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A seminar onMULTIPLE EMULSIONSM NALINI KRISHNA REDDY M Pharm I Semester Department of Pharmaceutics.
INTRODUCTION An emulsion is a thermodynamically unstable systemconsisting of at least two immiscible liquid phases one ofwhich is dispersed as globules in other liquid phase stabilized by presence of an emulsifying agent Leon et al .
Emulsifying agents are ampiphillic in nature Emulsifiers assist in formation of emulsions by threemechanisms Leon et al 1991 Reduction in interfacial tension Formation of rigid interfacial film .
Electric repulsion MULTIPLE EMULSIONS These are polydispersed system where the drops of thedispersed phase themselves contain even smallerdroplets in most cases identical with a continuous phase .
Based on dispersed media multiple emulsions are of twotypes James et al 2002 w o w multiple emulsion o w o multiple emulsion According to seifriz even more complex multiple emulsions.
may occur like o w o w o or w o w o w but the stability is Certain multiple emulsions have been termed as liquidmembrane systems Jim et al 2003 FORMULATION OF MULTIPLE EMULSIONS.
Shende et al 2006 Mainly multiple emulsion are composed of For pharmaceutical use oils like refined hydrocarbon oils areused Such as light liquid paraffin and esters of long chain fattyacids including vegetable oils and mineral oils Example ethyl.
oleate isopropyl meristate olive oil arachies oil seasem oil Mixtures of oils can be used To reduce specific gravity To alter the viscous nature of the oil FORMULATION OF MULTIPLE EMULSIONS.
Selection of oil phase can affect various emulsionparameters Like Release profile Particle size Emulsion stability.
A novel o w o emulsion containing castor oil as internal oilphase and a floro carbon as an external oil phase hasbeen described for pulmonary delivery of the drug FORMULATION OF MULTIPLE EMULSIONSAqueous phase Sinha et al 2002 .
The two aqueous phases of w o w emulsions can be Simple aqueous solution of drugs Buffer solutions Aqueous suspensions of drug Gelled aqueous phase and.
Aqueous phases containing viscosity enhancers Increase and release rate of drug can be modified by changingthe pH of two aqueous phases Increase in difference of pH between two aqueous phases leads to instability .
FORMULATION OF MULTIPLE EMULSIONSSurfactants Florence et al 1982 Reduce interfacial tension between two phases w o or o winterface At least two surfactants are used for the preparation of multiple.
emulsions For w o w lipophilic surfactant act as primary emulsifier andhydrophilic as secondary emulsifier in case of o w o it is vice The optimum concentration of the surfactant to emulsify givenoil can be determined by the use of hydrophilic lipophilic.
balance HLB FORMULATION OF MULTIPLE EMULSIONSSurfactants Florence et al 1982 For primary surfactant the HLB valued should be in the range of2 7 and for secondary surfactant it is between 6 16 for a w o w.
Non ionic emulsifiers are preferred due to their low toxicity andthey do not react with ionic compounds Non ionic surfactants like spans and tweens have high HLBrange are used PREPARATION OF MULTIPLE EMULSIONS.
Two step emulsification or double emulsification method James et al 2002 Multiple emulsions may be prepared in a two stageprocedures by the re emulsification of a primaryemulsions .
First step is preparation of primary emulsion The second emulsification step is critical and excessmixing can fracture the drops resulting in simple emulsion A low sheer mixer may be employed with 1000 rpm for 15minutes in first step not more than 600 rpm for 5 minutes.
for second step PREPARATION OF MULTIPLE EMULSIONSFig Preparation of w o w type of multiple emulsions by two step method PREPARATION OF MULTIPLE EMULSIONSPhase Inversion or one step method .
Fig Preparation of multiple emulsions using phaseinversion technique PREPARATION OF MULTIPLE EMULSIONSMembrane Emulsification Method Charcosset et al 2004 Fig Schematic diagram of apparatus.
used for the multiple emulsionpreparation usingmembrane emulsification techniqueY 5 03X 0 19Y mean globule size.
X membrane pore size CHARACTERIZATION OF MULTIPLE EMULSIONS Shende et al 2006 Average globule size and size distribution Optical microscopy .
Coulter counter method Electron microscopy Average globule size of multiple emulsion ranges from2 5 micrometers Size distribution studies are done to know the movement.
of particles i e size distribution behaviors with time coalescence and flocculation CHARACTERIZATION OF MULTIPLE EMULSIONS The critical size of droplets for setting is given fromstokes law .
Rate of setting or creaming D2 18 dp dm g D particle diameter viscosity of the medium dp dm densities of particles and medium g gravitational constant.
CHARACTERIZATION OF MULTIPLE EMULSIONSArea of interphases The average globule diameter determined can be used inthe calculation of total area of interphase S 6 D S total area of interphase in sq cm D .
diameter of globule in cm Number of globules Number of globules per cubic millimeter can be measuredusing haemocytometer cell Number of globules mm3 number of globules x dilution x.
4000 number of small square counted Average droplet size should be in the range of 2 5 m CHARACTERIZATION OF MULTIPLE EMULSIONSYield or Entrapment Efficiency Sinha et al 2002 Yield is expressed in two ways.
Percentage of multiple droplets relative to simple Fraction of internal aqueous phase entrapped asmultiple droplets Factors affecting the yield of multiple emulsions Primary phase volume ratio.
Secondary emulsification time Mixing speed Secondary phase volume ratio Additives CHARACTERIZATION OF MULTIPLE EMULSIONS.
Determination of entrapment efficiency Internal phase tracer technique Dialysis Centrifugation Conducirtivty measurements.
Per cent of drug entrapped amount of drugentrapped total amount ofdrug X 100 CHARACTERIZATION OF MULTIPLE EMULSIONSRheology .
Jim et al 2003 By increasing the shear rate and shear time the apparentviscosity increased Further shearing caused increase in shear stress ofemulsion and induced phase inversion.
Reasons of phase inversion Increase in volume fraction of oil droplets byentrapment of water molecules Coalescence of oil droplets upon shearing STABILITY OF MULTIPLE EMULSIONS.
Emulsion stability is a phenomenon which depends uponthe equilibrium between water oil and emulsifier Unfortunately Multiple Emulsions are thermodynamicallyunstable Jim et al 2003 Some of the breakdown pathways that may occur in.
multiple emulsions are Coalescence of internal droplets Coalescence of multiple droplets Expulsion of internal droplets Shrinkage of internal droplets.
The causes for the instability of multiple emulsions are Migration of emulsifier Osmotic instability Creaming METHODS TO STABILISE MULTIPLE EMULSIONS.
The following methods can be used for stabilization ofmultiple emulsions Sinha et al 2002 Use of high viscous oils Polymerization and complexation of interfaciallyadsorbed surfactant molecules.
Gelation of oil or aqueous phases of the emulsion Liquid crystal stabilized multiple emulsion Stabilization in the presence of electrolytes Fig Various approaches to stabilize w o w multiple emulsion A stabilizing through liquid crystal formation.
B stabilization by interfacial polymerizationC stabilization by adsorption of electrolyte or adsorption or covalent anchoring of polymerD gelation of either internal or external phase or oil core STABILITY ASSESSMENT STUDIES Stability of multiple emulsions can be assessed in various.
aspects like Determination of particle size Determination of phase separation Measurement entrapped percentage and viscosity In vitro release studies .
Dialyzing the multiple emulsion packed in a dialysis tubeagainst a suitable dissolution media Conductometric method Fig Assembly use for invitro drug release In vivo evaluation .
Blood concentration data in rats and rabbits Urinary excretion data in man DRUG RELEASE FROM MULTIPLE EMULSIONS Release of drug from multiple emulsions occurs fromvarious mechanisms Pandit et al 1987 .
Diffusion of unionized drugs through the oil layer Carrier mediated transport Micellar transport Rapture of oil membrane Thinning of oil membrane.
Swelling and breakdown behavior BIOAVAILABILITY OF MULTIPLE EMULSIONS The administration of emulsions intravenously presence ofinteresting relationship between physicochemical propertiesand physiological response Walster 1993 .
The clearance of an emulsion from the blood is determinedlargely by its interaction with the reteculo endothelialsystem It can be stated that Fine particle size emulsions are cleared more slowly thancoarse particle size emulsions .
Negatively charged and positively charged particles arecleared more quickly than natural particles Emulsions stabilized by low molecular weight emulsifiersare cleared more rapidly than those stabilized by highmolecular emulsifiers .
APPLICATIONS OF MULTIPLE EMULSIONS Multiple emulsions are formulated for intravenous topical and oral administration Controlled and sustained drug delivery Improve in the bioavailability.
Drug targeting Vaccine adjuvant Hemoglobin multiple emulsion Masking of taste Drug overdose treatment.
Immobilization of enzymes Tropical and cosmetic use CONCLUSION Multiple emulsions are complex polydispersed systemswhere both oil in water and water in oil emulsion exists.
simultaneously which are stabilized by lipophillic andhydrophilic surfactants respectively The ratio of these surfactants is important in achievingstable multiple emulsions Among water in oil in water w o w and oil in water in oil o w o type multiple.
emulsions the former has wider areas of applications Various factors affecting the stability of multiple emulsionsand the stabilization approaches of multiple emulsionswere discussed in detail CONCLUSION.
Favorable drug release mechanisms and rate along within vivo fate of multiple emulsions make them a versatilecarrier It finds wide range of applications in controlled orsustained drug delivery targeted delivery taste masking bioavailability enhancement enzyme immobilization etc .
Multiple emulsions have also been employed asintermediate step in the microencapsulation process andare the systems of increasing interest for the oral deliveryof hydrophilic drugs which are unstable in gastrointestinaltract like proteins and peptides .
With the advancement in techniques for preparation stabilization and rheological characterization of multipleemulsions it will be able to provide a novel carrier systemfor drugs cosmetics and pharmaceutical agents REFERENCES.
James Swarbrick James C Boylan Encyclopedia ofPharmaceutical Technology Marcel Dekker Inc Vol 5 2 117 168 2002 Herbert A Lieberman Gilberts Banker Pharmaceuticaldosage forms Disperse systems vol 2 11 19 1995 .
Nissim Garti Abraham Aserin pharmaceutical Emulsions Double Emulsions and Microemulsions The HebrewUniversity of Jerusalem Jerusalem Israel 494 2001 Leon Lachman Herbert A Libertman Joseph L Kanig The Theory and Practice of Industrial Pharmacy 3 501.
534 1991 Sanjay kumar Goswami Multiple Emulsions An autoprocessing system for enzymes Pharmatimes vol 30 17 REFERENCES Charcosset c Limayem I Fessi H The membrane.
emulsification process A Review J Chem TechnolBiotechnology 79 209 218 2004 Walster P Emulsion Stability Encyclopedia of EmulsionTechnology Marcel Dekker vol 4 1 62 1996 .
Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. ... Encyclopedia of Pharmaceutical Technology, Marcel Dekker, Inc. Vol.5 (2) : 117-168 (2002).

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