Phardose Report Final

7/24/2019 Phardose Report Final

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Disperse System -The term "Disperse System" refers to a system in which one substance (The Disdistributed, in discrete units, throughout a second substance (the continuous Pha as- ach phase can e#ist in soid, i$uid, or gaseous state! - The partices of the dispersed phase vary in si%e, from arge partices visibe to to partices of cooida dimension, ranging between '! nanometer and ! micro*The term "partice" shoud not be confused with "moecue"! The moecue is theof any chemica compound that possesses a the native properties of that compoconcise of numerous moecues, generay in soid state (but can be i$uid or gase - Dispersions containing course partices usuay ' to micrometer, are caed

dispersions ( suspensions and emusions )! Dispersions containing of smaer si%edispersion (!-' micrometer) such as agmas and ges and, if the partices arerange, cooida dispersions!

Partices in a coarse dispersion have a greater tendency to separate from the dismedium than do the partices of +nes dispersions, mainy because of their greatesoids in dispersion tend to sette at the bottom of the container because of theirthan the dispersion medium!

ompete and uniform redistribution of the dispersed phase is essentia to the ac



SUSPENSIONS-Suspensions are preparations containing +ney divided drug partices (the suspenssomewhat uniformy throughout a vehice in which the drug e#hibits a minimum desoubiity! .eneray, this type of product is a powder mi#ture containing the drug asuspending and dispersing agents to be diuted nag agitated with a speci+ed $uanmost often puri+ed water!-Prepared suspensions not re$uiring reconstitution at the time of dispensing are simas "/ra Suspension" Reasons fo Suspension - ertain drugs are chemicay unstabe in soution but stabe when suspended!- 0or many patients the i$uid form is preferred than the soid form of the same druis easier to swaow and the 1e#ibiity in administration of a range of doses! This is advantageous for infants, chidren, and the edery!-The disadvantage of a disagreeabe taste of certain drugs in soution form is overcdrug is administered as undissoved partices of an ora suspension!- /ra suspensions are a$ueous preparations with the vehice 1avored and sweete

anticipated taste preferences of the intended patient!

Features Desired in a Pharmaceutical Suspension2n addition to therapeutic e3cacy, chemica stabiity of the components of the formpermanency of the preparation, and aesthetic appea of the preparation, desirabe

pharmaceutica preparations, a few other features appy more speci+cay to the phsuspension4



Sedimentation Rate of the Particles of a Suspension The various factors invoved in the rate of setting of the partices of a suspension are$uation of Sto&es 8aw! The Sto&es e$uation was derived for an idea situation in which uniform, perfecty spvery diute suspension sette without producing turbuence , suspensoid, and withou

physica attraction or a3nity for the suspension! /bviousy, the Sto&es e$uation doepharmaceutica suspension!9owever, the basic concepts of the e$uation do give a vaid indication of the factorsto suspension of partices and a cue to the possibe ad:ustments that can be made tdecrease the rate of sedimentation! ;educing the partice si%e of the dispersed phase produces a sower rate of descent 5so,the greater that density of the partices, the greater the rate of descent, provid

vehice is not atered!

2f the partices are ess dense than the vehice, they woud tend to 1oat! The rate of sedimentation may be appreciaby reduced by increasing the viscosity omedium, and within imits of practicaity,this may be done! 9owever! a product haviviscosity is not generay desirabe because it pours with di3cuty and it is di3cut tsuspension!

The viscosit of the harmaceutica re aration ma be determined throu h the use



Physical Features of the Dispersed Phase of a Suspension .eneray, partice si%e reduction is accompished by dry miing prior to incorporatiophase into the dispersion medium !

/ne of the most rapid, convenient, and ine#pensive methods of producing fine drug

si%e is micropulverization! icropuveri%ers are high speed attrition or impact mireducing powders to the si%e acceptabe for most ora and topica suspensions! 0or sti finer partices, under ' >m, uid enery rindin, sometimes refered to microni%ing, is $uite e?ective! <y this process, the shearing action of high-veocity cairstreams on the partices in a con+ned space produces the desired utra+ne or micpartices to be microni%ed are swept into vioent turbuence by the sonic and supersairstreams! The partices are acceerated to high veocities and coide with one anot

fragmentation! This method may be empoyed when the partices are intended for popthamic suspensions!

Partices of e#tremey sma dimensions may aso be produced by spray dryin! 5 sshaped apparatus into which a soution of a drug is sprayed rapidy dried by a currecircuating in the cone! The resuting dry powder is coected!wea& 2t is not possibe for a pharmacist to achieve the same degree of partice si%e reduc

comminuting e$uipment as the mortar and peste!



The reduction in partice si%e produces sow, more uniform rates of setting! 9owevereducing the partice si%e too much because +ne partices have tendency to form a csetting to the bottom of the container!

The partice shape of the suspensoid can aso a?ect ca&ing and product stabiity! Thpartices formed a tenacious sediment ca&e on standing that coud not be redistribu

barre-shaped partices dis not ca&e upon standing!/ne common method of preventing ridged cohesion of sma partices of a suspensioformation of ess rigid or oose aggregation of the partices hed together by comparto-partice bonds!

0oc or 1occue a common method of preventing rigid cohesion of sma partices ofintentiona formation of a ess rigid or oose aggregation of partices!

-The 1ocs sette to form a higher sediment voume than un1occuated partices, the which permits the aggregates to brea&-up easiy and distribute readiy with a sma a Electrolytes can aso act as 1occuating agents, apparenty by reducing the eectricthe partices of the suspenoid and forming a bridge so as to in& them together!

Nonionic and ionic surface"active aents (surfactants) can aso induce 1occuat

suspension and increase the sedimentation voume!



Dispersion #edium @hen highy 1occuated suspensions sette too rapidy, they produce an unsighty s 2n many commercia suspensions, many suspending agents are added to the disperit structure! arbo#ymethyceuose (), ethyceuose, microcrystaine ceuospoivinypyrroidone, #anthan gum and bentonite are among a few of the agents usedispersion medium! @hen poymeric substances and hydrophiic cooids are used asappropriate tests must be performed to show that the agent does not interfere with

drug! The amount of the suspending agent must not be such to render the suspension toodistribute the suspensoid)or to pour! The study of the 1ow characteristics is termed Preparation of Suspension 5coho, gycerine, propyene gyco, and other hygroscopic i$uids are empoyed as a$ueous vehices are to be used as dispersion phases! They function by dispacing tof the partices, and aowing penetration of dispersion medium into the powder! o

scae preparations, wetting agents are mi#ed with the partices by an apparatus sucscae in the pharmacy, they are mi#ed with a mortar and a peste! @henever appropriate, suitabe preservatives shoud be incuded in the formuationpreserve against bacteria and mod contamination!

Sustained"Release Suspensions The formuation of i$uid ora suspensions having sustained-reease has had ony imof the di3cuty of maintaining the stabiity of sustained-reease!

Product deveopment research has centered on the same types of technoogies usesustained reease tabets and ca sues coated beads dru -im re nated wa# matri#



E&temporaneous compoundin of Suspensions

• Drugs in i$uid form have faster decomposition rates than in soid form and somthe p9 of the medium!

• 8eucovorin cacium when compounded from crushed tabets or the in:ectabstabe in mi& or antacid and is unstabe in acidic soutions!

• Prednisone ora suspension and &etocona%oe suspension = e#temporaneous foappeared in the professiona iterature

• ;ifadin (rifampis, 5ventis) - provide in the pac&age insert a formua for preparai$uid form

• Typicay, in formation of an e#temporaneous suspension, the contents of a capinto a mortar and peste!

• A vehice B paste and then diuted to the desired voume

• Seected vehice = can be a commercia product, such as the /ra famiy of prepSweet, /ra-sweet S0, /ra-Pus, /ra-<end, Paddoc& 8ab!)

• Some suspensions shoud not incude preservatives, coorings, 1avorings, or apotentia for each of these to cause either acute or ong-term adverse e?ects!

• #! 8i$uid suspension of neonate

• administered through a tube threaded through the mouth into the stomtaste is usua underdeveo ed, a 1avorin a ent is not re uired



• Cehices such as 5romatic i#ir, 0, contain a signi+cant amount ofacoho, 6'-67E, which are not suitabe for use

• 'enzyl alcohol - can cause a gasping syndrome characteri%ed by adeterioration of mutipe organ systems and eventuay death!

• Propylene lycol = can cause probems such as sei%ures and stupor insome preterm infants

• Shoud be paced in air-tight, ight resistant containers and stored in therefrigerator!

• The patient shoud be instructed to sha&e it we and watch for any coor changconsistency change that might indicate a stabiity probem!

Pac$ain and Storae of Suspensions

containers having4

'! 5de$uate airspace above the i$uid (permit ade$uate sha&ing)

6! wide mouth containers (permit prompt and ease of remova of suspension)

7! tight containers protected from free%ing, e#cessive heat and ight!

2t is important that suspensions be sha&en before each use to ensure uniform

E&temporaneous compoundin of Suspensions



E&amples of Oral Suspensions and theirrepresentative commercial products (y )ateory*

+! ,ntacids

a) 5umina, agnesia and Simethicone - yanta i$uid

b) agadrate /ra Suspension - ;iopan /ra Suspension

c) agnesia and 5umina /ra - aao# Suspension

d) 5uminum 9ydro#ide and agnesium arbonate - .avisconi$uid

-! ,nthelminitics

e) Pyrante Pamoate - 5ntiminth /ra Suspension

f) Thiaben%adoe /ra Suspension - inte%o /ra Suspension

.! ,nti(acterial /,nti(iotics0

g) horamphenico Pamitate - horomycetin Pamitae /raSuspen!

h) rtythromycin stoate - 2osone /ra Suspension

1! ,nti(acterial /non"anti(iotic ,nti"infectives0

i) ethenamine andeate - andeamine SuspensionF0orte

:) Sufametho#a%oe and Trimethoprim - <actrim, SeptraSuspension

&) Sufametho#a%oe - .antano Suspension

) Su+so#a%oe 5cety /ra Suspension- .antrisin SyrupFPedia

2! ,nticonvulsants

m) Pimidone /ra Suspension - ysoine Suspension

3! ,ntidiarrheal

a) <ismuth Subsaicyate -

4! ,ntiatulent

a) Simethicone /ra Suspe5! ,ntifunals

b) ystatin /ra SuspensioSuspension

c) .riseofuvin /ra SuspenSuspension

6! ,ntihypertensive

d) ethydopa /ra SuspenSuspension

+7! ,ntipsychotics% Sedative

e) 9ydro#y%ine Pamoate /Cistari /ra Suspension

f) Thiorida%ine /ra SuspeSuspension

++! Diureticg) horothia%ide /ra Susp



,ntacid Oral Suspension

• counteract the e?ects of gastric hyperacidity (peptic ucer patients)H soothe the irritatedinings of the .2T

• reduce the eve of acidity in the stomach

• widey empoyed and sod /T to patients with acid indigestion, and heartburn

• composed of water insoube materias

• E&amples* Sodium <icarbonate, 5uminum hydro#ide, 5uminum phosphate,Dihydro#yauminum aminoacetate, acium carbonate, acium phosphate, agadagnesium carbonate, agnesium o#ide and agnesium hydro#ide!

• Sodium <icarbonate, acium arbonate, and agnesium 9ydro#ide = neutraie?ectivey!

• agnesium trisiicate and auminum hydro#ide = neutrai%e gastric ess e?ectiv

more sowy!• @hen seecting an antacid4

• adverse e?ects of each agent in reation to the individua patient

• #ampes4

• Sodium (icar(onate - sodium overoad and systemic a&aosis

• #anesium - ead to diarrhea

• )alcium car(onate - induce hypercacemia and stimuation of gastric se

acid production• aluminum hydro&ide - ead to constipation and depetion with constant



• 8i$uid suspensions assert more immediate reaction and do not re8uire timdisinterate!

• 0D5 re$uires that antacid not intended to be chewed must disintegrate within 'because endoscopic studies have shown that very itte antacid remains in the fhour after administration!

• food snac&s - proong the action of the antacid

• 8i$uid antacid preparations4• are peasanty 1avored (usuay with peppermint) - enhance their paatabiit

appea• contain a arge amount of soid materia• sha&en vigorousy

,nti(acterial Oral Suspension

• The antibacteria ora suspensions incude preparations of antibiotic substances

Examples: ,nti(iotics /horamphenico pamitate, rythromycin derivatives, aand its derivatives0% Sulfonamides /Sufametho#a%oe, su+so#a%oe acety0% othinfective aents /methanamine mandeate and nitrofurantoin0% com(ination o/sufametho#a%oe - trimethoprim0

• any antibiotic materias are unstabe when maintained in soution for an appre

,ntacid Oral Suspension



• Dispersing phase = a$ueous and usuay coored, sweetened, and 1avored to remore appeaing and paatabe!

• #! Pamitate form of choramphenico = water insoube and 1avoress

Rectal Suspensions

Examples: 'arium sulfate for Suspension, ISP - oray or rectay for the diagn

visuai%ation of the .2T• #esalamine /2"aminosalicylic acid0 = introduced as ;owasa (5aven)H for tre

rohnJs disease, dista ucerative coitis, proctosigmoiditis, and proctitis!

• )olocort /Paddoc$ 9a(0

• treatment of ucerative coitis• pac&aged in a convenient disposabe singe-dose enema designed for sef-a

Dry Po:ders for Oral Suspension • Preparations consist of dry powder mi#tures or granues• The dry products contain4

5ntibiotic , oorant (0D and dyes) , 0avorants , Sweeteners - sucrose or sodiumStabii%ing agents - citric acid and sodium citrate, Suspending agents - guar gum,methyceuose , Preserving agents - methyparaben, sodium ben%oate

/T4 ";/ST2TITK and dispense - oosen the powder at the bottom of the cothen add abe designated amount of puri+ed water, and sha&e we unti a of the

been suspended!



#ampes of 5ntibiotics for /ra Suspension(;econstitution)4

• 5mo#iciin for /ra Suspension 5/L28

• 5mpiciin for /ra Suspension /2P

• <acampiciin for /ra SuspensionSPT;/<2D

• efacor for /ra Suspension 8/;

• e+#ime for /ra Suspension SIP;5LP/@D;

• ephadrine for /ra Suspension G08L

• Dico#aciin Sodium for /ra Suspension(P5T9/28)

•

Do#ycycine for /ra Suspension C2<;5M2//9MD;5T

• puri+ed water rather than tap water is needed to avoid the possibiity of adding

• Stored in sighty oversi%ed container to permit ade$uate sha&ing!

• 0imaster or 0imaster Pus are devices avaiabe to aid in accurate reconstituti

/ther e#ampes (ombination)4 '! rythromycin ethysuccinate an

acetysu+so#a%oe granues for oracute midde ear infection (9emopin1uen%ae)6! Probenecid and ampiciin for retreatment for uncompicated infecendocervica or recta)H (eisseria

/ther drugs for reconstituton4• hoestyramine (Nuestran, Par)

of hyperipidemia• <arium sufate (<arosperse, a

o radiopa$ue contrast mediu.2T

o To diagnose conditions of thesophagus, stomach, smacoon

o 5vaiabe as a bu& powder



E#U9SIONS

• from emugio (to mi& out)

• a dispersion where the dispersed phase (sma gobues of a i$uid) is distributedthroughout a vehice in which it is immiscibe!

Emulsion terminoloy

•

dispersed phase - Internal phase• dispersion medium = External/Continuous phase

Types of Emulsion:

• oil-in-water (o/w) emusions• oeaginous interna phase O a$ueous e#terna phase• may be diuted or e#tended with water or an a$ueous preparation

• water-in- oil (w/o) emusions• a$ueous interna phase and an oeaginous e#terna phase• may be diuted with an oeaginous or oi-miscibe i$uid

• emulsifying agent - 7rd phase is necessary to prepare a stabe emusion• absence of emusi+er4 dispersion is unstabeH gobues undergo coaescence

ayers of water and oi)

• Pharmaceutica emusions may be prepared as i$uids and semisoids!

• 8i$uid emusions = may be empoyed topicay, oray, or parenteray• =



Purpose of Emulsi;cation

• Pharmaceutically

• prepare a stabe and homogenous mi#ture of 6 immiscibe i$uids

• 2t permits administration of i$uid drug in minute gobues form rathbu&!

• <herapeutically

• for rate and degree of absorption of the drug• /F@ type = for paatabe administration of distastefu oi by dispersin

sweetened, 1avored vehice!• reduced partice si%e of oi gobues - more digestibe and readiy ab

more e?ective (e#! 2ncreased e3cacy of minera oi as a cathartic wemusi+ed)

• appied e#ternay - medicina agent irritating to the s&in surface incthe interna phase (in direct contact with the s&in)

• @F/ emusion - appied more eveny on the un(ro$en s$in

• S&in is covered with a thin +m sebum, more readiy wetted by o



• Surface <ension <heory

• e#posed surface of i$uids tends to contract• interna forces in a i$uid drop promote the association of the moecue of

substance resisting distortion of the drop into a ess spherica form!

• emulsi;ers and sta(ilizers lo:er the interfacial tension /surfaceactive/surfactants/or wetting agents) of the - immisci(le li8uids% reducin the repellant force (et:een the li8uids diminishin eachattraction for its o:n molecules

• Oriented":ede <heory

• certain emusifying agents orient themseves about and within a i$uid actheir soubiity in that i$uid!

• emusifying agent with greater hydrophiic character promotes an /Fw ememusion through use of more hydrophobic emusi+ers!

• Plastic or Interfacial"Film <heory

• emusifying agent (at the interface between the oi and water), surroundsof the interna phase as a thin layer of ;lm adsorbed on the surface of t

• +m4 prevents the contact and the coaescence of the dispersed phase,• the tougher and more piabe the +m, the greater stabiity of the emusio

<heories of Emulsi;cation



Emulsi;ers and sta(ilizers for pharmaceutical systems*arbohydrate materias

5cacia- used in the preparation of e#temporaneous emusions Tragacanth- thic&ening agents in acacia-emusi+ed products5gar- thic&ening agents in acacia-emusi+ed productshondrusPectin

icrocrystaine ceuose- used in suspensions and emusions as a viscosity reprovide dispersion stabiity

They form hydrophiic cooids which when added with water produce oFw emusio Protein substances#! .eatin, gg, Mo&, aseinDisadvantage of geatin4 the emusion is too 1uid and becomes more 1uid upon st These substances produce oFw emusions 9igh moecuar weight acohos#! Steary acoho, ety acoho, .ycery monostearate

Ised as thic&ening agents and stabii%ers for oFw emusion#! hoesteroF choestero derivatives

Ised in e#terna emusion to promote wFo emusions



p? rane

,nionic Q

)ationic 7-R

Nonionic 7-'

•@etting agents'!5nionic- negativey charged

•onovaent, poyvaent, organic soaps#! Triethanoamine oeate, Sufonates (sodium aury sufate)

'!ationic- positivey charged#! <en%a&onium choride (bactericida properties)

6!onionic- show no incination to ioni%e#! Sorbitan esters, Poyo#yethyene derivatives• These agents contain both hydrophiic and ipophiic groups•8ipophiic protein- for the surface activity of the moecue•5nionic and cationic neutrai%e each other and are considered incompatibe ?ectiveness4

•0iney divided soids'!ooida cays

#! <entonite, agnesium hydro#ide, 5uminum hydro#ide•2nsoube materia A 5$ueous phase (greater voume) oFw emusions•Powdered soid A /i (greater voume) wFo emusion#! <entonite• The reative voume of interna and e#terna phases depends on the type of emusi+er used•2nterna concentration and viscosity of an emusion are inversey proportiona•musions may be prepared without inversion with as much as about RE of the voume of the interna phase

<he ?9' System



y9ydrophiic-ipophiic baance #ethods of Emulsion PreparationSma scae#! Dry wedgwood, porceain mortar and peste, mechanica bender or mi#er (@arinmi&sha&e mi#er), hand homogeni%er, bench-type homogeni%er, simpe prescription

8arge scae#! 8arge mi#ing tan&s (high speed impeer), cooid mi, industria homogeni%ers The products are +ner by passage through a cooida mi2ndustria homogeni%ers have the capacity to hande ', 8 of productF hour Sma-scae e#temporaneous preparation ontinenta or dry gum method

The emusifying agent (usuay acacia) is mi#ed with oi before the addition of water464' method parts of oi, 6 parts of water, ' part of gum

Ex ! 5cacia or other oFw emusi+er is triturated with the oi in a dry wedgwood or porpeste unti thoroughy mi#ed (rough surface mortar is preferred to ensure proper grof gobue si%e)! 5fter the oi is mi#ed with the gum, the water is added immediateyemusion is creamy white and produces a crac&ing sound! 5ppro#imatey 7 minutesre$uired! Soid substances ( preservatives, stabii%ers, coorants) are dissoved in a s

before adding to the emusion! 5ny substances that might interfere with the stabiityshoud be added ast!



ngish or wet gum method The emusifying agents is add to the water to form a muciage, and then the oi is sform an emusion The same proportions are used but the order of mi#ing di?erent and the proportion vary <otte or forbes botte method This method is used for voatie ois or ess viscous ois2t is a variation of the dry gum methodot suited for viscous ois because they cannot be thoroughy agitated in the botte the emusifying agentDry gum method is used when the intended dispersed phase is a mi#ture of +#ed oiEx. Powdered acacia is paced in a dry botte, 6 parts of oi are added in proportions thoroughy sha&en! 5fter a the water has been added, the primary emusion may b

proper voume with water or an a$ueous soution! 5u#iiary method5n emusion prepared by wet or dry gum method can increase in $uaity using a han The pumping action of the hande forces the emusion through a very sma ori+ce reof the interna phase about mcm or ess9and homogeni%er is ess e3cient in reducing the partice si%e pf very thic& emusioempoyed for emusions containing a high proportion of soid matter

2n Situ soa method

acium soaps



acium soapswFo emusionontained vegetabe ois such as oeic acid, that is combined with imewatermusifying agent4 cacium sat of the free fatty acidWhen olive oil is used

musifying agent4 cacium oeate0ree fatty acid4 oeic acid

Di3cuty when preparing sef-emusifying product4 the amount of free fatty acid on tinsu3cient in a '4' basis with cacium hydro#ide, thus, addition of oive oi or oeic a/therwise, tiny dropets of water form on the surface! #terna phase4 oiH idea where s&in softening and occusion are desired (itchy, dry Ex. aamine iniment

icroemusions

Thermodynamicay stabe, opticay transparent isotropic mi#tures of a biphasic oFwwith surfactantsDiameter of dropets4 'U to ',U (macromoecues4 ,U)<oth oFw O wFo microemusions may be formed The type of emusion produced depends on the properties of the oi and surfactants 9ydrophiic surfactantsProduce transparent oFw emusion98< range of the surfactant4 '-'Q



2f the aggregates are di3cuty to disassembe or if insu3cient sha&ing, improper dos



gg g y g p presutot estheticay acceptabe2t increases the ris& that the gobues wi coaesce 5ccording to Sto&es $uationX The rate of separation of the dispersed phase of an emusion may be reated to suchpartice si%e of the dispersed phase! The rate of separation is increased by increasedthe interna phase! The di?erence in density between the phases! 8arger density di?erence between tw The viscosity of the e#terna phase! Decreased viscosity of the e#terna phase!

To increase the stabiity of an emusionX The gobue or partice si%e shoud be reduced as +ne as is practicay possibe The density di?erence between the interna and e#terna phases shoud be minima

Ciscosity of the e#terna phase shoud be reasonaby high Thic&enersEx. Tragacanth, microcrystaine2ncrease the viscosity of the e#terna e#terna phase Ipward creaming Ta&es pace in unstabe emusion in which the interna phase has a esser density tha

phase

ore destructive to an emusion than creaming4



ore destructive to an emusion than creaming4oaescence of the gobues of the interna phaseSeparation of that phase into a ayer <rea&ingseparation of the interna phase from the emusion2rreversibe because the protective sheath about the gobues of the interna phase

0ree%ing, thawing and e#cessive heat coarsen an emusion and sometimes brea& it The industry performs tests at , , and c to determine the productJs stabiiStabiity at both and for 7 months is considered minimaShorter e#posure periods at may be used as an aternative test Steps to minimi%e ha%ards to stabiity0or ight sensitive emusions, use ight resistant containers

0or emusions susceptibe to o#idative decomposition, anti o#idants may be incudeabe warning provided to ensure that the container is tighty cosed after use0ungi (mods and yeasts) are more i&ey to contaminate emusions than are bacterpreservatives are incuded in the a$ueous phase of an oFw emusionEx. ethyparaben, propyparaben5coho ('6E-'E) is added to oFw emusion for preservation



shoud not be used when nausea, vomiting, or abdomina pain is present because th



g p pindicate appendicitis, and use of a a#ative coud rupture the appendi#commercia castor oi emusions vary from 7E to WREadut dose4 mH chidren (6 -W yFo)4 ' m4 chidren ess than 6 yFo4 mbest ta&en on an empty stomach foowed by one fu gass of water Simethicone emusion

@ater-dispersibe form of simethiconeIses4Defoaming agent- reief of painfu symptoms of e#cessive gas in the .2T@or&s in the stomach and intestines by changing the surface tension of gas bubbescoaesce, freeing the gas for easier eiminationmusion in drop form- reief of gas in infants due to coic, air swaowing, actose intEx. yicon drops mgF!Wm5ntacid formuations

Ex. yanta E&amples of topical emulsions9and and body otionIsed to treat dry s&inoFw emusionappied to the outer surface of the body

Ex. strasorb (estradio)- treatment of hot 1ashes and night sweats accompanying by repacing the hormones ost during menopause



by repacing the hormones ost during menopauseorticosteroid-containing emusionsEx. 8otrimin 50 (cotrima%oe), Diproene (augmented betamethasone dipropionate)ShampooIsed to cean the hair and scapay contain 5P2 Aels and #amas ade up of sma inorganic partices or arge organic moecues encosing and interpi$uidSemirigid system in which the movement of the dispersing medium is restricted by adimensiona networ& of partices or sovated macromoecues of the dispersed phaseincreased viscosity caused by the interacing and conse$uentia interna friction is resemisoid state

may consist of twisted matted strands often wound together by stronger types of vato form crystaine and amorphous regions throughout the system (tragacanth, )concentration of geing agents4 Y'E (!O-6!E range)cooida dispersion

Singe-phase gesges in which the macromoecues are distributed so that no apparent boundaries e#

a ma or i&



)olloidal dispersionssol- term to designate a dispersion of a soid substance in a i$uid, soid, or gasemediumH soid-i$uid dispersion systemhydro" hydrosoH wateralco- acosoH acoho

aerosol- a dispersion of a soid or i$uid in a gaseous phasea substance is said to be cooida when the partices fa between 'nm and !m

Di?erence between cooida dispersions and true soutions

)olloidal dispersions <rue solutions

9arer particle size smaer partice si%e

Opa8ue particlesB scatterlihtB tur(id

Do not scatter ightH cear

2mportant criterion for estabishing the cooida statepartice si%enature of the dispersing phase



8yophiicsovent ovingdisperse phase interacts appreciaby with the dispersion mediumeasier to preparegreater stabiity8yophobicsovent hatingdegree of attraction is smaEx. Starch is yophiic in water but yophobic in acoho 9ydrophiic-

9ydrophobic-5ssociation or amphiphiic cooidgrouping of moecues that e#hibit both yophiic and yophobic propertiesform dispersions on both a$ueous and non a$ueous media



8yophiic cooidsarge organic moecues capabe of being sovated with moecues of the dispersidisperse readiy upon addition to the dispersion medium to form cooida dispersmore moecues are added, viscosity increaseshigh concentration of moecues, i$uid soution may become semisoid or soid d

Ex. .echange in temperature causes ges to resume to i$uid statebecomes 1uid on agitationresume their soid state after remaining undisturbed over a period of time Thi#otropy

8yophobic cooidscomposed of inorganic particesthere is a itte interaction when these are added to the dispersing phasedo not spontaneousy disperseaddition to the dispersion medium does not greaty a?ect the viscositysovation depends on the character and nature of the dispersing mediumincrease viscosity of the dispersing medium, increase in concentration



atura cooidssef dispersing upon addition to the dispersing mediumEx. 5cacia 5rti+cia cooidsre$uire +ne puveri%ation of coarse partices to cooida si%e by a cooid mi or a

cooida si%e partices may be forms by chemica reaction under highy controed <erminoloy related to els2mbibition- ta&ing up of a certain amount of i$uid without measurabe increase inSweing- ta&ing up of a i$uid by a ge with an increase in voume

ony i$uids that sovate a ge can cause sweingsweing of protein ges is in1uenced by p9 and the prescenceof eectroytes

Syneresis- occurs when the interaction between partices of the dispersed phase that on standing, the dispersing medium is s$uee%ed out in dropets and ge shrin2nstabiity in a$ueous and non a$ueous

Thi#otropy- reversibe geH-so formation with no change in voume or temperature1owLeroge- formed when the i$uid is removed from a ge and ony the framewor& rEx. Tragacanth, geatin sheets, ribbons, acacia tears





E&amples of ellin aents




,linic acid

-obtained from seaweed

- tasteess and odoress

-white to yeowish white +brous powder

-used in concentration at about '-E

-swes in water to about 6-7 times its own weight without dissoving

- premi#ing with another powder aid or other water miscibe i$uids aids in dispers

)ar(omer /car(opol0

-Ise in variety of dosage forms, incuding controed =reease tabets, ora suspen

ges- 0u?y white dry powder with arge bu& densities

arbomer Z7 = highy e?ective in thic& formuation, such as viscous ges!

arbomer Z7b- same as carbomer Z7 but intended for ora and mucosa appicamost widey used in pharmaceutica industry!

arbomer Z- forms spar&ing cear water or hydroacohoic gesH the most e3cie

carbopo resins and has a very good nondrip properties




-ge viscosity aso depend on the presence of eectroyte and p9!

-arbomer preparation are primariy used in the a$ueous system

- tends to form cumps of partices when hapha%ardy dispersed in a poar sovent

-to achieve fast dispersion of i$uid, add sowy the +ney divided powder to the vorte# of the i$uid whi

ote4 The goa is to prevent cumping by sowy sprin&ing the powder over the rapid agitation of watereutrai%er- added to thic&en the ge! a/9 and G/9, used in carbomer dispersion containing Y6E ac

Triethanoamine, wi neutrai%e carbomer resins containing up to E ethano!

)#) Sodium

-soube in water at any temperature

-sat of can be dispersed with high shear in cod water before the partices can hydrate and swe taggomerating to umps!

-once the powder is dispersed the soution is heated at about W[c for faster dissoution! These dispersip9 changes due to carbo#yate groupF

)olloidal Silicon Dio&ide

"can be used with other ingredints with simiar refractive inde# to prepare transparent ges

-absorbs arge $uantity of water without i$uefying

-wi form ge when combined with '-dodecano, prepared by adding siica to the vehice and sonicating and seaing for about [c overnight!





Aelatin

-dispersed in hot water and cooed to form ge! 5s an aternative, moisten the geatan organic i$uid that wi not swe!

#4 thy acoho, propyene gyco

#anesium aluminum silicate or @eeum

-in conc! of about 'E forms a thi#otropic ge

-the materia is inert and with few incompatibiities, best use above p9 7!

-may bind to some drugs and imit their bioavaiabiity

#ethylcellulose

-ong-chain substituted ceuose can be used to form ge in conc! at about E

-hydrates sowy in hot water

-anhydrous acoho or propyene gyco may be used to to prewet powders

-a#imum carity and fuest hydration and highest viscosity wi be obtained when

Plasti(ase or elene

i#ture of E ow @ poyethyene and ZE minera oi





Polo&amer or Pluoric

.es are made from sected forms of poyo#yethyene-poyo#ypropyene copoymeranging 'E-E

@a#y white free 1owing graues

/doress and tastess

ommony used poo#amers incude the4 '6 (8-grade),'QQ(0-WQgrade),67R (0-QRgrade),77Q(0-'Qrade),R (0-'6R grade)! \0J-1a&e form, \8K =i$uid form! P@,

"Ised at conc! 5t about 6!E :eies in the preparation of various :eies that dry appied to s&in

-<ora#- good agent that wi ge PC5 soutions

Povidone

-can be used to prepare ges in concentrations of about 'E

-compatibe in soution with wide range of inorganic sats,natura and synthetic re

-use to increase soubiity of poory soube drugs






E&amples of #amas and Aels



'entonite #ama%NF

-preparation of E ben%onite, a native hydrated cooidahydrated auminum siicate, in puri+ed water

- may be prepared mechanicay in a bender, or bysprin&ing the bentonite!

-insoube in water-swes appro#! '6 times its voume

-thi#otropic ge!

-Suspending agent

,luminum hydro&ide el

-a$ueous suspension of geatinous precipitate

-prepared by chemica reaction

-5uminum source of reaction is auminum choride, whichyieds the insoube 5/7 and auminum hydro#ide ppt!

-ISP permits the addition of sweeteners, 1avorants, andantimicrobia agents!

- antacid preparation is white viscous suspension, usefu intreatment of hyperacidity and peptic ucer!

Disadvantage4 constipating e?ects!

-5(/9)7 interferes with bioavaiabiity of tetracycine

#il$ of #anesia

-Preparation containing R-Q!E

-may be prepared by reaction bagnesium sufate

-product is produce by hyrdratio-opa$ue white viscous preparatproportions of water separate o

-shoud be sha&en before use!

-1avoring ois may be added

-possess reasonabe acid-neutr

-Side e?ect4 DiarrheaStarch lycerite

"used as topica vehice and pro

9u(ricatin Celly Formula

-use to assist in medica proced

-aid in insertion of various devic

-vehice for some product






)lear ,8ueous Ael :ith Dimethicone

-commony used as vehice fore#temporaneousy compounded products

Polo&amer Ael 'aseCehice for e#temporaneous products!

2n a combination with isopropy pamitate andecithin!

5bsorption enhancing topica vehice!

,EROSO9S-pressuri%ed dosage forms that, upon aa +ne dispersion i$uid or soid materiPressuri%ed pac&age4 commony used to an aeroso containerSpace sprays]aeroso use to provide Surface spaysFsurface coating- aeroso

carry active ingredient to surface TMPS /0 5;/S/82nhaation aerosos- commony &nowndose inhaer4intended to produce dropinhaation through the mouth and deppumonary treeasa aerosos-intended to produce +ndeivered through the nasa vestibue on nasa cavity8ingua aerosos-intended to produce dposition on the surface of the tongue Topica aerosos- produce +ne particeintended for appication to the s&in

<he aerosol principle*an aeroso formuation consists of 6 components!Product concentrate is the acti e ingredient of the aeroso combined ith the re$ui



Product concentrate- is the active ingredient of the aeroso combined with the re$uias antio#idants, surface-active agents, and sovents, to prepare a stabe and e3caciPropeant- when the propeant is a i$ui+ed gas or a mi#ture of i$ui+ed gases, it fredua roe of propeant and sovent or vehice for the product concentrate!

E&amples of propellants*arbon dio#ide

itrogenitrous o#ide0uorinated hydrocarbons4 trichoromono1uoromethane, dichorodi1uoromethane,dichorotetra1uoroethane, monochorodi1uoroethane, , octa1uorocycobutane*0 (choro1uorocarbon)4 phased out as a propeant,erosol systems* The pressure of aeroso is critica to its performance! 2t can be controed by The type and amount of propeant The nature and amount of materia compromising the product concentrate Space aerosols- usuay operate at pressures between 7 to psig (pound per s$6' degrees and may contain as much as QE propeant! Surface aerosols- commony contain 7 to RE propeant with pressures betwat 6' degrees Foam aerosols- usuay operate between 7W and psig at 6' degrees and mW to 'E propeant!

<:o"phase systemsonsists of the li8uid phase containing the i$ue+ed propeant and product concenphase



phase! <hree"phase systemsonsists of a layer of :ater immisci(le li8uid propellant, a layer of hihly a8uconcentrate, and the vapor phase!

)ompressed Aas Systemsompressed rather than i$ui+ed gases may be used to prepare aerosos! The pressure of the compressed gas in the head space of the aeroso container forceconcentrate up the dip tube and out of the vave! The use of gases that are insoube in the product concentrate wi resut in emissionessentiay the same form as it was paced in the container!E&amples of ases* itrogen, arbon dio#ide and nitrous o#ide ,erosol container and valve assem(ly?ectiveness of a pharmaceutica aeroso depends on achieving the proper combinacontainer% and valve assem(ly! The formuation must not chemically interact with the container or vave componinstabiity! 2t must be corrosive resistant!Cave must contribute to the form of the product to be emitted!

)ontainers*

<he selection of containers for an aerosol product is (ased on*2ts adaptabiity to production methodsompatibiity with formuation components



ompatibiity with formuation components5biity to sustain the pressure intended for the product The interest in design and aesthetic appea on the part of the manufacturerost @alve assem(ly

2t permits the e#pusion of the contents of the can in the desired form, at the desiredcase of metered vaves, in the proper amount or dose! The materias used in the manufacture of vaves must be inert to the formuations aapproved (y the FD,! The materias used in ma&ing vave parts are plastic% ru((er% aluminum% and sta <he usual valve assem(ly is composed of the follo:in parts*5ctuator

Stem.as&etSpringounting cup9ousingDip tube #etered"dose inhalers

m o ed when the formuation is a otent medication! e#am e is inhaation thera

The integrity of the chamber is controed by the dual valve mechanism!5 uni$ue transingua aeroso formuation permits the patient to spray dropets onto tongue The product is not inhaed



tongue! The product is not inhaed! Fillin operations The two features used in +ing the aerosos with propeant are4<y cooing beow their boiing point<y compressing the gas at room temperature

)old ;llin2n the cod method, both the product concentrate and the propeant must be cooedcesius to - degrees cesius! This temperature is necessary to i$uify the propean The cooing system may be a mi#ture of dry ice and acetone!

Pressure ;llin The concentrate is $uantitativey paced in the aeroso container, the vave assemb

crimped into pace, and the i$ui+ed gas, under pressure, is metered into the vave spressure burette! 5fter the container is +ed with su3cient propeant, the vave actproper function! The most used for most pharmaceutica aerosos!5dvantage4 ess danger of moisture contamination and ess propeant is oss in the <estin the ;lled containers*5fter +ing by either method, the aeroso container is tested under various environmfor4

The valve dischare rate is determined by discharging a portion of the contents oweighed aeroso during a period and cacuating, by the di?erence in weight, the gradischarged per unit of time



discharged per unit of time!Proper functions of the vavePartice si%e distribution of the spray0or accuracy and reproducibiity of usage when using metered vaves Pac$ain% la(elin and storae

9ave a protective cap that protects the vave against contamination with dust and#edicinal aerosols abeed with pastic pee-away abes or easiy removed paper For safety% abes must be warm users not to puncture pressuri%ed containers, not them near heat or an open 1ame and not to incinerate them!<emperatures a(ove 16 derees celsius% may be burst an aeroso containers!Recommended for storae (et:een +2 derees celsius and .7 derees celsSha&ing before use, hoding at the proper angeShoud maintain protective caps aways to prevent accidenta activation of vave ass <opical aerosols5erosos pac&ages for topica use on the s&in incude45nti-infective agents- povidone iodine, tonaftate, and thimerosa!5drenocortica steroids- betamethasone dipropopionate and vaerate, de#amethasontriamcinoone acetonide8oca anesthetic- dibucaine hydrochorideProvides patient a conevenient manner of appying the drug!

@ainal and rectal aerosols5eroso foams- commerciay avaiabe containing estrogenic substances and contra#ampe4 Proctofoam- contains proma#ine hydrochoride- use to reieve in1ammator



#ampe4 Proctofoam contains proma#ine hydrochoride use to reieve in1ammator

Foams2s an emusion dosage form containing dispersed gas bubbes!Pac&aged in pressuri%ed containers2ntended for appication to the s&in or mucous membranes!

Surfactants are used to ensure the dispersion of the gas and the two phases!2ntended to treat severey in:ured s&in or open wounds must be sterie! Preparation of foams0oams may contain one or more 5P2, surfactants, a$ueous or non-a$ueous i$uids an2f the propeant is in the internal% or discontinous phase a stabe foam is discha2f the propeant is in the e&ternal% or continous phase a $uic& brea&ing foam is Shoud be propery abeed especiay the 1ammabe foams!

Documents

Phardose Report Final