TER rue . Introduction « Suspensions Criteria for a good suspension Interfacial properties of suspended particles Flocculation and deflocculation in suspensions Setiling in suspension Brownian movement Effect of flocculation on sedimentation rate Sedimentation parameters Identificatioy Dilution test Conductivity test Dye solubility test Cobalt chloride test Fluorescence test Direction of creaming test Pharmaceutical Applications of Emulsions Theories of Emulsification Monomolecular adsorption Multimolecular adsorption Solid particles adsorption Physical Stability of Emulsions Flocculation and creaming Coalescence and breaking Physical and chemical changes Phase inversions Assessment of stability of emulsions Preservation of Emulsions Preservation from micro-organisms Preservation from oxidation Rheological considerations n of Emulsion Systems « Formulation of Suspensions Wetting of particles Controlled flocculation Controlled flocculation in structured vehicle Rheological considerations + Emulsions * Types of Emulsions Clinwater emulsions Water-in-oil emulsions Multiple emulsions \_teroemulsions Course While the sn sie of the dispersed particles in acol ° 100 um in case of coarse dispersions. yin the size of their dispersed partic i I nm to 1 pm, itis i ispersion ranges from agen and Emulsions are (WO types of Ci dispersions differ from colloidal dispersion main! 4671468 Physical Pharmacy ‘SUSPENSIONS pension may be defined asa RISES epsom ne person in whic nse oN Hed, 4) spent ble solid particles are wipe a eoarse disper i aspen #acous a0 pcansof sopra insoluble and often dyn so + ramphcrisol is ser Der CANOE Be gy gh iq medium SusPe co for that is pleasant insoluble salt can be formulated as asi pen pol e evoramphenic! palmate ote CHHFONEASS Teg diapered we eM ay ie arte area also allows good adsorptive or nes ig suitable foe pacdia ing for dissolution anda jon oFeertain crs stl absorption. The hig has kaolin. Iso suitable for parenter weakin, When used parenteralls. St jesium carbonate, et. al and ophthalmi ns purposes and ae ass i nerlly providea prolong a Saco application from ssich the drug dissolves Svs apy aon sample of suc a preparation, Certain drugs sighs Tatyon ean be formulated as suspensions non-agiggs Aqueous suspen for topical appication 10 Wy forming a depot inc suspension 18 2 act sorted. Inst Zi “antibiotics which are unstable #34 stable product salvents to provi Criteria for a Good Suspension ‘goo suspension shoud usally posses the flowing desirable properties ster sould not settle rapidly ovinah settle should not forma hard cake and should redisperse easily onsale (4) Suspend: Gi) The particles ing, (iit) A.good suspen (iv) Incase of parente (0) Suspension for external application s jon should not be too viscous to pour, jon should flow out of syringe needle should ao ral preparations the susp ould be easy to apply and not run off. Alsat dey off t00 quickly, (vi) A good suspension should have a smooth, elegant appearance. (v1) It must have an acceptable colour and odour. (viii) It must be resistant to microbial attack. olyse or degrade too rapidly or undergo chars (ix) The suspended ingredients should not hydro polymorphie frm. Ideally, suspensions should be thinotropic, ie. these should become viscous of sui rll ig storage al shoul thin readily on shaking. This prevents sedimentation ofthe drug duri easy withdraw! on shaking. Interfacial Properties of Suspended Particles In considering the interfacial properties of suspended particles two factors must be she intoaee® area of 05 These are the surface free energy increase resulting from the increase in surfacCoarse Dispersions tep reduction in the size of the dye to red #1Ne particles and the presence of te (se ectrical charge on the ce Free ENeraY Melton oF 1SPENSON Works done tra enacts men Ths ‘ 1. particles either fac edsnamicllsuntble by weak van der Waals fore 7 2 light. uly conglomerate th eet er ad essere atc do ener cain sualy ot By the BOW and fusing ogcherofendale ni ae einer ree energy due o reduction of particle siz isgenty theegeaan AG = yg, AA luce the particle size 5 the system thermo late, i. form (i. inctease the surface he 4g isthe increase in work or surface free energy. _ ste interfacial tension between liquid medium and the slid panies. 14 isthe total surface area, Wi excess free energy due to the increase in surface area, the system tends to approach 2 sale sate by reducing the surface free energy’to zero, When the surface free enerey approaches tthe system becomes thermodynamically stable. Reduction in the surface free energy can be scoped either by reducing the interfacial tension or by decteasing the interfacial area ether though Aoeculation (desirable) or aggregation (caking — undesirable). The interfacial tension can ‘etelaced by the addition of a wetting agent which gets adsorbed onthe surface ofthe suspended piles, The Wetting agent is however not able to reduce the interfacial 2spesion generally possesses finite postive interfacial tension as ares ‘ied panicles tend to locculate or aggregate. tension to 2er0 and hence tof which the sus- LEectrical Properties ation in Tete ating om the surface ofthe suspend pics also aft he deere PASE "Ssyetsion, Forces oateaetion arse from van der waa forces while Frese ‘othe interaction of electric double layer surounding each pale. Te : Fi ‘shows the potential ener) of two 22 ofanraction and the potential energy of fepulsc Fig 6 c oni pokes "is pote ay a fumeton othe distance of separation SHOT yoni fsfattraction, the ‘energy of repulsion ‘and the net energy © i alk pe a ‘Shen he repulsive energy is high, the potential baer nt isi pe eet ence, they remait joccul Ae one Prices the approaching particles and hen -, they 7 me partes te nem Pres S¥entually settle, they tend to be closely POEMS! Tb te dispersion i OS the weight of ameter 24 2S eae my come cl aa Mary "ay barrier is overcome a i recive ces hum. As. result, they experi x ultimate170 Physical Pharmacy Energy cure toe foceustegevszonson Ragone (seen ere Enorgyot Anactoncune yon el deocrulated tte ‘Goma amar) Dstarcetetneen ny Fig. 6.1, Potential energy cue for particle interactions in suspension, the original energy barrier, a high energy is required. Hence, re, achieved and the particles emi sediment, To rega ‘vigorous agitation, the redispersion of the particles isnot eas a cake. When the particles are flocculated, the energy barrier is still t00 large to be overcome therefore the particles remain separated by a distance approximately from 1000 to 20004 ig secondary minimum. This distance i sufficient to form the loosely structured floceules, Flocculation and Deflocculation in suspensions The overall charge existing on the suspended particle is the zeta potential and it sa mes indisation of the potentatexistingat the surface ofa particle. Therefore, locculation and def! ‘may be considered in terms of zeta potential. When the zeta potential is high, the repulse fi bberween mo particles exceed the attractive van der waal's forces and the particles remain disper These are then said to be deflocculated. These particles resist eollision. due tothe hgh se Potential even i the particles are brought close by way of random motion or aetation The zeta potential ean be progressively lowered by the addition of an electrolyte who 'sopposits to that of the suspended particles, At some concentration ofthe electrolyte. the anraction dominate slightly over the electrical forces of repulsion. Under these conditions les approach each other and form loose aggregates commonly called flocs. Such a swe sand to be Moseulated . W however, a lane amount of the electrolyte is added, th ene . of the electrolyte is added, the suspended particle ‘opposite charge by adsorption ofthe electrolyte and become deflocculated agai.ine IN SUSPENSION # ot seaimentation ne ato i " 88 ti a on velocity of susp ded pr D Pamilesis piven by Soke mane 7H aecoeding thi 18, se 5 ie ameter ofthe particles in em, i edonsty oF the dispersed phas 1 stvedesity ofthe dispersion medium, easton deo gravity ond 1 ite viseosty ofthe dispersion medium in the rate of settin suhe's law is generally applicable to dilute suspensions conts {sod may not be uniform as particles in eal suspensions vary in sincand top Fp, ~ x P00) Ne sha K isan experimentally determined constant. ‘Thus, according to Stoke's law, the rate of sedimentation of particles ina suspension may be teiced by decreasing the particle size provided the particles are deflocculated The rate of sedi uation can also be decreased by increasing the viscosity ofthe dispersion medium, for example byaddtion of thickening or suspending agents. However, there is an opt sel upto white \wsesity ofthe dispersion medium can be increased since too | much increase in viscosity may hinder {ie utiform redispersion of the suspended particles ater they have setled and ‘would te pose ‘tiem for easy flow of suspension out ofthe container. Another approach esse ss. “thon i to narrow down the difference in the density of the dispersed particles r ae a ®aium, Since the density of the suspended particles is constant fr pics AT i ofthe dispersion medium can be altered to bring it lose aa bes nl ‘eta, the density of the dispersion medium can be increased by ! cin! ethene ely, lycerin, sorbitol, sugar alone oS Smog. Marge spe sn wasdpeneind fy ofthe mia ity of 2.0 Bie montane dein 208 onder having a mean particle diameter of89 BM gp gin of sodium carboxymethy ellos: having #42"472. prysical Pharmacy sate average veo SHER fe tow shear fate was ound ob 30 108 7 Solution eso jim 80° 10 erm Meanpuricle dames) 8 r Acceleration du to grav (e)~ O81 Be? Sedimentation velo y= Spo 1h (60> 10°'(20-1.02)-981 18-50 ‘6200+ 10° -0.98~981 - mo = tes 104 emsee Brownian movement When the size ofthe dispersed particles is very small such as about 2to 5 jum, brownian mets in. However it depends on the density ofthe partiles and the density and viscosity ofthe ds medium. The brownian movement prevents or reduces sedimentation to a considerable ex ‘oom temperature by keeping the dispersed material in random motion. Effect of flocculation on sedimentation rate In a defloceulated suspension, the lager particles settle rela Particles. Asa resulta clear boundary between the sediment and the dispersion ‘easily distinguished and the supematent liquid remains cloudy for a considerable period ot However, in the ease of locculated suspension, groups of particles are agurevated nto Hoss foes tend to fall together while setting resulting in a clear bounda Ssupernatent liquid. The supernatent liquid in this ease is clear because even very sill pat present in the system are associated withthe floes and settle with it, Set sions dependson the size and porosity ofthe flocs but itis faster than dlefloeculated suspeasioes 62 depicts the sedimentation in floceulated and deflo ly ata faster rate than the sal dium sant between the sediment an ng in Mlocculated 5 culated suspensions Sedimentation Parameters ‘Two parameters namely sedimentation volume a inga formulation of suspension in terms of amount degree of sedimentation are usetil wie of foesCoarse Dispers Caw Dispersions 479, supernatant 100m Flocs @ my scasninsitatie) Terabe nspende, agcmentation volume vsgcinenttion volume i the ratio of ultimate volume ofthe sediment tothe total volume of th ees F=V/Y, er, F isthe sedimentation volume 1, iste ultimate volume of the sediment isthe otal volume of the suspension ‘The sedimentation volume (F) normally’ ranges from less than | to 1 and it may exceed! 1. For acole ifthe sedimentation volume is 0.70, it means that 70% ofthe total volume of the suspension sosupied bythe sediment. When F = 1, the sediment volume and the total volume are equal and suspension does not show any clear supernatent liquid on standing, Such suspension looks ‘excandis pharmaceutically acceptable. It i also possible forthe sedimentation volume to enseed ‘toa volume of the suspension de, fr F to become greater than | It indicates that the network ‘(es formed in the suspension is loose and fully and it encompasses a volume greater than the “inl solume of the suspension, ae of Flocculation Tse “etingnaton vol i fon in suspensions. The idea regarding the flocculation in suspens iifferent formulations in terms of fase (F) tothe sedimenta- BPE, sth cauad sediment volume because of culation ret deere of oesuation esto th ines Hn tune he cif) 2, the sediment volume in the Mocculated s0°P474 Physical Pharmacy 7 state. A suspension with & higher degree of flocculation i x94, i jocculated st sediment in the defloccul ferred. suspension of paracetamol in water, The initia Example 6.2 of the sediment was found to be 44 ml. Ifthe Determine the sediment: | i nl while th ie suspension was 100 m! w ftocelton ie 1.5, what i the defloceulated Volume volume of a2.5% WIV degree he final volume " ‘sedimentation volume? Solution Initial volume of the suspension (V,) = Final volume ofthe sediment (V,)=44 ml Degree of flocculation (B) = 1.5 100 mt Sedimentation volume, F= VJV,=44/100=0.44 Deflocculated sedimentation volume, F> FB oars = 029 FORMULATION OF SUSPENSIONS ‘Two approaches are generally followed in the preparation of physically stable suspensions, Th are: (i) The use of structured vehicle to maintain deflocculated particles. (i) The application of flocculation to produce flocs which though settle rapidly but are easyto redisperse, Structured vehicles prepared by the use of agents such as gums, sodium alginate, sodium carany methyl cellulose, ete. entrap the deflocculated particles and do not allow settling to take pl. Thisotropic behaviour of the suspending agent will be desirable as it will provide high consiseny ‘when the suspension is at rest and easy pourability when it is shaken. A disadvantage ofthis Proach in formulation of suspensions containing deflocculated particles is that some setling offi" cles eventually takes place which aggregate to form a cake. For this reason, formulation of susy recom: | mended. This enables the product to fl i in each dose, | pension as flocculated particles in structured vehicle is low easily from the container and a uniform dose is pou" Wetting of Particles This is generally powder in a vehile ma poe urine the formulation of suspensions. The dispersion and other contaminante Ta difficult due to adsorbed air at surface and minute quantities ia ints. The powder is not wetted and floats on the surface. He ofan ino 'Coarse agents such as polysorbate 80 or dioctyt soq FB Dispersions 476 wet ension between the solid particles and ¢h if which lower the contact angle between the; v hate to icles a hare leading to a deflocculated dispe 'ydrophobic pow derande® are generally pe substanees which help in wetting of insoluble ye thevehicleanda? anit ese hydrophilic substances flow into thew a “hes y 1, stan sand separate them, thus bringing about dispersio Fe trolled Flocculation ium sulfosuccin, " ate chicle. The oa Can help to reduce the in, sein ai IS 10 prevent formation of a compact sediment which is difficult to red ectrolytes act as Mlocculating agents by reducing the electric b Cult to redisperse cvienced by adecrease in the zeta potential and the formation of a brid i sto form a loosely connected floc. For example, bismuth tn ge between adjacent pari. se Meapasitive care or zeta potential, Because ofthe strong Tore of sae oet atta rales, he system is peptized or defloccuated and wil eventual rete na bees adj staasie potassium phosphate is added, the zta potential is decreased duet ne wa va sitive charge due to adsorption of the negatively charged phosphate ions. With the contin : sidition of electrolyt the zeta potential is reduced to zero, whereupon attraction forces brngabeat fenation of loose fTocs with a high sediment volume (Fig. 6.3). Ths is controlled flocculated faqersion which is stable and does not cake. tinuous addition of more electrolyte may bring about negative charge onthe bs- and low sedimentation volume results and eventual served with sulfamerazine dispersions (which are ier between the particles as cles 80 However, cont ruth subnitrate particles. Again repeptization ching may take place. Similar behaviour is o! ively charged) and when aluminium ions are used as electrolyte sed as wetting agents and sometimes bring Surfactants, both ionic and non-ionic have been u! :bout flocculation depending upon their concentration. Polymers are long chain, high molecular weight compounds co! its because a part of along their length. They act as flocculating agen! ntaining active groups spaced f the chain is adsorbed on the Adsorption —_ €) negative charge, Uncoated deliocoulated particles vet particles tation by charge neutralisation joccu Fig. 6.3. Controlled fParticle surface and the remaining past projects out ant the dispersion these loose parts leads to the formation of vcs. Hydrophilic polyme ‘oat the dispersed particles and act as protective coll ted Hi 1p ey such pis an ts Controlled Flocculation in Structured Vehicle teristies desired of a pharmaceutical suspension, thes sedimentation volume is not close towne. Hence, an ideal fi flocculation in a structured vehicle where the vehicle Would Fed ‘Thickening agents such as carboxymethyl cellulose, earbopol, vee ec. are generally added to form structured vehicles which slow doven the rate of sea 64), However, while formulating a ste tured vehicle, the change earied by the Moceulaing ap And the suspending agent must he hep in mind as it may cause incompatibility: Positively ean particles, flocculated with anionic electrolyte such as phosphate will be stabilized by uns ete, they ale have negat tna will he destabilized by positively carged gelatin. On the a hhand, negatively charged particles Mocculated with positively charged electrolyte AD wile compatible with gums. ech @) cave é ‘acsorbent @} ican LOY © © ©) wow, me GO (costvelyenarged ogatvelyenarged Seneuta panicles) Floceutate T panies | Suspenaing of agen SusponsenctVaceuated —Floceviated FI9. 64. Controlled flocculation in structured vehiclesideratior Cos cal COM ns arse Dispersions 477 considerations are important in pharm Pharmac ical 4 - eases which in turn affects the setting i Ce 2 Pr tributes als0 influence the flow aropeion nf erty peg en the product poured fom the bo the Jor ons wi : . preparations which are suspensions as they rey a in 'Y must spread !portant in the case | et Properly over the affe ao — - I over the affect aiff the pharmacetial suspension exhibit pas = nic properties. The rheolog depend oe ne te “aot Pt etn logical Properties depend on th; a artists lng aa he type ‘anh : ‘i hase ype and quantity of the suspending ahi ciate ‘ ° ; eat ig and thickening agent added to Fae preferred rheotowical behaviour fora pharmaceutical ogi ; la -al suspension is i sug nth isons: Te product ths hecomes hick on sanding. Th rosirden ty is prevents or reduces the Jed particles and eleg sof suspend 7 . sang of SUSPE nce of product improves. On shaking the product be vi pouring of the suspension from the bottle and hence dosing becomes es hi shen sit. Thinotropic fair athe privet ensires STOW recovery afer shaking otha th pariles inthe po 7 in the product fanremain suspended. lection of the rheological characteristics also improves the physical stability ofthe cettling, caking and particle growth can be avoided. Proper sel and problems li suspension EMULSIONS Anemulsion may be defined as a bi Jhasic system consisting of two im emulsic ig tic cispersed phase) is finely subdivided and yniformls Tispersed as dry rhecommous pltase), Since such a system is thermodynamicaly unstable, a suitable em agent is required to stabilize the miscible liquids one of which throughout the other ulsfying stem. from a mobile liquid 10 hase can range in consistency la .d systems range from lotions ‘and oral emulsions of re The dispersed phase or continuous pI hich are semi-solid in nature. The particle size ofthe semisolid, Thus pharmaceutical emulsifie iwely low viscosity to ointments and creams W Jipersed phase generally ranges from 0.1 10 100 Hm. TYPES OF EMULSIONS ‘-Oikin-Water Emulsions i a0 "amas sons on phases usualy er ici ge ; as in which oil is the dispersed oF discontinuous este esl fa is oil-in-water (o/w) emulsions. Such emulsions ed by emu mare enous “S¥sable taste and odour of the al generally masked ions a finely dispersed state gets asi) assim ls minis a ration should also be of of type- Olin NS |178 Physical Pharmacy rents since they provide a non-greasy use such as ereams, fotions and I product and ean easily be washed off from the skin. 2. Water-in-Oil Emulsions Water-in-oi (w/o) 1s are those in which oil forms the continuous oF extern; \ (wie) tsar th 1 ha water is the dispersed or discontinuous phase. Such emulsion are mostly used external ns. Such emulsions have an occlusive effect on the skin and are use for the il as cleansing creams since they solubilize thy si moisturising ereams. They are also rt form of w/o emulsions. These emulsions are however not always acceptable cosmetically pou at of their greasy feeling 3, Multiple Emulsions Inaddition tothe wo types of emulsions discussed above there are certain complex, multiple emus in shich the oil-in-water or water-in-oil emulsions are dispersed in another liquid medi, svaterin-il (oo) emulsion consists of very small droplets oF el dispersed in the water ick oil emulsion anda water-in-oil-in-water(w/o/w) emulsion consists of droplets se of an oil-in-water emulsion, More complex systems, such as waters insater iol involves two stages. For example, a w/o/w emulsion is prepared by first forming 2 water system and then dispersing this primary emulsion ina second aqueous phase. Multiple emulsion been proposed as potential candidates for sustained release dosage forms since the drug ent in the innermost phase has to pass through two other phases before being released for abs 4, Microemulsions ‘Normal emulsions generally contain globules ranging from 0.1 to 100 ym in diameter. Microema are emulsions that contain globules having diameters of less than 0.1 um, Droplets of such sions cannot refract light and, a a result, are invisible to the naked eye. Microemulsions thee appear as transparent solutions and are more acceptable physically in comparison to conven emulsions. Microcmulsions have been employed for preparation of both external as well asin formulations where they have exhibited better bioavailability than conventional emulsions IDENTIFICATION OF EMULSION SYSTEMS ‘A number of tests have been proposed to determine the type of emulsion. ‘one test should not be taken to be conelusive and the identity of an emulsion type shot! confirmed by atleast two test procedures. However, theresuls \salvays 4. Dilution Test The type of emulsion may be determined by diluting an emulsion w diluted with an aqueous solvent (e.2. milk, an 0 ino th ol or water. AO yw emulsion caf emulsion can be easilCoarse Ospersons 179 reas a water-in-oil emulsion can b am be di waer where esa arinlima ited with an ; Lig Adio ofthe sl : ani i ens “eta ’ petivity Test va onthe pint that an emulsion with an rabereas one with an oily coninousgheeteae Mimpand an electrical sources generally i ab een Wes. Condustivty tts, however may gv foeereei, give fle results “ waco ae ted tO tase Suapitofente in Ween with non-ionic sila cosio® oe oT Test sesoluble dye such as amaranth is mixed with an emulsion ast pitas willappen clare henuon io oyeueeghe vnc afte Simi, he coins ps ofa emu alsion would appear coloured by an ci-soluble dye suchas Sudan I “ sen 3 mesure Marea COMME vitesofao'w em ‘cobalt Chloride Test ter ape soaked ina cobalt chloride sou ermlsion, it indicates that the emulsion apse 0a sae eulsion is unstable or breaks in the presence of lectobes and allowed to dry tums from blue to pick on is of the ow type. This est however may not Fluorescence Test ons exposed to ulirvioletradisionand bseiednderamicnsons Tiyorescenve while an it-inate pe would tow ob Te have the eopet o exhibit uoescence on eNPOSE adkopofan emulsi ini emulsion should show continuous ‘pty Murescence. This is beeause many oi ‘ulaviolet ight ofthe emulsion spe ifthe ald noel 82 ons woud nol direction of Creaming Test ‘an emulsion can help are known than water. Ont inthe identification ‘water-in-oil emulsion tne ther hand, ow emul Tedirction of creaming 5 80 fests, tosis f the aqueous and oll phase Lsovasas iis generally ess nse am upwards, my ‘ARMACEUTICAL APPLICATIONS fr nisin oo nero and castor cilia pat emt 8 ae vile fem OF [EMULSIONS = or eps wing dress reid ori eso as 7 c sated into a siNe" . St emulsion, For example, oil 0 ‘8 formulation iain and C canbe forulbted ads to better absorption of vitamins4180 Physical Pharmacy som ne sed for stagnation seh 5X eam, outs adeninistration of oils and fe intrave arin Inlet ingest foe by oral route hig ‘extensively een used 10 prepare phate, ns.and lotions. i) Radtio-opngque em is) O'waypecmalsions wh (0) Fmulsioos ofboth os anal we spes Have preparations for externa use and (2) Emutsification by (vi) Deus which are susceptible to oxida fating them inthe form oFemnulsion.- (vin) Boa aiaily of evtainpoory soluble drugs can also be improved by dissolving them ig andemulsifying cosmetic as also ben sedi aero PH jon or hydrolysis ean sometimes be stabilized by, THEORIES OF EMULSIFICATION When one liquid is broken into small particles, the interfacial area of the globules consis aoe ctnaticenormos compared withthe surface area of the original liquid. There an eno arcaaein few energy associated with the large increase in surface area ofthe oil and hence tocomesthermodynamically unstable and separates into two phases due to coalescence of oi let, In order to stabilize the emulsion, emulsifying agents are added. These act by reducing interfacial tension between the two phases and forming a stable interfacial film between thet ‘The siabilty ofa prepared emulsion is primarily determined by the strength and nature ofthe int file formed. ‘An ideal emulsifying agent for pharmaceutical use shouldbe stable, inert and free fom ois: inten properties. should preferably be odouress tasteless, colourless and should produce su ‘emulsions ofthe desired type at very low concentrations. Enmulsfy ing agents ean be broadly classified into three groups (Surfactants whieh get adsorbed atthe ‘and thereby reduce interfacial tension, (ii) Hydrophilic colloids which form a multimolecular film around the dispersed droplesf inanoil in water emulsion, (ii) Finely divided solids which get adsorbed at the interface between the wo iis liquid phases and forma film of particles around the dispersed globules. ater interface to form monomolecular i |, Monomolecular Adsorption Surfactants are substances containing both hydrophilic an ie regions in eirmsec = ie Ths ying ore thers sachs te HSB lar groups ae oriented towards ol while the hydrophilic polar groups ate oriented WA Sater hs forming be i, This Hasse are cals SE es ofthe dispersed phase good emulsilying agent also reduces the intertiia tense0Coarse Dispersions 184 ses thesrftse free ences and hence the eg atblity is the presence of sunt charg ers Te presence of charges on the sua ch lobule. Overlapping ofthese ancy aoe Waals forces of atraction of emulsion produced ie, whether ot The PE » whether of or wio depends i eIHL ef emulsifier For enna; Woe ae ego ein apie range of 910 12 whereas masons ar ome ene Ht ofthe mas U2 ln An line Sx repton ence ges tbliscrnesenceane net MerEhet rico arephi wien ee ohons From practical point of vi ‘evioil phase give stable emulsions Thetpe of emulsion formed isa func shichthe emulsifier is more soluble hecomes th rah As mentioned above, Teens with hi fat of an ohv er can, { Matimotecular Adsorption dropilc colloids gene Igenser film are ly act by formin strong and resist coales 'g nultimolecular layers at the interface, The formed nce. They donot cause appreciable lowering of itera ‘stewin. An alditonal effect of these hydrocolloids isthe significant incre the viscosity of| Sesion which in turn decreases coalescence Since they are hydepilethy Promote only o/w Peemulsions. Their use is limite large numberof synthetic sufactans, Teatstaial strength of ye barir is increased by adding gelatin which stem etten iso anionic hydrocolloids suchas carboxy methylcellulose, gelation isinduced at low ‘Mlansthe film formed is rigid "Solid Panicies Adsorption {Seis did stds having suitably balanced hyophilc and lipoptite properties havea divided solids having suitably balanced hydrop SOE ASunabteahe over eras olds oer nee fi at reve SSE ofthe dispersed globules. the sli parle re Ieee wt aw/ so St*Sshs while preferential wetting by water rest inthe formation of emulsions ancl while preferential wetting b fra, sill clays and several inorganic substancesare effective emulsfjingagens when in A dda sae, PSIcaL STABILITY OF EMULSIONS lag *Pulsion is characterize by the absence tender fs omc ies #4 maintenange of elegance with respest © APPERIRCE. = i sion can beclasified as follows mata causes of instability in pharmaceutical emulsion can be182 Physical Pharmacy 1. Flocculaton and Creaming. 2. Coaescence and breaking 3. Physical and chemical changes 4, Phase inversion eoulat ami , 1, Floceulaion and Cre a ay secumtation of oles oF he diapered ey reaming isa phenomenon character pel i tearing use Theat of reaming is o¥er8 PY ve ish, where, + isthe teminal velocity nome, : 4 loth diameter ofthe patcles of dispersed phase in em, 1; isthe density ofthe dispersion medium, 2 isthe acceleration due to gravity and 1, isthe viscosity ofthe dispersion medium in poise Upward creaming generally result in of emulsions when the density ofthe dispersed phase less than that ofthe dispersion medium. Downward creaming (or settling) generally result ia wt ‘emulsions where the density of the dispersed phase is more than the dispersion medium. reaming sa reversible phenomenon and except for inelegance and unequal distribution of iférugistaken without shaking, it isnot such a serious problem. Rate of creaming can be dec ty: (i) Increasing te viscosity ofthe dispersion medium by the addition of viscosity improven thickening ayents such as methylcellulose, tragacanth, sodium alginate, gelatine. (i) Reducing the panicle size ofthe globules of the dispersed phase by homogenisatin. (i) Minimizing the difference in the density ofthe two phases. This is however difficult the density changes with temperature and agents requited to increase the dens ft oilphase such asa-bromonaphthali ; intra use tomonaphihalein bromoform, carbon tetrachloride, et are OveCoarse Oispersons 103 ai i ameter to pase (0)=8 uma 194 eT ese as (P= 092 ps epson median (2) LO pe persion edi (7) = 12 pie et gut riy() = 981 ee! __ 81047 (0921.08) «981 1ee12 64 10-8 (0.16) «981 216 = 465» 10emise. ayhas 24 ~ 60 60 = R600 see,the rate oF upward creaming Ly = 4.65» 10-®ersee #6400 seelday 40 crnday sevea 1. coalescence and Breaking Covkscenoe i characterized by the merging or agutegation of plabulesf the sere pase and rounding dispersed globules. TBS teal occurs de tothe rupture ofthe intefaca) sree Gc phenomenen as the coatescance of he apes PSS ress inthe rcakig WP oF ‘mln and itanmot be reformed easily Fests whieh can reduce the chances of reskin 6 {0 Uniformity of particle sie of dispersed Phase: Gi) irene nae viscosity ofthe emulsion toa PUT eve sin tion and coalescence. Ui) Phase volume ratio: The dispersed Ps lobules may coalesce and the emulsion likely to give most stable emulsions we thishinders occu fess than 74965 ould be | rae le 1 és a“ nay break A phase ¥ of 50/50 is phy Vysical and Chemical Changes jount sontain excessive a Ya ral pus, sa : Mal ems, starches, ee, used as mull may conta own ol ctl rsh may cause ean it pando comparatively more stable184 Physical Pharmacy ies, ete, carry electric charges. Neur 1kdown of the emulsion. Some emulsifiers such as soaps, a ast charge by an added substance may eause brea ti tg 4. Phase inversions “An ow emalsion prepare with sodium stearate (monovalent Soap) an be inverse yg ty adding calcium chloride to form calcium stearate (divalent soap) Thiet nay also be produced by alterations in phase wolUme rato. For exams and afte quantity of water, a w/o emulsion is produced py 28° orms wo emulsion, But when more water is added sc, nein is produced. Inversion has also been observed wher Pe sating and mixing the Wwo phases, is cooled. fie qn solubility of the emulsifying agents. Phase inversion ey 1d 74% of total volume of the emulsion, the ted emulsifier is mixed Since water volume inversion occurs and an olWw sion, which has been prepared by temperature dependent changes vented by choosing proper emulsifying agents in better to ensure the internal phase does not exceet less, ei Assessment of Stability of Emulsions mulsions ean be assessed by observing the rate of separation ofthe disperse phsseyg smining the degree of creaming. This methodis suiablcay study, the rate of cei Stability of distinct layer from emulsion i. by deter for unstable emulsions that exhibit creaming quickly. For acceler may be inereased by centrifugation A precise assessment of the phy ysical stability can be made by studying the changes in sie ‘with ime. Measurement of globule size can be underaer intervals. The changes in the shape ofthe curve shown indicate unsaiy carried outat different time more reliable resutean Stability can be assessed in terms ofrateat which such changes oceur, A culating changes in the number of globules per millimetre Other methods such as Coulter counting, turbidimetric analysis and ter been used to evaluate new emulsifying agents and to determine the stability of emulsion perature tests havea PRESERVATION OF EMULSIONS 4. Preservation from Micro-organisms Presenatio of emulsion from micro-organisms is necessary since these ean poi emulsified systems with a high water content, particularly if earbohydrates, proteins oF sei tnaterials are also present, Microbial contamination can result in problems such 28 200%" change. yas production, hydrolysis, pH change and eventually breaking of emulsion. E¢0! te no sisible physical changes due 10 microbial contamination, the preparation wil auiministration, Hence it is necessary that emulsified systems be adequately prese™"Coarse Dispersions 185 sn desirable properties of an efficient preservative for emul ied systems include the ideal preservative should be non-irritant, it i) anise non-sensitizing and non-toxic i (0 gn used. 1 and non-toxic in the concen- an Id be physically as well as chemi ible wit cy Hat dh the posed conaiesonne een eae ofthe «apt should not impart any taste, colour or odour to the produc : (ny Htshould be stable and effective over a wide range of pH and temperature (n) Itshould have a wide spectrum of activity against a range of bacteria, yeast and moulds. (ui The selected preservative should have a high water solubility and low oiliwater partition coefficient {ui ltshould have bactericidal rather than bacteriostatic activity. (ui) Itshould be rapidly effective even in the presence of large microbial load. Examples of antimicrobial preservatives used to preserve emulsified systems include paahydroxybenzoate esters such as methyl, propyl and butyl parabens, organic acids such as sorbic vedand benzoic acid, organic mercurials such as phenylmercuric acetate and phenylmercuric ni tae quaternary ammonium compounds such as cetrimide, cresol derivatives such as chlorocresol ilniscellaneous agents such as sodium benzoate, chloroform and phenoxyethanol Since it is the unionized state of the preservative which is able to penetrate the bacterial cell renbranes, hence the pH should be low for weakly acidic preservatives such as benzoic acid and rixture of methyl and propyl parabens. Factors which can reduce the preservative activity are binding or complexation of the preserva tne wih one of the components of emulsion and adsorption of the preservative by the container chose ce, so that the concentration reduces below the minimum inhibitory concentration, Hence, thse interactions should be taken care-of while selecting a suitable preservative. 2 Preservation from Oxidation May vegetable and mineral oils and animal fats present in emulsified systems susceptible to Ove changes such as raneidity and spoilage due to atmospheric oxygen and effects of enzymes Podused by micro-organisms, Changes due to atmospheric oxygen can be effectively prevented by i eofsuitable antioxidants i.e. agents Having. high affinity for oxygen and compte Forti alps tbsances in the formulation, The ideal antioxidant should be nono tno 7 Je, ventration under the expected conditions of storage and use, soluble inthe med i ‘eaetions other than oxidation). Antioxidant for use in oral preparayions ee te utp it tsteless. Some of the commonly weed ntioxidants for emule spc Hoon such as ethyl, propyl or dodecy! gallate, butylated hydroxyanisol . ene (BHT) and tocopherols186 Physica! Pharmacy Rheological Considerations ‘Mut ofthe emulsion ystems encountered in the Feld of pharmacy such as lotions ang non neatonunercept fora ver fe dilute ones (eomaining upto 20°» ofthe dispersed pa ee ea eee eee ge hand emulsions such as fotions containing about 3g eS while those approaching semrso dispersed phase generally exhibit pseudoplastc behaviout Nae rom $0 to 73% of dispersed Phase are plastic such as cosmetic ereams containing ang rarked yield values The semi-clid creams are usualls viscoelastic Dilferent shevlogcat gyn can be conferred on these emulsion by merely varying the concentration of the dispersed gh. the nature and concentration of the emulsifying agent 1 of the consumer, shear-thinning emulsions are particularly hunt of view of the ci she PARICHIATS pete, rable gonststensy oF bey When removed from the pe raetrpe lotoas exhibit consulerablecoasteme sy th bottle shaken, they hoose the consistency ante From the ps as creams. Thus, they have a consider spread easily on application to the skin. T allowed to stand at rest the bottle Once tl pour from the bottle Proper theological characteristics als confer stability om the emulsified systems and poy Tike creaming, coalescence and breaking ar avonled Release of drugs from the emulsified may also depend on thet rheological characteristics REVISION EXERCISES Long answer type questions: 1 Write an account of emulsions under the following headings a) Define b) Emulsion type ©) Pharmaceutical applications 4) Emalsifying agents €) Bancroft’s ule Discuss pharmaceutical suspensions under the following headings. 3) Definition by Interfactal properties of suspended particles €} Pharmaceutical applications 2) Formulation of suspensions 3. Describe the controlled flocculation in structured vehicle approach forthe 2 stable suspension, What isthe importance of wetting of particles? 4 Discuss the factors that lead to instability of pharmaceutical ‘emulsions and bo™: overcome or minimize these problems $. Discus he concep of structured vehicles inthe formulation of suspensions examples