Physical Pharmaceyy ny 72 rail” CHAPTER Coarse Dispersion SU da Ee 4.1.1. Introduction oe A coarse dispersion in which insoluble solids are suspended ina liquid Medium is termed as pharmaceutical suspension. Suspensions are biphasic liquid preparations containing finely divided 0.5-5.0n solid drug particles (discontinuous phase) dispersed or suspended throughout a liquid or semisolid vehicle (continuous phase). Suspensions are intended for oral administration, external application, or parenteral use. ° An ideal suspension should possess the following properties: 1) The solid drug particles should not sediment frequently. On slight shaking of the suspension container, the sediment should immediately re-disperse. 2) The particles should not sediment to form a cake. 3) The suspension should be viscous enough to allow its easy pouring. 4) Itshould be chemically stable. 5) It should be palatable enough to be used intemally, whereas, for extemal application it should not contain gritty particles) 4.1.2. Classification Suspensions can be classified: 1) On the basis of their general classes: eR fi 7: i) Oral Suspensions: These are meant for oral administration in which one or more insoluble medicaments are dispersed in the liquid yehicle. | ii) Externally Applied Suspensions; ‘These are meant for topicél application. iD, Be iii) Parenteral Suspensions: These are heterogeneous systems in which the solid phase is dispersed within a liquid phase, : 2) On the basis of the proportion of solids; naps i) Dilute Suspensions: These comprise Of 210%6W. @.g., cortisone acetate and prednisolone acetate, ii) Concentrated Suspensions: T! comprise concentration as high as 0° 4 application of zinc oxide and Tespectively. of solid constituentsDispersion (Chapter-4) 7” 2B On iy ea welce Nature and behaviour of Nid: g) Froccula uspensions: solids: \ between the particles to fo These systems involve chemical bridging regation ae ight and fluff " cumple flocculat facilitated through adding flosculating agent “me ee ton can be attained by addin 8 agents. For positively charged deflocculated ig extra anions to a Suspension, Deflocculated Suspensions: particles. In comparison to deflocculated suspensions also slower rate. Deflocculated suspet life. These systems have rel; flocculated systems. These systems contain free solid the flocculated suspensions, the undergo aggregation but at a much nsions generally have a shorter shelf- atively greater bioavailability than ,1.3. Flocculated and Deflocculated Suspensions solid drug is crushed into smaller particles and then dispersed in a dispersion dium in order to prepare a suspension. As a result of crushing, the surface area particles and their associated surface free energy increases. This makes the tem thermodynamically unstable with highly energetic particles which oup and reduces the total free surface energy. herefore, the particles dispersed in the liquid suspension form light, fluffy occules held together through weak Van der Waal forces. the presence of stronger adherent forces, the particles are known to form sregates. So, flocculation may result in aggregation. the free surface energy (AF) of particles ; . ive is reduced fter the particle size is reduced, (AA). This can be expresse a eases with increase in their surface area AF= y- AA . Ni eae : aie oe a permeate here, 'y = Interfacial tension between liquid medium paacreS suspension can attain thermo ) Decreasing the interfacial ) Reducing the total surface af The second method is rarely € ceutical suspensions. O! Dbserved since the agent gets the particles should come.rm mn sical Pharmacy, J resence of an electrical potential of the Surr, 0 harge due to the following reasons; "tly, . ‘ «ve forces arise in the pt Ea . ce icles acquire a ¢ 1) Surface ionisation of the molecules, An -_ 2) Tons can adsorbed by the particles intl ie surrounding liquid, or 3) A difference existing between the dielectric constants of the ¢j medium and the dispersed particles. Pein Zeta potential is known to exist at the particle surface. In case of hj ntial, the attractive Van der Waal forces surpass the repulsive hgh 244 forces between the two particles. etic s are dispersed in this manner. Besides lower dsorbed ion carrying a charge opposite to tha The deflocculated particle: tralise the surface potential. zeta potential, addition of an a the particles is also known to neu! Repulsion curve Ww suspensio Particle “Attractive curve Distance between particles; Figure 4.1: Potential Energy Curves for Particle Interactions in Suspensions At a certain concentration of the added ions, the attraction forces are known to exceed the electrical forces of repulsion. Hence, the molecules closely interact with each other and tend to form floccules. This sort of system is known as @ flocculated system. i VV.Curve ! «Zeta potential: 1pspession (Chapter) poweve® whe gurfacl® tion pecan agent role, e.g, fl cculation ¢ table 4.1 signifies the differentiating points betw. fiocculated suspensions: ra flocculating agent is added contin tential may Increase in Opposite directi Flocculating agents usually comprises of ats. Figure 4.1 generally depicts the energ electro} ed approach. Figure 4.2 presents the role of monobasic i i . Otassi of a bismuth sub-nitrate suspension, Potassi 75 ously in hj on and m; ih conce ‘nitration, AY reversy i © the above ¢ les, Polymers, Y peraim Presenting the above & diagram depicting the ‘um phosphate in the een deflocculated and Table 4.1: Difference between Deflocculated and Flocculated Suspensions Deflocculated Suspension Flocculated Suspension 7 Pas duped paces | yur at tie ed ler spe Cloudy supernatant is obtained. A clear supernatant is obtained. Repulsive forces exist between the | Attractive forces exist between the particles. particles. Particles form separate entities. Particles form loose aggregates, Sedimentation rate is slow as the particle size is small. Sedimentation rate is high as the flocs are a collection of smaller particles (higher size). Particles _ settle separately. independently — and Particles settle as flocs. The sediment is closely packed, thus, forms a hard cake. The sediment is loosely packed, thus, does not forms a hard cake. Re-dispersing the hard cake is not possible. Re-dispersing the sediment is easy. In the potential energy curves, it represents the primary minimum. In the potential energy curves, it represents the secondary minimum. Achieves comparatively low Achieves high bioavailability. sme us bioavailability. 4.1.4. Interfacial Properties of Suspended Particles Two important interfacial properties of suspensions are: 1) The surface free energy, and i icles. 2) The presence of electric charges on the surface of the dispersed particles 414.1. Surface ‘ s When solid or liqui Teadily leading to con ‘ area jnereases AF & AA AF = ys..AA Where, ‘You = Interfa] a Physical Pharmaccutie This makes the em thermodynamically unstable. Thermodynamic insta neans that the particles are highly energetic and tend to re-group in such a wa 4S to decrease the total surface area thereby reducing the surface free energy, The particles in liquid suspension therefore tend to flocculate. The extent of the formation of floccules can be taken as a measure of the system 10 reach thermodynamically stable state. Increased stability can be realised by reducing the ee ea decreasing the interfacial area. Interfacial tension can be ret vecithin a are of certain surface active agents, e.g., sodium lauryl sulp! a interfacial eae are adsorbed selectively at the interface thereby reducing | rained ‘Ion, While the particles remain dispersed or defloceulated and seite relatively slonly, they may form a hard cake at the bottom of the container w! tually difficult to re-disperse. 4.1.4.2. Surface Potential ; ; Though suspensions consist of uncharged particles suspended in an uncharged medium, the solid particles frequently acquire a positive or a negative charge and the vehicle around it will contain the same charge (the so-called gegenions with ‘opposite sign, so as to maintain electroneutrality). ‘The forces at the surface affect the degree of flocculation and aggregation. Each particle is associated with an electrical double layer which gives rise to the zeta potential. The importance of zeta potential with regard to the stability and nature of flocculated suspension is best appreciated by noting the forces between the ) particles in suspension. ‘epulsive curve ” Energy of interaction Distance of separation Attractive curve Figure 4.3: Potential Energy Curves for Particle Interactions in Suspension The potential energy of two separation (figure 4.3). The Particles is plotted as a function of the distance of of repulsion, and the net C gy of attraction, the eners! een the particles“ersion (Chapter?) pis? , ge; on the other hand ther € will F © that the net potential wil I be Van der Waale Will be the sum of the 1s Very close together 00-200nm (secondary » former © nergy E; is large and if those partictes co; eo to separate again and caking results. If they can oe ee minimum they are again in equilibrium (flocculation), but the particle secondary Mp easy to break apart, Thus, flocculated suspensions are characterised oe in the secondary minimum and being voluminous they form loosely ey | the giticw! sediments. However, if the particles pack into compact sediment they are closer and experience a pressure allowing them to pass the energy barrier and enter the ‘imary minimum causing caking. Thus, caking results in either deflocculated or poorly flocculated systems. The potential existing in the system responsible for repulsion is the zeta potential. If the zeta potential is high the particles repel one another and remain in a dispersed form for a long time, i.e., they settle slowly. Even when brought closer during random motion or agitation the deflocculated particles resist collision due to the high surface potential. Such a system is said to be deflocculated. If the zeta potential is low, or is lowered by the addition of preferentially adsorbed ions whose charge is opposite in sign to that on the particles, the electrical forces of repulsion are lowered sufficiently for the forces of attraction to predominate. Under such conditions, the particles may approach each other more closely to form loose aggregates termed flocs. Such a system is said to be flocculated. 4.1.5. Settling in Suspensions he ideal properties of suspensions indicate t ul Particles should be prevented, Thé study of sedimentation theorit ves information related to the factors affecting the settling of particles. These aces ie ‘ factors allow the pharmacist to take suitable acti Suspensions, bays : jon for manufacturing ss. Theory of Brownian Moe of part °edimentation is prevented by the Brownian movemen! ity: 1 suspension are Taree in 3 and also the medi D- re NaN oe nt rownian motion “gre favourable the 7 i 5 «Particles are not in a state of Bi icles, The particles thus, les the ao and also the particle densi “NCES are found to be in a state of E8 Physical Pharmacy Hy 4.1.5.2, Theory noite of Sedimentation beans the St The rate of sedimentation of particles is expressed through the Stokes Law py using the given formula: se) ‘i ; d Rate of sedimentation =- Where, d = Diameter of the particles (em). 4 hase (g/er). 1 = Density of the dispersed phase 4 2 = Density of the dispersion medium tefem 1 = Viscosity of the dispersion te ree. g = Acceleration due to gravity (980.7 ¢ vest i ich Stokes law is applicable: ; we as meet particles are irregular in the suspension, This condition is fulfilled by 2) Particles should settle do rn pestis in pet ‘oom; whereas dis trations of 5-10% or more, dilute suspensions having_0. : ids ii i t in concent solids in most suspensions are present in ct c ‘ Solids exhibit hindered settling, i... particles interfere with the free settling Stokes law is not applicable of other particles, in these suspensions. Hence, to these types of suspensions. tems, where particles settle down ‘ed to deflocculated sys e } seful in fixing the following factors used in the Following are the conditi 1) Particles should be sphet Stokes law is connect freely. But, this law is us formulation of suspensions: 1) Particle Size: On reducing the particle size to sedimentation rate is decreased. by a factor of particles undergo rapid absorption. \, Medium: The suspensions should be of optimum viscosity. Equation (1) indicates that increasing viscosity lowers the sedimentation rate. The medium of high viscosity has the following advantages: | 7 i) It enhances the physical stability by reducing sedimentation. ii) It inhibits crystal growth by reducing movement of particles. iii) It prevents the metastable crystals to convert into stable crystals. half of its original size, the “four [equation (1)]. Smaller 2) Viscosity of the The medium of high viscosity has the following disadvantages: i) It obstructs the redispersibility of the sediment. ii) It retards drug absorption from the suspension. iii) It creates problems in material handling during suspension manufactur- , d in pharmacy. ual, the rate ol edium density is am betwee! 3 yylpyrrolidon® ine, etc.2 = 41.6. Formulations of Flocculatea suspensions and Deflocculated ‘ormulation of a suspension Possessi "1 ' ae the particles in suspension “ae to be eal Stability depends on flocculated. First approach involves use of a renee aa : Or to remain fl occulated particles in Suspension; a sécond iiss 4 vehicle to keep occulation as a means of Preventing cake formation. A third ‘ o Controlled first and second method, results in a product with optimum stably of schemes are illustrated in figure 4.4 'Y. The various Addition of wetting agent and dispersion medium Uniform Dispersion of Deflocculated Particles A B Cc | | | Incorporation of Addition of Addition of structured vehicle flocculating agent flocculating agent Flocculated Flocculated Suspension Suspension as Final Product Deflocculated Incorporation of Suspension in structured vehicle Structured Vehicle as Final Product Flocculated Suspension in Structured Vehicle as Final Product Figure 4.4: Alternative Approaches to the Formulation of Suspensions 4.1.6.1. Dispersion of Solids . In dispersion process, the solids and water (vehicle) are in intimate contact. It is a Critical and dit step ial ids mostly are jobic. Finely divided that is hard to , however their pel. Due to ff densities are hi lene glycol) are s of wetting ofPhysical Pharing 4 at MAce 80 Muy ticles and completely separates them during the mixing Process, solid particles a icles a ater , it instantly surrounds the particles and yeti iscil vith glycerine, thus it n ; vt isc ve nitial step of dispersing the solid particles. The ame This the initial step of dispersing : detlocculated in the vehicle at this state. Voids (air) or Oma comige Po MOO 0 contact ae eral Glycerine Glycerine in voids coating Oo J ‘Separation Grae Q oe =“ Aue — ae Ge Figure 4.5: Steps Involved in the Wetting Process of Solids by Glycerine Surfactants help in the dispersion process by decreasing the inte between the solid particles and the vehicle. This reduces the contact angle anj displaces the air from the solid surface. Surfactants lying in the 7-9 HLB Tange are used as wetting agents. Surfactants produce a large amount of foam and ths create problems during mixing; therefore should be used in a minimum amount, facial tensigy 4.1.6.2. Structured Vehicles - Deflocculated Suspension (_Pseudoplastic or plastic rheologic behaviour are shown by. the structei vehicles. These vehicles should also possess some degree of thixotropy (ic, gt sol-gel transformation), as this increases the physical stability of suspensions. 4 shear thinning system obtains a gel-like structure during storage, and this te Particles do not settle down {Viscosity reduces and the suspension becomes ast when shaken, hence unifo1 dispersion of solids is achieved. |Better pourilt and consistent doses are even The suspension attains back its gel-like struct when left undisturbed.(Structured vehicles are used for the preparation deflocculated suspensions,\ a \ Suspensions for oral use have non-i amounts) due to the Parenteral use havi bentonite are effe, and ionic strengtl methylparaben at growth. nic type suspending agents (in i Presence of high amounts of solids.) Suspens © suspending agents in 0.5% w/v concentration. ee tive (at 2-5% w/v concentration) based upon the os ( h. If clays are used as suspending agents, preserval! i ue nd propylparaben) should be added as clays stimula! “D roid” adding polyviny!eb™«persion (Chapter-4) cot pispersion Controlled Flocculati 1.6.3+ : lation - Floccul: pet the LTE Sante Wetted and daperved by a edgar, . gccurs slow fe ‘ Sees een Agents (e.g., electrolytes, ihe eculation Riymers) The advantages of the flocs are that they donot form had cakes and ease the re-dispers ie sediment. The following methods are u ed es and proceulan o real particles tao sed to attain The dispersed partic'es mostly carry a surfac pry D jecreased by adding oppositely charged an ag tn is Consequently, zeta potential is reduced and particles form att Pe ytes). petween the adjacent particles, ‘ attractive forces 81 2 Surfactants and polymers (ong chain compounds) adsorb a part of their chains on the particle surface and project out the residual part into the medium. This bridging helps in the formation of flocs. electrolytes On dispersing bismuth subnitrate in water, the bismuth particles undertake a large positive charge or zeta potential (25mV or more). The like charges on the icles experience repulsive forces, thereby making the system deflocculated. Particles resist collisions even when they are brought together by agitation. If small amount of a flocculating agent (e.g., monobasic potassium phosphate) is added in the above suspension, the negatively charged phosphate ions adsorb on the positively charged bismuth particles. , The repulsion forces reduce and the attractive forces start ‘to operate; and consequently, the positive zeta potential reduces and the solids start forming flocs (figure 4.6). This can be established from the maximum sedimentation volume. The zeta potential reduces and becomes zero when more electrolytes were added. In this stage also the suspended particles persist as flocs. sume Negative Flocs orption of Pee to this, the in experience Pulsive forces,aa 7 Physical Pharmace 6 sete. Surfactants id dispersion by decreasing the interfacial tens; Surfactants Ceara Mjeflocculating agents. Therefore, the su ey woe eateation &8 of much importance for attaining flocculation, Atay J a ionic surfactants (e.g., sodium lauryi sulphate and sodium viphosnecinats) are used, the head portions get adsorb on the solid Surface the tails project outwards to form bridges between the particles. This Arrange, causes flocculation and stops solid Precipitation (figure 4,7), Non Men, surfactants (e.g., Tweens) also undertake a partial negative charge in “TOhig dispersion and form a network between the particles. *Ueo4, ioc, d PANRAAS Se Figure 4.7: Flocs Formed by Surfactants Polymers Polymers act as flocculating agents, thus a Part of the polymer chain adsorbs on the particle surface and the temaining part projects out into the dispersion medium (figure 4.8). For example, the sedimentation volume of sulphaguanidine suspension is increased by xanthan gum (anionic heteropolysaccharide) via bridging. Solid particle Polymer molecule QO Flocs Figure 4.8: Flocs Formed by Polymer Bridging 4.1.6.4. Flocculation in Structured Vehicles clear; a ¢ ion suspension rapidly bere tty sa jicles.rsion (Chapter-4) (Oy @) sure) © (-RNH;") Anionic (-) @>—" @x @ © a 2, 2B Uncoated particles Coated particles EXO (positively charged, 8) negatively charged ‘or neutral particles) Flocculated Suspending] particles agent (-) |\$—_——>| ook Suspension of flocculated “Finished Particles before adding guspension suspending agent 83 Dispet Figure 4.9: Events Involved in the Formation of. ‘Stable Suspension luires the addition of a Positively charged ulating agent or ion; in the Presence of such a material, the negatively ‘arged suspending agent may Coagulate and lose its suspendability, . particles that bear a Positive charge, as the gative flocculating agent that the formulator must employ is compatible with e similarly charged suspending agent. 1.7, Pharmaceutical Applications 'e applications of suspensions are as follows: ) They are used either for avoiding drug damag Stability, eg., oxytetracycline suspensions. ) They are C i e or for improving drug on obnoxious tas y in drugs, e.g. calamine ministered as 6) Some X-ray :Physical Pharmaceutics 84 4.2. EMULSIONS uction oo ae Sit aes containing two immiscible fails ee of which is en T sed as minute globules into the other, is termed asp) armMaceutica, smutsion The liquid in the form of minute globules is the dispersed : wile the liquid containing the dispersed globules is the continuous phase, i i i immiscible liquids for a proton, lsifying agent is added to disperse two immisci f a c ame “period. This agent covers the globules to scatter them indefinitely jn the continuous phase, resulting in a stable emulsion. The diamecer of globules in an emulsion lies in the range of 0.25-25um, The coarse emulsions’ are known to contain large-sized globules, whereas fine emulsions are known to possess globules of mean diameter below SUM. The micro-emulsions are known to possess globules of diameter as small as 10nm, and are milky and transparent in appearance. 4.2.2. Classification Depending on their dispersed phase, emulsions can be categorised into: 1) Water-in-Oil Emulsions: In these emulsions, the water (dispersed or internal phase) is dispersed as globules in the oil (continuous phase or dispersion medium). For example, butter and salad dressings. The water is in the dispersed Phase and oil is in the continuous phase in w/o emulsions. Usually, these emulsions are applied topically as lotions and creams. These emulsions also provide emollient action, Wool fat, resins, bees wax, synthetic compounds, and soaps formed from divalent bases (like Ca”, Mg™, and Zn‘) are a few emulsifying agents used for preparing wlo emulsions. 2) Oil-in-Water Emulsions: In these emulsions, the oil (dispersed or intemal phase) is dispersed as globules in the water (continuous phase or dispersion medium). Examples of o/w emulsions meant for both internal and external use are: i) External: Benzyl benzoate emt hexachloride emulsion (Seaboma), ii) Internal: Vitamin A in c (Agarol), Griseofulvin in coy ulsion (Ascabiol), gamma benz etc. om oil in water, liquid paraffin in wat! m oil in water, etc, iii) Microemulsions; These emulsions ——~“around 0.0),4m. Globules of such and are invisible to the naked ey , sie are known to contain globules gh sizes are incapable of retract ©; thus, microemulsions are tansPi r ticles are in aS!coarse Dispersion (Chapter-4) 85 iv) Fine Emulsions: These emulsions are ki f i appearance and contain globules 0f0.25-251m. pe dl uw a einieeeel pee emulsions are generally referred to as emu! - -emulsion. In an oil-in-water-in-oil (o/ ion . . : 7 -in- ‘w/o) emulsion, very small oil droplets are dispersed in water globules of a water-in-oil emulsion; while ina water-in-oil-in-water (w/o/w) emulsion, water droplets are dispersed in the oil phase of an oil-in-water emulsion. Multiple emulsions are prepared in two stages. For example, 2 w/o/w emulsion is prepared by forming a water-in-oil system (primary emulsion); then this system is dispersed in a second aqueous phase. Multiple emulsions are used for delivering sustained release dosage forms since the drug in the innermost phase passes through two other phases and then gets released for absorption. 4.2.3. Theories of Emulsification Emulsification is the method of dispersing a liquid in another immiscible liquid. The major groups of emulsifying agents are soaps, detergents, and compounds whose basic structure is a paraffin chain ending in a polar group. Bancroft stated that the essential conditions for a stable emulsion are that the drops of the dispersed phase should be small enough to remain suspended and a suitably viscous film should be present around each drop of the dispersed phase to prevent them from combining. Many theories have been introduced to describe the way through which the emulsions are stabilised by the emulsifier. Presently, no such theory has been proposed which can be universally applied to all emulsions. Fischer suggested that a few factors play a role, and the importance of each varies in different - emulsions and also in the same emulsion under different conditions. 4.2.3.1. Electrical Double Layer Theory Negatively charged oil globules are_ present in a pure oil and pure water emulsion. | Water ionises into hydrogen and hydroxyl ions. The adsorption of hydroxyl ions gives the negative charge on the oil globules. These adsorbed hydroxyl ions layer around the oil globules. ii) The viscosity of continuous phase can be improved by adding y, Mey Seq. hancers. «i a e density difference between the two phases should be reduc, i se S) sent in adequate quanti iv) The dispersed phase should be presen quantity, a The emulsion should be stored in a cool place at a low temperature nce: In this condition, two or more globules fuse togeth peaeey aroplets. Hence, the globules lose their individuality. The Fa to fy film is degraded during coalescence, thus, it is an irreversible proces ati not possible to re-disperse the globules even by shaking. 8. Ii Cause: The structural properties of the interfacial film affect menon of coalescence. It usually occurs after the emulsifying Po ent pheno’ peu r s activity or if it is present in inadequate quantity. loses it Remedy: Following steps should be undertaken to overcome Coalescence. i) An adequate quantity of emulsifying agent should be added and Suita emulsifying machinery should be employed in the preparation - emulsions. ii) Precautions should be undertaken while adding emulsifying agents in ite preparation since an unsuitable emulsifying agent loses its activity within a short time period. Breaking and Cracking: These processes involve both coalescence of the dispersed globules and separation of the dispersed phase. The merits of emulsification are lost since it is not possible to redistribute the globules and also precise dosage form is impossible. Cause: Any physical, biological, or chemical effect that modifies the nature of the interfacial film of an emulsifying agent is known to cause cracking. Following physical features are known to cause breaking: i) Opposite Types of Emulsifying Agent: If an opposite type of emulsifying agent is added, emulsification reduces and cracking occurs For example, soaps of sodium lauryl sulphate (monovalent metal) produce an o/w emulsion, whereas soaps of calcium lauryl sulphate (divalent metal) produce a w/o emulsion. The process of adding @ monovalent soap emulsion to a divalent soap emulsion or vice versa call instabilise the emulsion and make them prone to cracking. ii) Addition of Common Solvent; The solvent in which both disperse a continuous phases are soluble can be added to form a single system. ‘ sc iii) Temperaturjon (Chapter-4) aut? pispers a Incorporation of Excess Disperse Phase: An emulsion ig Vv cack if the disperse phase concentration ig More than 14% More liable to 2 ima . lh, i) Inadequate addition of emulsifying agent in the Prepar. cracking ot breaking. “ration also leads to »: Following steps must be underta gre emulsifying agents should be ae in the prepa a i) The temperature at which the emulsions are stored sh n Esl ‘ould be under iii) The concentration of the disperse phase should be regulated. jv) Adequate quantity of emulsifying agent should be added. ‘ culty: Phase Inversion: The phases of an emulsion unde transforms from an o/w emulsion to a w/o emulsion a degradation may be responsible for this Phenomenon. Hi 5 : - How following physical factors are known to affect inversion: overs the i) Alteration in the phase volume ratio of the emulsion, and ii) Cooling those emulsion prepared by heating and mixing of two phases. Tgo inversion when it ind vice versa, Chemical 6) Deterioration by Microorganism: The moulds, yeasts, and bacteria may: i) Degrade the emulsifier, ii) Infect the aqueous phase, and iii) Degrade the oil soluble vitamins. Remedy: This problem can be overcome by adding adequate quantity of preservative in the preparation. Mixture of para-hydroxy benzoates of methyl ester (0.1-2%) and propyl ester (0.02-0.05%) are often used as a preservative. The preservatives with solubility in both the phases of emulsion should be used. If the preservative is not soluble in both the phases, a suitable preservative for each oil and aqueous phase should be used. The preservative to be used should not form any complex with the emulsifying agent and other ingredients. Miscellaneous: Precautions should be undertaken to protect the emulsion against degradation caused by light, temperature, freezing, and thawing. 42.6. P i Emulsions 2.6. Preservations of Emulsio! pee other Preservation of the emulsions can be done by, using antioxidants antimicrobial preservative: seen in many ) Antioxidants: Oxidative changes by microorganist oF animal emulsions containing vegetables and mineral ee occurTilé due t Antioxidants can be used to prevent the atmospheric oxygen. “als, ‘These effects of free radica able Antioxidants may protect the cells against the for it with ee “and compete when the agents have a high affinity for mand esyecies prosuee substances in the formulation. Free radicals a92 2) '’ Physical Ph, hie, | body breaks down food, or by environmental exposures like leh “hy | and radiation, Pree radicals can damage cells, and may play q tole Mg disease, cancer and other diseases, he iy ‘The ideal antioxidant should possess following qualities: i) Non-toxic, ii) Non-irritant, iii) Odourless and tasteless, iv) Effective at low concentration under the expected conditions and use, and v) Soluble in the medium and stable. OF st, Examples of some commonly used antioxidants for emulsified system; i) Alkyl gallate such as ethyl, propyl or dodecyl gallate, Meld ii) Butylated hydroxyanisole (BHA), and iii) Butylated hydroxytoluene (BHT). Antimicrobial Preservatives: It is necessary to preserve the emulsions microorganisms as these can proliferate easily in emulsified systems high water content, particularly if carbohydrates, proteins or ger, materials are also present. Emulsions contain water, which will Suppo microbial growth. Microbes produce unpleasant odours, colour changes and gases and affect the emulsifying agent, possibly causing breakdown of the emulsion, Other ingredients of emulsions can provide a growth medium for microbes For example, arachis oil which supports aspergillus species and Tiguid paraffin which supports pencillium species. Contamination may be introduced from a variety of sources including: i) Natural emulsifying agents, e.g., starch and acacia, ii) Water, if not properly stored, iii) Carelessly cleaned equipment, and iv) Poor closures on containers. Contamination due to microorganisms can result in problems such as: i) Colour and odour change, ii) Gas production, at iii) Hydrolysis, iv) pH change, and y) Eventually breaking of emulsion, : 'se pispersion (Chapter-4) ; soars ; 93 | have a w q y) Should ide spectrum of activity against 2 yeasts, and moulds! Bainst a range of bacteria, , ave high wat ili ‘ vi) Should have ater solubility and a low o corner O/W partiti i vid) Should have bactericidal rather than bacteriostatic cart coetfcient : s a 'y. A preservative with a low o/w partition coefficient: wil concentration in the Aqueous phase. A combination of preservati give the best ae cover for an emulsion system. The ratio. the disperse phase volume to the total volume is known as the ph: Raine phase volume ratio. are nee | have a higher If a preservative is soluble in oil and if the proporti il is i v e in ( portion of oil is increased, th concentration of preservative in the aqueous phase decreases, and vice eal Examples of some preservatives in use are: i) Benzoic acid (effective at a concentration of 0.1% at a pH ii) Esters of parahydroxybenzoic acid such as methyl parsben (003%) iii) Chloroform, as chloroform water (0.25% v/v), : a iv) Chlorocresol (0.05-0.2%), y) Phenoxyethanol (0.5-1.0%), vi) Benzyl alcohol (0.1-3%), vii) Quaternary ammonium compounds (e.g., cetrimide, which can be used as a primary emulsifying agent but can also be used as a preservative), and viii) Organic mercurial compounds such as phenyl mercuric nitrate and acetate (0.001-0.002%). 2.7. Rheological Properties of Emulsions ulsions are estimated for their flow behaviour. The flow related attributes sirable for the performance of an emulsion are: 1) Removal of an emulsion from a bottle or tube. 2) Flow of an emulsion through a hypodermic needle. ) Spreadability of an emulsion on the skin. ) Stress induced flow changes during manufacture (milling, etc.). lute emulsions possess Newtonian flow, thus the comparison of flow curves among various batches can be easily done. However, concentrated emulsions sess non-Newtonian flow, thus their analysis becomes difficult. Multipoint . d for their iscometers (like cone and plate or cup and bob type). are use " Valuation. A rough guide ota to the type of flow obtained based on phase94 Physical Pharmaceutics.t] 4.2.8. Pharmaceutical Applications The wide ranges of pharmaceutical applications of emulsions are: 1) They are used to conceal the unpleasant taste and odour of different oily drugs like liquid paraffin, cod liver oil, castor oil, etc. 2) The o/w type emulsions are known to enhance the drug absorption through GIT. 3) The nutrient oils that are difficult to swallow can be injected intravenously as emulsions. 4) Emollients can be effectively applied as emulsions (like cold creams, vanishing creams, etc.) on the affected area. 5) Certain topical preparations are prepared in the form of emulsions to facilitate the rubbing of medicaments on the affected area in such a way that they leave a residual medicament film after the solvent evaporates from the affected area, e.g., turpentine, liniment, benzyl benzoate lotion, etc. 6) Certain o/w emulsions like per-florinated hydro-carbons are used for oxygen replacement therapy. 7) Many water soluble antigens and certain drugs are prepared as w/o type emulsions to be given as depot injection (sustain and release). 8) Certain emulsions comprising different radio opaque elements can be used for diagnosis.