Liquid Dosage FormPharmaceutical PreparationDrugSuspendedDissolvedDispersedLiquid vehicle (alcohol, water, oil, etc.)It is ready to use and easy to administer.It is easy to swallow and acts faster.It is suitable for children, elderly, and seriously illpatients.It can be given by oral, topical, or parenteral routes.Advantage of Liquid Dosage FormMono PhasicBi Phasic Liquid Dosage FormFor internal useFor external useFor internal useSyrupsElixirsLinctusesOral dropsMouthwashesGarglesLotionsLinimentsPaintsEye dropsEar dropsNasal dropsOral suspensionsOral emulsionsTopical suspensionsTopical emulsionsFor external useOphthalmic suspensionsOtic suspensionsNasal suspensionsMono PhasicMonophasic liquid dosage forms are uniform liquidpreparations.The drug is completely dissolved in a suitable solvent.They form a single-phase system.The drug is evenly distributed at the molecular level.Shaking is not required before use.They provide accurate dosing and good stability.Examples include solutions, syrups, elixirs, tinctures,mouthwashes, eye drops, nasal drops, and injections.They are widely used due to easy administration and rapidabsorption.Bi PhasicColloidSolutionSingle PhaseBiphasic liquid dosage forms are non-uniform(heterogeneous) liquid preparations.They consist of two distinct phases.The drug is present as solid particles or as one liquiddispersed in another.Shaking is required before use for proper drug distribution.There are two main types of biphasic liquid dosage forms.Suspensions contain insoluble solid drug particlesdispersed in a liquid.Emulsions contain one liquid (oil or water) dispersed inanother immiscible liquid.Emulsions require an emulsifying agent for stability.They are used when drugs cannot be prepared as true solutions.Different PhaseEmulsions Suspensions Syrupsconcentrated, viscous, aqueous liquid preparationcontaining one or more dissolved drugs in a highconcentration of sugarTypes of syrups(about 60–85% w/v)Simple syrupMedicated syrupFlavored syrupNon-sucrose syrupSugar + Purified waterSugar + Purified water + APISugar + Purified water + API + flavoring agentsSugar Alternative + Purified water66.7% w/w sucrose60–85% w/v sucrosesugar substitutes such as sorbitol or glycerin60–85% w/v sucrose with added flavoring agentsMethods of preparation of syrupsFormulations of Pharmaceutical SyrupsSimple Syrup IPIngredientsSucrose 66.7% w/vPurified Water q.s.Method usedSolution with the aid of heatParacetamol SyrupIngredientsParacetamol 120 mgSucrose 60–65% w/vGlycerin 5 mlSodium benzoate 0.1%Flavour and colour q.s.Purified water q.s. to 5 mlMethod usedSolution by agitation without heat(Paracetamol is dissolved in a suitable solvent and addedto syrup base prepared separately)solidliquidliquidliquidcan't mixsuspensionemulsionElixirElixirs are clear, transparent, aromatic, sweetenedhydroalcoholic liquid preparations intended for oral use.They contain both alcohol and water as solvents.Alcohol content usually ranges from 4% to 40% (ethanol).They provide a palatable means of administering potentor nauseous drugs.Elixirs are less sweet and less viscous than syrups andmay contain little or no sucrose.They are more stable than syrups and therefore oftenpreferred over syrups.Alcohol acts as both a solvent and a preservative, soadditional preservatives are generally not required.Glycerin and syrup may be added to increase solubility ofmedicaments or for sweetening purposes.Suitable flavoring and coloring agents may be included toimprove palatability and appearance.They are mainly used for drugs that are soluble in alcoholor hydroalcoholic mixtures.Types of ElixirsNon-medicated elixirsMedicated elixirsnot contain any medicamentMedicated elixirsAromatic elixirantibiotics, antihistamines, or sedativesMethod of Preparation of ElixirsElixirs are prepared by simple dissolution withagitation or by mixing two or more liquids.All ingredients are dissolved in their respectivesolvents; alcohol-soluble ingredients aredissolved in alcohol, and water-solubleingredients are dissolved in water.The required alcoholic strength is maintainedby adding the aqueous solution slowly to thealcoholic solution.The mixture is then made up to the requiredvolume (q.s.).At this stage, the preparation may appearcloudy due to separation of some flavoringagents as the alcoholic strength is reduced.The elixir is allowed to stand for some time,during which oil globules precipitate.Talc may be added to absorb excess oils.Finally, the preparation is filtered to obtain aclear elixir.LinimentLiniments are liquid or semi-liquid preparations meant forapplication to the skin.They are usually applied with friction and rubbing onthe affected area.Liniments may be alcoholic solutions, oily solutions, oremulsions.In alcoholic liniments, alcohol helps in penetration ofthe medicament into the skin and enhances counter-irritant and rubefacient action.In oily liniments, arachis oil is commonly used as itspreads easily over the skin.Some liniments contain soap, which aids in easyapplication and spreading on the skin.Liniments should not be applied on broken or injuredskin as they may cause excessive irritation.They usually contain medicaments with analgesic,rubefacient, or counter-irritant properties.Commonly used for relief of joint pain, muscle pain, andsimilar conditions.Simple dissolution with agitation (or mixing oftwo or more liquids)Dissolve ingredients separately • Alcohol-soluble ingredients → Alcohol • Water-soluble ingredients → Purified waterSlowly add aqueous solution to alcoholic solution(Continuous stirring to maintain requiredalcoholic strength)Make up to required volume (q.s.)Allow to stand (Oil globulesprecipitate)Add talc (if required) (Toadsorb excess oils)Pack in well-closed containersFilter the preparationClear Elixir ObtainedSelect suitable base(Oily base or alcoholic / hydroalcoholic base)Dissolve or disperse medicaments(Counter-irritants, analgesics, rubefacients)Prepare separate solution if required(Alcohol-soluble ingredients → AlcoholOil-soluble ingredients → Oil)Combine all components(With continuous stirring to obtain uniform mixture)Add excipientsMake up to required volume (q.s.)Uniform Liniment ObtainedCheck uniformity andappearance Filter if necessary• Emulsifying agent (if required)• Preservative (if required)• Perfume or fragranceLabel: “For external use only – Not to be applied on broken skin”Pack in suitable, well-closed containersMethod of Preparation of LinimentMethod of Preparation of ElixirsGeneral Formula ElixirsActive medicament – Therapeutic agentAlcohol (4–40%) – Solvent and preservativePurified water – VehicleSweetening agent (sucrose, sorbitol, glycerin) – Improves palatabilityFlavoring agent – Enhances tasteColoring agent – Improves appearance (if required)Preservative – Prevents microbial growth (if required)Purified water / Alcohol – To make up the final volumeGeneral Formula Liniment Active medicament – Therapeutic agentOil base (sesame oil, mustard oil, arachis oil) or Alcoholic base – VehicleCounter-irritant (menthol, camphor, methyl salicylate) – Relieves painEmulsifying agent – If emulsion type linimentPreservative – If requiredPerfume / Flavoring agent – Improves odorBase – q.s. to make final volumeLotionsLotions are liquid or semi-liquid preparations intended forexternal application to the skin without rubbing.They are generally applied by pouring, dabbing, orspreading gently on the affected area.Lotions may be solutions, suspensions, or emulsions.They are usually aqueous or hydroalcoholic in nature.Lotions are used for soothing, protective, cooling,antiseptic, or antipruritic purposes.They are suitable for application on inflamed, irritated,or broken skin, depending on the formulation.Lotions contain medicaments such as antiseptics,astringents, antipruritics, or emollients.Shaking is required before use when the lotion is in suspension form.They are commonly used in conditions like skininfections, itching, sunburn, and inflammation.Select suitable base(Aqueous base, hydroalcoholic base, oremulsion base)Dissolve or disperse medicaments(Counter-irritants, analgesics, rubefacients)Prepare separate solution if required(Water-soluble ingredients → Purified waterOil-soluble ingredients → Oil phase)Add excipientsMake up to required volume (q.s.)Uniform Lotion ObtainedCheck uniformity andappearance Filter if necessary• Emulsifying agent (if required)• Preservative (if required)• Perfume or fragrancePack in suitable, well-closed containersCombine phases(With continuous stirring to ensure uniformity)• Stabilizer (if required)Label: “For external use only”Method of Preparation of LotionsMouthwashesMouthwashes are aqueous or hydroalcoholic liquidpreparations intended for use in the oral cavity.They are used to cleanse, deodorize, and disinfect themouth and throat.Mouthwashes are not meant to be swallowed and shouldbe spat out after use.They may contain antiseptics, deodorants, astringents,analgesics, or fluoride.Alcohol, when present, acts as a solvent, preservative, andenhances antibacterial action.Sweetening and flavoring agents are added to improvepalatability.Coloring agents may be included for appearance.Mouthwashes help in maintaining oral hygiene andpreventing dental caries, gum diseases, and bad breath.GarglesGargles are liquid preparations intended for localapplication to the throat.They are used by holding the solution in the mouth andthroat and gargling without swallowing.Gargles may be aqueous, hydroalcoholic, or containantiseptic solutions.They often contain medicaments with antiseptic,astringent, or analgesic properties.Flavoring agents are added to improve taste andacceptability.Gargles are used in conditions such as sore throat,pharyngitis, tonsillitis, and oral infections.They help to reduce microbial load, soothe irritation, andprovide symptomatic relief.Throat PaintThroat paints are viscous liquid or semi-liquid preparations intendedfor local application to the throat.They are applied directly to the affected area using a brush orswab.The medicaments in throat paints usually have antiseptic,astringent, or anesthetic properties.Throat paints provide a protective coating and relieveirritation, inflammation, or pain.They are particularly useful in treating conditions likepharyngitis, tonsillitis, and mouth ulcers.The formulation is designed to adhere to the mucousmembrane and remain in contact for a prolonged effect.Flavoring agents may be added to improve patientcompliance.Ear Drops (Otic Drops)Ear drops are liquid preparations intended for local application into theear.They may be solutions, suspensions, or emulsions.Ear drops contain medicaments with analgesic, antiseptic, anti-inflammatory, or cerumenolytic properties.The drops are used to treat ear infections, relieve pain, remove wax, orreduce inflammation.Some ear drops may include oils (like olive oil) to soften earwax.Proper administration involves tilting the head to allow the drops toreach the ear canal.They are designed for external use only and should not be swallowed.Flavoring is generally not required since they are not ingested.EnemasEnemas are liquid preparations intended to be introduced into therectum.They are used for local or systemic therapeutic effects.Enemas may be aqueous or oily solutions or suspensions.They are commonly used to relieve constipation, cleanse the bowelbefore surgery or diagnostic procedures, and administer medicaments.Depending on purpose, enemas may act as evacuant, retention, nutritive,or medicated enemas.The volume and composition depend on the intended action.Enemas should be administered gently to avoid irritation or injury tothe rectal mucosa.They are for rectal use only and not for oral administration.Nasal DropsNasal drops are liquid preparations intended for instillation into thenasal cavity.They are usually aqueous or oily solutions.Nasal drops contain medicaments such as decongestants, antiseptics,or antihistamines.They are used to relieve nasal congestion, infections, and allergicconditions.The formulation should be isotonic and non-irritant to the nasalmucosa.Preservatives may be added to prevent microbial growth.Proper administration helps the drug reach the nasal mucosaeffectively.They are meant for local action and should not be swallowed.EmulsionsAn emulsion is a liquid preparation containing two immiscible liquids, one ofwhich is dispersed as fine globules in the other.The dispersed liquid is called the internal (dispersed) phase, while the liquidin which it is dispersed is the external (continuous) phase.The size of dispersed droplets usually ranges from 0.1 to 100 µm in diameter.Emulsions are thermodynamically unstable systems and therefore require anemulsifying agent (emulgent/emulsifier) for stability.Emulsions are no longer official in the Indian Pharmacopoeia (I.P.).They protect drugs that are susceptible to hydrolysis and oxidation.Emulsions can provide a prolonged therapeutic action of the medicament.In the form of an oil-in-water (o/w) emulsion, ephedrine shows a moreprolonged effect when applied to the nasal mucosa compared to its oilysolution.Types of EmulsionOilWater ContinuousPhaseO/WWOW/OWW/O/WO/W/OWOOOWPrimary EmulsionSecondary / Multi-Phasic EmulsionTests For EmulsionsTest NamePrincipleProcedure / ObservationInferenceExampleDilution TestAn emulsion canbe diluted onlywith itscontinuous phaseEmulsion diluted withwater → mixes uniformlyOil-in-Water(O/W)emulsionMilk,VanishingcreamEmulsion diluted withwater → separation orcrackingWater-in-Oil(W/O) emulsionCold cream,ButterDye SolubilityTestDye dissolvesin thecontinuousphaseWater-soluble dye(methylene blue) givesuniform colorO/W emulsionOral emulsionsWater-soluble dyecolors dropletsonlyW/O emulsionTopical creamsOil-soluble dye(Sudan III) givesuniform colorW/O emulsionCold creamConductivityTestWater conductselectricity, oil doesnotShows electricalconductivityO/W emulsionInjectableemulsionsNo or very lowconductivityW/O emulsionOily skincreamsCobalt ChlorideTestCobalt chlorideturns pink inpresence of waterPaper turns pinkO/W emulsionMilkPaper remains blueW/O emulsionButterDilution TestDye Solubility TestConductivity TestTests For EmulsionsDilution TestDye Solubility TestConductivity TestCobalt Chloride TestCobalt Chloride TestCobaltChloride PaperPaper turns pinkPaper remains blueO/W emulsionW/O emulsion• Immiscible – Liquids that cannot mix uniformly with each other, such as oil and water• Cohesive forces – Attractive forces between molecules of the same substance• Adhesive forces – Attractive forces between molecules of different substances• Interfacial tension – The force or energy present at the boundary between twoimmiscible phases due to imbalance of molecular forces• Coalescence – The process by which small droplets merge together to form largerdroplets• Emulsifying agent – A substance that helps stabilize an emulsion by reducinginterfacial tension or forming a protective film• Amphiphilic – Having both water-loving (hydrophilic) and oil-loving (lipophilic) partsin the same molecule• Hydrophilic – Having affinity for water• Hydrophobic – Having repulsion for water or affinity for oil• Lipophilic – Having affinity for fats or oils• Monomolecular film – A single-molecule-thick layer formed at the oil–water interface• Monolayer – A layer that is one molecule thick• Electrostatic repulsion – Repelling force between particles carrying similar electricalcharges• Bancroft rule – A principle stating that the phase in which the emulsifier is moresoluble becomes the continuous phase• Hydrophilic–Lipophilic Balance (HLB) – A numerical scale that indicates the affinityof a surfactant for water or oil• Multimolecular film – A thick film composed of several molecular layers surroundingdroplets• Hydrophilic colloids – High-molecular-weight substances that stabilize emulsionsmainly by forming protective films• Thermodynamic – Related to energy changes and equilibrium in a system• Viscosity – Resistance of a liquid to flow• Adsorption – Accumulation of molecules or particles at an interface or surface• Particulate film – A rigid protective layer formed by solid particles around droplets• Brownian flocculation – Droplet aggregation caused by random thermal motion• Sedimentation flocculation – Droplet aggregation due to gravity-induced settling• Disproportionation (Ostwald ripening) – Growth of larger droplets at the expenseof smaller ones due to diffusion driven by pressure differences• Laplace equation – An equation explaining the relationship between internalpressure and droplet size• Creaming – Separation process where droplets move upward or downward due todensity differences• Precursor – An event or condition that occurs before and leads to another process• Flocculation – Formation of loose clusters of droplets without merging• Breaking (Cracking) – Complete and irreversible separation of emulsion phases• Phase inversion – Conversion of O/W emulsion to W/O emulsion or vice versa• Electrolytes – Substances that dissociate into ions when dissolved in water• Amphoteric substances – Compounds that can act as either acids or bases dependingon pHCohesive forcesAdhesive forcesAdhesive forcesCohesive forcesForceMolecular ForcesInterfacial tensionhydrophiliclipophilicAmphiphilicAdsorptionAbsorption0369121815hydrophobic(oil soluble)hydrophilic(water soluble)Water DispersibleKey exam points to remember:• Higher HLB value → more hydrophilic• Lower HLB value → more lipophilic• O/W emulsions generally require HLB > 10• W/O emulsions generally require HLB < 6TermsTheory of EmulsionsHow Emulsifier Agent Work/How we Stable the EmulsionWhen two immiscible liquids such as oil and water are mixed, they tendto separate because the cohesive forces between molecules of the sameliquid are stronger than the adhesive forces between molecules ofdifferent liquids. This imbalance results in the formation of interfacialtension at the boundary between the two phases. Interfacial tensionrepresents excess free energy at the interface and drives the systemtoward separation.To overcome this natural tendency toward separation and to preventcoalescence of droplets, emulsifying agents are added. These agentsreduce interfacial tension and/or form protective films around disperseddroplets, thereby stabilizing the emulsion.Based on the nature and mechanism of action of emulsifying agents, thetheories of emulsification are broadly classified into:• Monomolecular adsorption theory• Multimolecular adsorption theory• Solid particle adsorption theorycohesive forces > adhesive forcescohesive forces < adhesive forcesEmulsionEmulsionMonomolecular Adsorption Theory (Surfactant Theory)Surface active agents (surfactants) are the most widely used emulsifying agents. A surfactant molecule is amphiphilic, meaning it contains two distinct parts:• A hydrophilic (water-loving) group• A hydrophobic or lipophilic (oil-loving) groupWhen a surfactant is added to a system containing oil and water, the molecules orient themselves at the oil–water interface. The hydrophobic portion dissolves in the oil phase, while the hydrophilic portion remains in the aqueous phase. Thisarrangement leads to the formation of a monomolecular film around the dispersed droplets.Surfactant MoleculeFunctions of surfactants in emulsion stabilization:• They significantly reduce interfacial tension, making it easier to break one liquid into fine droplets within the other.• They form a continuous and coherent monolayer around droplets, acting as a mechanical barrier that prevents droplets from merging when they collide.• Many surfactants impart an electrical charge to the droplet surface, resulting in electrostatic repulsion between adjacent droplets, further reducing the chances of coalescence.Examples:• Tweens (polysorbates)• Spans (sorbitan esters)Hydrophilic head → in waterHydrophobic / Lipophilic tail → in oilHydrophilic → loves waterHydrophobic → hates waterLipophilic → loves oil/fatLipophobic → hates oil/fatHydrophilic ≈ Lipophobic Both prefer waterHydrophobic ≈ Lipophilic Both prefer oilBancroft RuleThe Bancroft rule states that the type of emulsion formed depends primarily on the solubility of the emulsifying agent, rather than on the relative amounts of oil and water. The phase in whichthe emulsifier is more soluble becomes the continuous phase.For example, even if a formulation contains 60% oil and 40% water, it will still form an oil-in-water (O/W) emulsion if the emulsifier used is more soluble in water.This concept is closely related to the Hydrophilic–Lipophilic Balance (HLB) system.• High HLB surfactants (more hydrophilic) favor oil-in-water (O/W) emulsions.• Low HLB surfactants (more lipophilic) favor water-in-oil (W/O) emulsions.Multimolecular Adsorption Theory (Hydrophilic Colloid Theory)Hydrophilic colloids act as emulsifying agents by forming a multimolecular film around the dispersed droplets. Unlike surfactants, these substances have little effect on interfacial tension. Theirstabilizing action is mainly mechanical rather than thermodynamic.At the oil–water interface, hydrophilic colloids adsorb in several molecular layers, producing a thick, strong, and flexible film around the droplets. This film prevents droplets from coming closeenough to coalesce.In addition to film formation, hydrophilic colloids also:• Increase the viscosity of the continuous phase• Reduce the mobility of droplets• Decrease the frequency of droplet collisions• Polysaccharides• Amphoteric substances• Synthetic and semi-synthetic polymersExamples:Acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, tragacanth, gelatin, carbomer resins, cellulose ethers, carboxymethyl chitin, polyethylene oxide polymersTypes of hydrophilic colloidsHydrophilic colloidsSolid Particle Adsorption TheoryAccording to this theory, finely divided solid particles can stabilize emulsions by adsorbing at the oil–water interface. These particles are not soluble in either phase but are wetted by both oiland water.When present in sufficient concentration, the particles form a particulate film around the dispersed droplets. This rigid layer acts as a physical barrier that prevents droplets from coming intodirect contact, thereby inhibiting coalescence.Commonly used finely divided solids:Bentonite, hectorite, kaolin, magnesium aluminium silicate, montmorillonite, aluminium hydroxide, magnesiumhydroxide, silicaSolidEmulsion StabilityEmulsion stability refers to the ability of an emulsion to resist changes in its physical properties over time. Complete breakdown of an emulsion occurs due to several droplet loss mechanisms,including:• Brownian flocculation• Creaming• Sedimentation flocculation• Disproportionation (Ostwald ripening)CreamingCreaming is one of the most common forms of emulsion instability. It involves the upward or downward movement of dispersed droplets under the influence of gravity, depending on densitydifferences.A classic example is milk, where fat globules rise to the top to form cream. Creaming does not represent complete breaking of an emulsion. Instead, it results in separation into twoemulsions:• One layer richer in dispersed phase (cream)• Another layer poorer in dispersed phaseCreaming is usually a precursor to coalescence.The rate of creaming or sedimentation can be estimated using Stokes’ law:υ = 2r²(ρ − ρ₀)g / 9ηwhere:υ = creaming or settling rater = droplet radiusρ = density of dispersed phaseρ₀ = density of continuous phaseη = viscosity of continuous phaseg = acceleration due to gravityReducing droplet size and increasing viscosity decreases the creaming rate.FlocculationFlocculation is the aggregation of droplets into loose, three-dimensional clusters without actual fusion of droplets. Each droplet retains its individual identity.It occurs due to weak attractive forces between droplets and can arise from:• Brownian motion of droplets• Sedimentation-induced collisionsFlocculation increases the effective droplet size and often accelerates creaming, although it does not immediately cause breaking.Disproportionation (Ostwald Ripening)Disproportionation involves the diffusion of dispersed phase molecules from smaller droplets to larger droplets through the continuous phase.Smaller droplets have higher internal pressure than larger ones, as explained by the Laplace equation. This pressure difference causes molecules to diffuse from smaller droplets, which graduallyshrink, to larger droplets, which grow in size. Over time, this leads to instability.CoalescenceCoalescence occurs when two or more droplets fuse to form a larger droplet. During this process, the emulsifier film surrounding the droplets is partially or completely destroyed.Continued coalescence ultimately leads to visible phase separation.Breaking (Cracking)Breaking is the complete and irreversible separation of the oil and water phases. Once breaking occurs, the original emulsion cannot be restored by simple shaking.Phase InversionPhase inversion is a type of physical instability in which an oil-in-water emulsion converts into a water-in-oil emulsion, or vice versa.Phase inversion may be caused by:• Addition of electrolytes• Change in phase volume ratio• Temperature variations• Change in the chemical nature of the emulsifierPhase inversion can be minimized by:• Selecting a suitable emulsifying agent• Using it in adequate concentration• Storing emulsions at appropriate, cool temperaturesBrownian Flocculation Brownian flocculation is a type of reversible physical instability observed in emulsions, especially those with very small droplet sizes. It occurs due to the random thermal motion (Brownianmotion) of dispersed phase droplets within the continuous phase.Concept of Brownian MotionBrownian motion refers to the continuous, random, zig-zag movement of very small particles suspended in a fluid. This motion results from constant collisions between the dispersed dropletsand the molecules of the continuous phase.In emulsions where droplet size is very small (generally less than 1 µm), gravitational forces become negligible and Brownian motion becomes the dominant force governing droplet movement.Mechanism of Brownian FlocculationBecause of Brownian motion, emulsion droplets continuously move and frequently collide with one another. When two droplets come close together:• If the repulsive forces between droplets (electrostatic or steric repulsion) are strong, the droplets separate after collision.• If the attractive forces (van der Waals forces) slightly exceed the repulsive forces, droplets stick together loosely without merging.This loose and reversible aggregation of droplets is known as Brownian flocculation.Factors Affecting Brownian Flocculation• Droplet sizeSmaller droplets exhibit stronger Brownian motion, increasing collision frequency and probability of flocculation.• Interparticle forcesBalance between attractive van der Waals forces and repulsive electrostatic or steric forces determines flocculation.• Electrolyte concentrationAddition of electrolytes compresses the electrical double layer, reduces repulsion, and promotes flocculation.• Nature and concentration of emulsifierInsufficient emulsifier or weak protective films favor flocculation.• Viscosity of continuous phaseHigher viscosity reduces droplet movement and decreases flocculation rate.Sedimentation Flocculation Sedimentation flocculation is a type of physical instability in emulsions that occurs when dispersed phase droplets move under the influence of gravity and aggregate during their downwardmotion. This phenomenon is mainly observed when the dispersed phase is denser than the continuous phase, causing droplets to settle at the bottom of the container.ConceptIn an emulsion, droplets are constantly subjected to different forces. When the density of the dispersed phase is greater than that of the continuous phase, gravitational force becomesdominant. As a result, droplets tend to settle downward (sedimentation).During this settling process, droplets come into close contact with one another. If the attractive forces between droplets slightly exceed the repulsive forces provided by the emulsifier,the droplets aggregate to form loose clusters. This aggregation without fusion is called sedimentation flocculation.Mechanism of Sedimentation Flocculation• Droplets of the dispersed phase move downward due to gravity.• As droplets settle, their paths intersect, increasing the frequency of collisions.• On collision, droplets may loosely adhere due to van der Waals attraction.• The emulsifier film remains intact, so droplets do not merge.• Flocs formed are larger but still composed of individual droplets.This process is reversible in early stages and the flocs can be redispersed by gentle agitation.Factors Affecting Sedimentation Flocculation• Density difference between phasesGreater density difference increases sedimentation rate and collision frequency.• Droplet sizeLarger droplets settle faster, promoting aggregation.• Viscosity of continuous phaseHigher viscosity slows settling and reduces flocculation.• Nature and concentration of emulsifierWeak or insufficient emulsifier films favor flocculation.• Presence of electrolytesElectrolytes reduce electrostatic repulsion and promote aggregation.Flocculation:In flocculation, particles form loose aggregates called flocs due to weak inter-particle attraction. These flocs settle rapidly, producing a clear supernatant and a loose, fluffy sediment whichis easily redispersed on shaking. Flocculation prevents caking and is therefore preferred for pharmaceutical suspensions.Deflocculation:In deflocculation, particles remain discrete and do not form aggregates due to strong repulsive forces. Sedimentation occurs slowly, resulting in a turbid supernatant and a dense, compactsediment that forms a hard cake. Deflocculated systems are difficult to redisperse and are not preferred in pharmaceutical suspensions.Methods of Preparation of EmulsionsEmulsions are prepared by dispersing one immiscible liquid into another in the presence of a suitable emulsifying agent. The objective of all preparation methods is to reduce droplet size,distribute droplets uniformly, and allow the emulsifier to form a stable protective film around the dispersed phase.• Dry gum method (Continental method)• Wet gum method (English method)• Bottle method• Beaker method• In-situ soap method (Nascent soap method)• Mechanical method• Ultrasonic emulsification method16Dry Gum Method (Continental Method)The Dry Gum Method, also known as the Continental Method, is one of the oldest and most commonly used techniques for preparing emulsions, especially oil-in-water (O/W)emulsions. This method is primarily employed when natural emulsifying agents such as acacia (gum arabic) are used. It is widely applied in pharmaceutical compounding because of itssimplicity and effectiveness when performed correctly.PrincipleThe principle of the Dry Gum Method is based on the ability of natural gums to act as emulsifying agents by reducing interfacial tension between oil and water. In this method, theemulsifying agent is first mixed thoroughly with the oil phase in the absence of water. When water is added, the gum rapidly hydrates and swells at the oil–water interface, forming a thin,protective film around the oil globules. This film prevents the oil droplets from coalescing, resulting in the formation of a stable oil-in-water emulsion. Rapid and continuous trituration isessential to ensure uniform dispersion of oil droplets and proper formation of the primary emulsion.ProcedureAdvantagesThe Dry Gum Method is simple and quick, making it suitable for routine compounding in pharmacies. It does not require complex equipment and can be easily performed using basic laboratorytools. When carried out correctly, it produces fairly stable emulsions using natural gums. This method is especially useful for fixed oils and is widely accepted in pharmaceutical practice.DisadvantagesThis method is not suitable for volatile oils because the vigorous trituration required can lead to evaporation and loss of the oil. It also demands a certain level of skill and experience, asimproper trituration or incorrect order of mixing can result in poor emulsification or unstable products. Additionally, the method is limited mainly to oil-in-water emulsions and may not beeffective for all types of oils or emulsifying agents.• Ingredients are taken in a fixed proportion, usually oil, water, and gum in the ratio of 4 : 2 : 1.• A clean and completely dry mortar is selected, as moisture can interfere with proper emulsification.• The accurately weighed or measured quantity of gum is placed in the mortar.• The oil is added to the gum and triturated thoroughly using a pestle until a smooth, uniform paste is formed. This ensures even distribution of the gum in the oil phase.• The calculated quantity of water is then added all at once to the oil–gum mixture.• Immediate, rapid, and continuous trituration is carried out to allow proper hydration of the gum.• A primary emulsion is formed, indicated by a thick, creamy, white appearance, cracking or snapping sound, and a noticeable increase in viscosity.• After formation of the primary emulsion, additional ingredients such as sweeteners, preservatives, flavoring agents, or coloring agents are added slowly with gentle mixing.• The final emulsion is transferred to a suitable container and made up to the required volume, if necessary.Wet Gum Method (English Method)The Wet Gum Method, also known as the English Method, is a traditional technique used mainly for the preparation of oil-in-water (O/W) emulsions. It is closely related to the Dry GumMethod, with the main difference being the order in which the emulsifying agent, water, and oil are mixed. This method is particularly useful when better control over emulsification is required.PrincipleThe principle of the Wet Gum Method is based on the initial hydration of the emulsifying agent. In this method, the gum is first dispersed in water to form a mucilage. This allows theemulsifying agent to hydrate and swell completely before the oil phase is introduced. When oil is added gradually, the hydrated gum readily adsorbs at the oil–water interface, forming aprotective film around the oil droplets. This film reduces interfacial tension and prevents coalescence of the oil globules, resulting in a stable oil-in-water emulsion.Procedure• A clean mortar is taken and the required quantity of gum is placed in it.• The calculated amount of water is added to the gum and triturated thoroughly until a smooth, uniform mucilage is formed.• This step ensures complete hydration of the gum and prevents the presence of dry gum particles in the preparation.• After preparation of the mucilage, the oil is added slowly in small portions with continuous and steady trituration.• Each portion of oil is completely emulsified before adding the next portion.• Gradual addition of oil allows uniform dispersion of oil droplets throughout the aqueous phase.• Trituration is continued until a creamy, uniform primary emulsion is obtained.• Once the primary emulsion is formed, other ingredients such as preservatives, sweetening agents, flavoring agents, or coloring agents are added with gentle mixing.• The final emulsion is transferred to a suitable container and adjusted to the required final volume.AdvantagesThe Wet Gum Method provides better control over the emulsification process because the emulsifying agent is fully hydrated before oil addition. This reduces the risk of lump formation anduneven dispersion of the gum. It is particularly useful for beginners, as the chances of failure during emulsification are lower compared to the Dry Gum Method.DisadvantagesThis method is more time-consuming than the Dry Gum Method due to the additional step of preparing the mucilage and the slow, gradual addition of oil. The emulsions produced may alsohave slightly larger oil droplet size compared to those prepared by the Dry Gum Method, which can marginally affect the overall stability and appearance of the emulsion.Bottle Method (For Volatile and Low-Viscosity Oils)The Bottle Method is a simple and practical emulsification technique used mainly for preparing oil-in-water (O/W) emulsions containing volatile oils or low-viscosity oils. This method is preferredwhen the use of a mortar and pestle is inconvenient or when there is a risk of loss of volatile components during trituration. It is commonly applied in extemporaneous pharmaceuticalpreparations.PrincipleThe principle of the Bottle Method is based on mechanical dispersion produced by vigorous shaking. In this method, emulsification occurs due to intense agitation in a tightly closedcontainer, which breaks the oil phase into fine droplets. The emulsifying agent, usually a natural gum such as acacia, adsorbs at the oil–water interface during shaking and forms a protectivefilm around the dispersed oil droplets. This film reduces interfacial tension and prevents the oil droplets from coalescing, resulting in the formation of an emulsion.Procedure• A clean, dry bottle of sufficient capacity is selected to allow effective shaking.• The accurately measured quantity of gum is placed into the bottle.• The required amount of oil is added to the gum.• The bottle is tightly closed and shaken vigorously until the gum is uniformly dispersed in the oil.• Water is then added in small portions.• After each addition of water, the bottle is immediately closed and shaken forcefully to ensure proper dispersion and emulsification.• This process is continued until all the required water has been added and a uniform primary emulsion is formed.• Once the primary emulsion is obtained, other ingredients such as preservatives, sweetening agents, or flavoring agents are added.• These ingredients are mixed gently to avoid breaking the emulsion.• The final emulsion is made up to the required volume and transferred to a suitable container.AdvantagesThe Bottle Method is especially useful for emulsifying volatile oils, as it minimizes exposure to air and reduces the loss of volatile components. It requires only simple equipment, making itconvenient for small-scale or on-the-spot preparations. The method is easy to perform and does not require advanced technical skill.DisadvantagesThis method is not suitable for viscous oils, as such oils do not disperse efficiently by shaking alone. The emulsions produced by this method may have a less uniform droplet size comparedto those prepared using mortar-based methods, which can slightly affect the stability and appearance of the final emulsion.Beaker MethodThe Beaker Method is a widely used emulsification technique, particularly suitable when synthetic emulsifying agents such as Tweens, Spans, soaps, and other surface-active agents areemployed. This method is commonly applied in the preparation of pharmaceutical and cosmetic products such as creams, lotions, and emulsified topical formulations where good uniformity andsmooth texture are required.PrincipleThe principle of the Beaker Method is based on uniform mixing of two immiscible phases at the same temperature. Both the oil phase and the aqueous phase are heated separately to anidentical temperature, usually between 70 and 75°C. Heating reduces the viscosity of both phases and lowers interfacial tension, which facilitates better dispersion of one phase into the other.When the phases are mixed at the same temperature, stable emulsification occurs, and the emulsifying agent effectively forms a continuous interfacial film around the dispersed droplets.Procedure• The oil phase is prepared by dissolving all oil-soluble ingredients, including the oil-soluble emulsifying agent, in the required quantity of oil.• The oil phase is heated in a beaker to the specified temperature.• Separately, the aqueous phase is prepared by dissolving water-soluble ingredients and any water-soluble emulsifier in purified water.• The aqueous phase is also heated to the same temperature as the oil phase.• After both phases reach the same temperature, the internal phase is slowly added to the external phase with continuous stirring.• The direction of addition depends on the type of emulsion required, either oil-in-water or water-in-oil.• Stirring is continued steadily to ensure uniform dispersion of droplets.• After complete addition, stirring is maintained while the emulsion is allowed to cool gradually to room temperature.• During cooling, the emulsion thickens and gains stability.• Heat-sensitive ingredients such as perfumes, colors, or preservatives are added during the cooling stage.AdvantagesThe Beaker Method is highly suitable for the preparation of creams and lotions with smooth texture and good appearance. It produces emulsions with fine and uniform droplet size, whichenhances stability and elegance. The method is flexible and compatible with a wide range of synthetic emulsifying agents.DisadvantagesThis method requires careful temperature control, as uneven heating of the two phases can lead to poor emulsification or phase separation. It is not suitable for heat-sensitive drugs oringredients that may degrade at elevated temperatures. The process also requires additional equipment such as heating arrangements and stirring devices.In-Situ Soap Method (Nascent Soap Method)The In-Situ Soap Method, also known as the Nascent Soap Method, is a special emulsification technique in which the emulsifying agent is not added separately but is generated during theprocess of emulsification itself. This method is commonly used in pharmaceutical and cosmetic preparations where soap formation is feasible and desirable.PrincipleThe principle of this method is based on the chemical formation of a soap at the oil–water interface. A fatty acid present in the oil phase reacts with an alkali present in the aqueous phaseto form a soap by saponification. The freshly formed soap, known as nascent soap, has high surface activity and immediately adsorbs at the oil–water interface. This reduces interfacialtension and forms a protective interfacial film around the dispersed droplets, thereby stabilizing the emulsion. The type of soap formed determines the type of emulsion produced.Procedure• A suitable fatty acid such as oleic acid is completely dissolved in the oil phase.• In a separate container, an appropriate alkali such as sodium hydroxide, potassium hydroxide, or calcium hydroxide is dissolved in water to prepare the aqueous phase.• The oil phase and aqueous phase are then mixed together with continuous stirring.• During mixing, the fatty acid reacts with the alkali at the oil–water interface.• This reaction leads to the in-situ formation of soap at the interface.• The freshly formed soap acts immediately as an emulsifying agent.• Emulsification occurs due to the action of the soap formed at the interface.• Stirring is continued until a uniform and stable emulsion is obtained.Type of Emulsions FormedWhen sodium or potassium hydroxide is used, sodium or potassium soaps are formed, which are water-soluble and preferentially stabilize oil-in-water (O/W) emulsions. When calcium hydroxide isused, calcium soaps are formed, which are oil-soluble and tend to stabilize water-in-oil (W/O) emulsions.AdvantagesThis method produces relatively stable emulsions due to the formation of fresh soap with high emulsifying efficiency. It eliminates the need for adding an external emulsifying agent, simplifyingformulation. The method is economical and effective for suitable systems.DisadvantagesThe application of this method is limited to formulations that are compatible with soaps. The emulsions formed are sensitive to changes in pH and the presence of electrolytes, which candestabilize the system. Additionally, this method is not suitable for formulations containing ingredients that may react adversely with alkalis or soaps.Mechanical MethodThe Mechanical Method is an advanced emulsification technique that employs mechanical energy to reduce the size of dispersed phase droplets. This method is widely used in pharmaceutical,cosmetic, and food industries, especially for large-scale production where high stability and uniformity of emulsions are required.PrincipleThe principle of the Mechanical Method is based on the application of high shear forces. When an emulsion is subjected to intense mechanical stress, large droplets of the dispersed phase arebroken down into much smaller droplets. The reduction in droplet size increases the total surface area, allowing the emulsifying agent to form a more effective and uniform interfacial film.Smaller droplet size minimizes coalescence and creaming, thereby improving the stability of the emulsion.Equipment UsedVarious mechanical devices are employed to generate high shear forces. Homogenizers force the emulsion through narrow gaps under high pressure, causing droplet disruption. Colloid mills use acombination of shear and friction between rotating surfaces to reduce droplet size. High-speed mixers and blenders create intense turbulence and shear, leading to efficient dispersion of theinternal phase.Procedure• Initially, a coarse emulsion is prepared using a conventional method such as the dry gum, wet gum, or beaker method.• The coarse emulsion is then passed through a suitable mechanical device like a homogenizer or colloid mill.• During processing, high shear forces are applied to the emulsion.• These forces break down large droplets into finer and more uniform droplet sizes.• The processed emulsion is collected after passing through the equipment.• If required, the emulsion is passed through the device multiple times to achieve the desired droplet size and consistency.• The final emulsion shows improved physical stability and a uniform appearance.AdvantagesThe Mechanical Method produces emulsions with very fine and uniform droplet size, resulting in excellent stability and resistance to phase separation. It is highly suitable for large-scale andindustrial production, ensuring reproducibility and consistency between batches. The method is efficient and adaptable to a wide range of formulations.DisadvantagesThe major limitation of this method is the high cost of equipment and maintenance. The intense mechanical forces and heat generated during processing may cause degradation of heat-sensitiveor shear-sensitive drugs and other ingredients. Careful control of processing conditions is therefore essential.Ultrasonic MethodThe Ultrasonic Method is a modern emulsification technique used to produce extremely fine and uniform emulsions. It is particularly useful when very small droplet size is required, such as inpharmaceutical, cosmetic, and advanced formulation systems. This method employs high-frequency ultrasonic waves to achieve efficient emulsification.PrincipleThe principle of the Ultrasonic Method is based on cavitation. When ultrasonic waves pass through a liquid medium, they generate alternating high-pressure and low-pressure cycles. During thelow-pressure phase, microscopic bubbles or cavities are formed, which rapidly collapse during the high-pressure phase. The collapse of these bubbles releases intense localized energy and shearforces. These forces break the dispersed phase into extremely small droplets, resulting in a fine and highly uniform emulsion.Procedure• The oil phase and aqueous phase are mixed together with a suitable emulsifying agent to form a preliminary mixture.• The preliminary mixture is subjected to ultrasonic energy using an ultrasonic probe or ultrasonic bath.• Ultrasonic energy is applied for a controlled period based on the formulation and desired droplet size.• Continuous or pulsed ultrasonication may be used to prevent excessive heat generation.• During ultrasonication, droplet size is progressively reduced.• A fine and stable emulsion is formed as a result of droplet size reduction.• After ultrasonication, the emulsion is allowed to cool if required.• The final emulsion is transferred to a suitable container.AdvantagesThe Ultrasonic Method produces emulsions with extremely small droplet size and a high degree of uniformity. Such fine emulsions show improved physical stability and enhanced performance.The method is highly effective even with difficult-to-emulsify systems.DisadvantagesThe main limitations of this method are the high cost of ultrasonic equipment and the generation of heat during ultrasonication. Excessive heat may adversely affect thermolabile or heat-sensitive substances, so careful control of processing time and conditions is required.0369121815hydrophobic(oil soluble)hydrophilic(water soluble)Water DispersibleKey exam points to remember:• Higher HLB value → more hydrophilic• Lower HLB value → more lipophilic• O/W emulsions generally require HLB > 10• W/O emulsions generally require HLB < 6Hydrophilic–Lipophilic Balance (HLB) ScaleHistory of the HLB ScaleThe HLB concept was introduced in 1949 by William C. Griffin, a scientist working with the Atlas Powder Company (later Atlas Chemical Industries).Griffin developed the HLB system while studying non-ionic surfactants, particularly polyoxyethylene fatty acid esters.Before the HLB system, the selection of emulsifying agents was largely based on trial and error, which was time-consuming and unreliable. Griffin’swork provided a quantitative and systematic approach to emulsifier selection, which quickly became widely accepted in pharmaceutical, cosmetic, andfood industries.Later, the HLB concept was expanded and refined by other researchers, including Davies, who introduced group contribution methods to calculateHLB values more precisely.Definition of HLBHLB is defined as a dimensionless number that indicates the balance between the hydrophilic and lipophilic portions of a surfactant molecule.• Low HLB value → more oil-soluble (lipophilic)• High HLB value → more water-soluble (hydrophilic)The HLB scale generally ranges from 0 to 20, although some modern surfactants may slightly exceed this range.HLB Scale and ClassificationEach range of HLB values corresponds to a specific pharmaceutical function:• HLB 1–3 → Antifoaming agents• HLB 3–6 → Water-in-oil (W/O) emulsifiers• HLB 7–9 → Wetting agents• HLB 8–12 → Oil-in-water (O/W) emulsifiers• HLB 13–15 → Detergents• HLB 15–18 → Solubilizing agentsThis classification helps formulators choose the correct surfactant for a desired purpose.Calculation of HLBFor non-ionic surfactants, Griffin proposed the following equation:HLB = (Mh / M) × 20where:Mh = molecular mass of the hydrophilic portionM = molecular mass of the whole moleculeA higher proportion of hydrophilic groups results in a higher HLB value.Davies later introduced a more detailed method using group numbers, especiallyuseful for complex surfactants.Relation Between HLB and Type of EmulsionThe HLB value of an emulsifier determines the type of emulsion formed, in accordance with the Bancroft rule.• Emulsifiers with high HLB values preferentially form oil-in-water (O/W) emulsions, as they are more soluble in water.• Emulsifiers with low HLB values preferentially form water-in-oil (W/O) emulsions, as they are more soluble in oil.Thus, HLB acts as a predictive tool for emulsion design.Required HLB (rHLB)Each oil or lipid used in formulations has a specific required HLB value, which represents the HLB needed to emulsify that oil effectively in a particular type of emulsion.If the emulsifier system used matches the required HLB of the oil, the emulsion formed is more stable.Often, a blend of two surfactants is used to achieve the desired HLB:HLBmix = (HLB₁ × %₁ + HLB₂ × %₂) / 100This blending approach is widely used in pharmaceutical and cosmetic formulations.Uses of HLB Scale in PharmacyThe HLB system has extensive applications in pharmaceutical formulation:• Selection of suitable emulsifying agents for O/W and W/O emulsions• Design of stable oral, topical, and parenteral emulsions• Selection of wetting agents for suspension formulations• Choice of solubilizers to improve aqueous solubility of poorly soluble drugs• Development of creams, lotions, ointments, and gels• Optimization of self-emulsifying drug delivery systems (SEDDS)• Reduction of formulation trial-and-error during product developmentExamples of HLB Values of Common Emulsifiers• Span 20 → HLB ≈ 8.6 (W/O emulsifier)• Span 60 → HLB ≈ 4.7 (W/O emulsifier)• Tween 20 → HLB ≈ 16.7 (O/W emulsifier)• Tween 80 → HLB ≈ 15.0 (O/W emulsifier)• Lecithin → HLB ≈ 8 (variable, depends on source)A suspension is a heterogeneous liquid dosage form in which finely divided insoluble solid particles are dispersed uniformly in a liquid medium. The solid particles do not dissolve but remain suspendedthroughout the vehicle, and they may settle down on standing due to gravity. However, these particles can be easily redispersed by gentle shaking to restore uniformity before use. Suspensions arecommonly used in pharmaceutical preparations to administer drugs that are insoluble or unstable in solution form, ensuring accurate dosing and improved stability.SuspensionProperties of a Good Suspension • Solid particles should be uniformly distributed throughout the dispersion medium so that each dose contains the correct amount of drug.• Particles should be small and of uniform size to reduce rapid settling and to provide a smooth and elegant appearance.• The suspension should have a slow sedimentation rate.• It should not form a hard cake on standing.• Any sediment formed should be easily redispersed by gentle shaking.• The viscosity should be suitable to keep particles suspended without causing difficulty in pouring or administration.• The preparation should be physically stable throughout its shelf life.• It should be chemically stable and not undergo degradation during storage.• The suspension should be microbiologically stable and free from contamination.• It should be palatable, non-irritant, and acceptable in taste.• The color and odor should be pleasant and acceptable.• The suspension should be free from grittiness.• It should be easy to pour and measure accurately.Suspensions Advantages of Suspensions• Improved bioavailability compared to tablets and capsules because the drug is present in a finely divided state with increased surface area for dissolution and absorption.• Faster onset of action than many solid dosage forms.• Better chemical stability than solutions for drugs that degrade rapidly in dissolved form.• Suitable for drugs that are poorly soluble or insoluble in water and cannot be formulated as solutions.• Ability to deliver high drug concentrations when solubility is limited.• Flexible dosing, allowing easy dose adjustment, especially useful for pediatric and geriatric patients.• Easier to swallow than solid dosage forms, making them suitable for pediatric, geriatric, and dysphagic patients.• Better taste masking of unpleasant drugs compared to solutions.• Can provide a soothing effect on irritated tissues when administered orally or topically.• Relatively simple and economical to prepare compared to some other dosage forms.Disadvantages of Suspensions • Physically less stable than solutions and may undergo sedimentation, caking, or crystal growth during storage.• Accurate dosing may be difficult if the suspension is not shaken properly before use, leading to dose variation.• Bulkier and less convenient to transport and store compared to solid dosage forms.• May have an unpleasant taste or gritty mouthfeel, reducing patient compliance.• Preparation is more complex than solutions and requires suspending agents.• Require preservatives to prevent microbial growth.• More susceptible to microbial contamination than solid dosage forms.• Generally have a shorter shelf life compared to solid dosage forms.Classification ofSuspensionsBased on generalclass / route ofadministrationBased onproportion of solidpresentBased on natureand behavior ofsolid particles