almost always ammonium but the source of the negative charge may vary (carboxylate, sulphate, sulphonate).

These surfactants have excellent dermatological properties. They are frequently used in shampoos and other cosmetic products, and also in hand dishwashing liquids because of their high foaming properties.PROPERTIES OF SURFACTANT1. Wetting of Solids

2. Solubilization

3. Emulsification

4. Dispersion of solid in solution

5. Micellization

6. Detergency

MICELLIZATION Definition- A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. The process of forming micelle is known as micellization. Micelle formations in polar and non-polar solvent depend on the concentration of the surfactant in the particular solvent. If add surfactant (monomers) in solvent, at low concentration some monomers dispersed in solvent or aggregate at the surface or interface until all surface or interface saturated by surfactant. Further addition of surfactant increase concentration of monomers and it goes in solvent and start to form micelles. This concentration is called CMC. [Critical micelle concentration].CMC (critical micelle concentration): The concentration of monomer at which the micelles are start to form in solvent at particular temperature. Micelles form only when the concentration of surfactant is greater than the critical micelle concentration (CMC).

Solubilization Solubilization can be defined as the preparation of a thermodynamically stable isotropic solution of a substance normally insoluble or very slightly soluble in a given solvent by the introduction of an additional amphiphilic component or components. The amphiphilic components (surfactants) must be introduced at a concentration at or above their critical micelle concentrations. Simple micellar systems (and reverse micellar) as well as liquid crystalline phases and vesicles referred to above are all capable of solubilization. In liquid crystalline phases and vesicles, a ternary system is formed on incorporation of the solubilizate and thus these anisotropic systems are not strictly in accordance with the definition given above.Solubilization by micelles The location of a solubilized molecule in a micelle is determined primarily by the chemical structure of the solubilizate.

Solubilization can occur at a number of different sites in a micelle:

Examples1. Polar alcohols are soluble in aqueous solution, so it located in solution / on surface of micelle.

2. Phenol are having polar OH group and non polar benzene ring. In which OH gr. Located in hydrophilic environment and benzene ring in hydrophobic environment, so it located at the surface and between the hydrophilic head groups.

3. Semi polar materials, such as fatty acids are usually located in the palisades layer, the depth of penetration depending on the ratio of polar to non-polar structures in the solubilisate molecule.

4. Non-polar additives such as hydrocarbons tend to be intimately associated with the hydrocarbon core of the micelle.

Pharmaceutical Examples of solubilization1. The solubilization of phenolic compounds such as cresol, chlorocresol, chloroxylenol and thymol with soap to form clear solutions for use in disinfection.

2. Solubilized solutions of iodine in non-ionic surfactant micelles (iodophors) for use in instrument sterilization.

3. Solubilization of drugs (for example, steroids and water insoluble vitamins), and essential oils by non-ionic surfactants (usually polysorbates or polyoxyethylene sorbitan esters of fatty acids).

APPLICATION OF SURFACTANTS IN PHARMACEUTICALSSOLID DOSAGE FORMS Surface-active agents have been widely shown to enhance drug dissolution rates.

This may be due to wetting effects, resulting in increased surface area, effects on solubility and effective diffusion coefficient or a combination of effects.

Consequently surfactants have been included in tablet and capsule formulations to improve wetting and de-aggregation of drug particles and thus increase the surface area of particles available for dissolution.

This wetting effect is found to be operative at concentrations below the CMC.

The effect of surfactants on the dissolution of solids is complex. In addition to effects on the available surface area, surfactants in concentrations above the CMC can increase drug solubility and hence the effective concentration gradient.

However they also reduce the effective rate of drug diffusion as a consequence of drug solubilization within micelles.

I. Hard Gelatin Capsules and TabletsWetting agents: Surfactants are used in capsule and tablet formulations as wetting agents to aid dissolution.

Lubricants, anti-adherents, and glidants. The primary function of tablet lubricants is to reduce the friction arising at the interface of tablet and die walls during compression and ejection.

Lubricants also possess antiadherent (prevention of sticking to the punch and, to a lesser extent, to the die wall) and glidant (improvement of flow characteristics of powders or granulates) characteristics and are useful in the processing of hard gelatin capsules.

Magnesium stearate is used extensively as a lubricant in tablet manufacture. It is an example of a boundary lubricant, that is, the polar regions of the molecule adhere to the metal surface of the die wall (in tablet manufacture).

Adsorption of magnesium stearate to the powder or granule surfaces also prevents agglomeration of the feed material and aids flow.

Lubricants may be classified as water-soluble or water-insoluble. The latter are generally more effective than water-soluble lubricants and can be used at a lower concentration.

Common water-insoluble lubricants (which are surfactants) include magnesium stearate, calcium stearate, sodium stearate, and stearic acid;

water-soluble lubricants include sodium lauryl sulphate and magnesium lauryl sulphate.

Sodium lauryl sulphate is used in the production of hard gelatin capsules where it is added to the gelatin solution during the preparation stage.

The stainless steel molds are lubricated prior to dipping into the gelatin solution and sodium lauryl sulphate is added to reduce the surface tension of the mix and cause the mold pins to wet more uniformly.

II. Suppositories Several non-ionic surface-active materials have been developed as suppositories vehicles.

Many of these bases, known as water-dispersible bases, can be used for the formulation of both water-soluble and oil soluble drugs.

The surfactants most commonly used are the polyoxyethylene sorbitan fatty acid esters (Tweens), the polyoxyethylene stearates, and the sorbitan fatty acid esters (Spans).

Surface-active agents are widely used in combination with other suppository bases.

The inclusion of these agents in the formulation may improve the wetting and water-absorption properties of the suppository. In addition, emulsifying surfactants help to keep insoluble substances suspended in a fatty base suppository.

The inclusion of a surfactant in the suppository formulation may enhance the rectal absorption of drugs.

LIQUID SYSTEMSFormulation of SolutionSurfactants used in Formulation of Solution as solubilizing agent, which increase Drug solubility. It includes Sorbitan mono oleate and PEG. It used in rang 0.05-0.5% to avoid toxicity.[26]

Formulation of Suspension (Dispersants) Surfactants may be used in the formulation of suspension to aid dispersion of the solid particles in the liquid.

This is particularly important if the powder is not readily wetted by the liquid vehicle. Surfactants can reduce the interfacial tension between the solid particles and the liquid vehicle.

The advancing contact angle is reduced, and wetting of the solid particles promoted. Such a system is said to be deflocculated.

The inclusion of a surface-active agent to improve powder wettability can often improve the bioavailability of the formulation.

Surfactants in mouth washes: Mouthwashes are aqueous solutions often in concentrated form containing one or more active ingredients or excipients.

They are used by swirling the liquid in the oral cavity.

Mouthwashes can be used for two purposes. They are therapeutic and cosmetic.

Therapeutic mouth rinses or washes can be formulated In order to reduce plaque, gingivitis, dental caries, and stomatitis.

Cosmetic mouthwashes may be formulated to reduce bad breath through the use of antimicrobial and/or flavouring agents.

Surfactants are used because they aid in the solubilization of flavours and in the removal of debris by providing foaming action.

Surfactants as cerumen removing solutions: Cerumen is a combination of the secretions of sweat and sebaceous glands of the external auditory canal.

The secretions, if allowed to dry, form a sticky semisolid which holds shredded epithelial cells, fallen hair dust and other foreign bodies that make their way into the ear canal. Excessive accumulation of cerumen in the ear may cause itching, pain, impaired hearing and is a deterrent to otologic examination.

Recently, solutions of synthetic surfactants have been developed for their cerumenolytic activity in the removal of ear wax.

One of these agents are tri ethanolamine polypeptide oleate-condensate, commercially formulated in propylene glycol, is used to emulsify the cerumen thereby facilitating its removal (Cerumenex drops).

Another commercial product utilizes carbamide peroxide in glycerin/propylene glycol (Debrox drops). On contact with the cerumen, the carbamide peroxide releases oxygen which disrupts the integrity of the impacted wax, allowing its easy removal.

Brands in Pakistan are:

ABBOWAX drops, CARBOWAX drops

SEMISOLID SYSTEMSSurfactants are major constituents of pharmaceutical, cosmetic, and food semisolid formulations, many of which are emulsions, either oil in water (o/w) or water in oil (w/o). They are included for their stabilizing, wetting, solubilizing, detergent and penetration enhancing properties.

Emulsion formulation: Water-in-oil emulsions traditionally contain surfactants of natural origin such as cholesterol, wool fat, wool alcohols, lanolin, divalent salts of fatty acids soaps, calcium oleate and/or synthetic agents of low hydrophilic-lipophilic balance (HLB) (indicating high lipophilicity), such as Spans (fatty acid esters of sorbitan).

The water soluble surfactant may be anionic (e.g., sodium lauryl sulphate), cationic (e.g., cetrimide), or non-ionic (e.g., cetomacrogol, Tweens).

Mixed emulsifiers control the consistency of a cream by forming a viscoelastic network throughout the continuous phase of the emulsion. The network results from the interaction of the mixed emulsifier with water, forming a liquid crystalline phase.

Formulation of OintmentsOintments are semisolid preparation meant for external application to skin or mucous membrane; they usually contain medicaments or medicaments in dissolved, suspended or emulsified in an ointment base. Sometimes in the ointment preparation surfactants are useful for the easy removal from the skin by washing with water & also for the consistency by reduction of surface tension.

Surfactants are also used in formulation of cold cream, cleansing cream, vanishing cream, shaving cream or any media.

Formulation of ShampooShampoo is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair. The goal is to remove the unwanted build-up without stripping out so much as to make hair unmanageable.

Shampoo, when lathered with water, is a surfactant, which, while cleaning the hair and scalp, can remove the natural oils (sebum) which lubricate the hair shaft.

Formulation of Aerosols Surfactants are found in both solution and suspension formulations of metered dose inhalers (MDIs).

The most common surfactants found in pressurized aerosol preparations include

sorbitan trioleate (Span 85),

oleic acid, and

Lecithin

These agents are non-volatile liquids which dissolve in the propellant blend.

Their function in the formulation is to provide lubrication for the metering valves and, in the case of suspension formulations, to maintain the disperse nature of the drug.

Hydrophobic tail

Hydrophilic head

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