Quality control tests for Quality control tests for EmulsionsEmulsions

EmulsionEmulsion

An emulsion is a biphasic liquid penetration containing An emulsion is a biphasic liquid penetration containing two immiscible liquids, one of which is dispersed as two immiscible liquids, one of which is dispersed as minute globules into the otherminute globules into the other..

Evaluation tests for emulsionEvaluation tests for emulsion

● ●Average globular size and size distributionAverage globular size and size distribution

● ●Number of globulesNumber of globules

● ●Rheological evaluationRheological evaluation

● ●Zeta potentialZeta potential

● ●In vitroIn vitro drug release drug release

● ●In vitroIn vitro stability study stability study

1 .Determination of particle size and particle count:

-It is performed by optical microscopy and Coulter counter apparatus.

2 .Determination of viscosity:

- -Determination of viscosity is done to assess the Determination of viscosity is done to assess the changes that might take place during agingchanges that might take place during aging..

- -The viscometers used: cone and plate The viscometers used: cone and plate viscometersviscometers..

Quality control tests for EmulsionsQuality control tests for Emulsions

- In case of o/w emulsions, flocculation of globules causes an - In case of o/w emulsions, flocculation of globules causes an immediate increase in viscosity. After this change, the consistency ofimmediate increase in viscosity. After this change, the consistency ofthe emulsion changes with time.the emulsion changes with time.

- In case of w/o emulsions, the dispersed phase particles flocculate - In case of w/o emulsions, the dispersed phase particles flocculate quite rapidly resulting in a decrease in viscosity, which stabilizesquite rapidly resulting in a decrease in viscosity, which stabilizesafter 5 to 15 days.after 5 to 15 days.

- As a rule, a decrease in viscosity with age reflects an increase of - As a rule, a decrease in viscosity with age reflects an increase of particle size due to coalescenceparticle size due to coalescence..

33 . .Determination of phase separation:Determination of phase separation:

- Phase separation may be observed visually or by measuring the - Phase separation may be observed visually or by measuring the volume of the separated phases.volume of the separated phases.

4. Determination of electrophoretic properties:4. Determination of electrophoretic properties:

- Determination of electrophoretic properties like zeta potential is- Determination of electrophoretic properties like zeta potential isuseful for assessing flocculation since electrical charges on particles useful for assessing flocculation since electrical charges on particles influence the rate of flocculation.influence the rate of flocculation.

- O/W emulsion having a fine particle size will exhibit low - O/W emulsion having a fine particle size will exhibit low resistance but if the particle size increase, then it indicates a sign of resistance but if the particle size increase, then it indicates a sign of

oil droplet aggregation and instabilityoil droplet aggregation and instability..

Assessment of emulsion shelf life:Assessment of emulsion shelf life:The final acceptance of an emulsion depends on stability, appearance, The final acceptance of an emulsion depends on stability, appearance, and functionality of the packaged product. Stress conditions employed and functionality of the packaged product. Stress conditions employed for evaluating the stability of emulsions:for evaluating the stability of emulsions:

1- Aging and temperature1- Aging and temperature-It is routine to determine the shelf life of all types of preparations by -It is routine to determine the shelf life of all types of preparations by storing them for varying periods of time at temperatures that are higher storing them for varying periods of time at temperatures that are higher than those normally encountered.than those normally encountered.- Cycling between two temperatures (4 and 45°C)- Cycling between two temperatures (4 and 45°C)- At elevated temperature: accelerates the rate of coalescence and - At elevated temperature: accelerates the rate of coalescence and creaming and this is coupled with change in viscosity. Most emulsions creaming and this is coupled with change in viscosity. Most emulsions become thinner at elevated temperature and thicken when allowed to become thinner at elevated temperature and thicken when allowed to come to room temperature.come to room temperature.- Freezing damage emulsion more than heating ?- Freezing damage emulsion more than heating ?Since, the solubility of emulsifiers is more sensitive to freezing than Since, the solubility of emulsifiers is more sensitive to freezing than heating. In addition, the formulation of ice crystals develops pressure heating. In addition, the formulation of ice crystals develops pressure that can deform the spherical shape of emulsion dropletsthat can deform the spherical shape of emulsion droplets..

22 - -Centrifugation:Centrifugation:

● It is accepted that shelf life under normal storage conditions can be ● It is accepted that shelf life under normal storage conditions can be predicted rapidly by observing the separation of the dispersed phase due predicted rapidly by observing the separation of the dispersed phase due to either creaming or coalescence when emulsion is exposed to to either creaming or coalescence when emulsion is exposed to centrifugation. centrifugation.

● Centrifugation at 3750 rpm for 5 hours = effect of gravity for one year.● Centrifugation at 3750 rpm for 5 hours = effect of gravity for one year.

● No serious deterioration at 2000-3000 rpm at room temperature.● No serious deterioration at 2000-3000 rpm at room temperature.

● Ultracentrifugation of emulsions creates three layers● Ultracentrifugation of emulsions creates three layers: : a top layer of a top layer of coagulated oil, an intermediate layer of un-coagulated emulsion, and an coagulated oil, an intermediate layer of un-coagulated emulsion, and an essentially pure aqueous layer. The force of ultracentrifugation does not essentially pure aqueous layer. The force of ultracentrifugation does not cause oil separation until it is high enough to break or rupture the cause oil separation until it is high enough to break or rupture the absorbed layer of emulsifier that surrounds each dropletabsorbed layer of emulsifier that surrounds each droplet..

a centrifuged emulsion with: surfactant sediment (a),a centrifuged emulsion with: surfactant sediment (a),aqueous layer (b),aqueous layer (b),emulsion layer (c),emulsion layer (c),close-packed oil droplets (d)close-packed oil droplets (d)..

Overview of the possible effects Overview of the possible effects during emulsion centrifugation for during emulsion centrifugation for O/W and W/O emulsionsO/W and W/O emulsions(a); flocculation (b), coalescence(a); flocculation (b), coalescence(c), fractionation according to (c), fractionation according to particle size distributionparticle size distribution(d), detection of the presence of a (d), detection of the presence of a surfactant aggregatesurfactant aggregate(e) (promoting emulsion creaming (e) (promoting emulsion creaming by the depletion effect)by the depletion effect)

33 - -Agitation:Agitation:● ● Simple mechanical agitation can contribute to the energy with which Simple mechanical agitation can contribute to the energy with which two droplets impinge upon each other. It is rarely appreciated how two droplets impinge upon each other. It is rarely appreciated how useful the evaluation of an emulsion by agitation at or near room useful the evaluation of an emulsion by agitation at or near room temperature can be.temperature can be.● It was already noted that excessive shaking of an emulsion or ● It was already noted that excessive shaking of an emulsion or excessive homogenization may interfere with the formation of an excessive homogenization may interfere with the formation of an emulsions. Agitation can also break emulsions. A typical case, is the emulsions. Agitation can also break emulsions. A typical case, is the manufacture of butter from milkmanufacture of butter from milk..

Quality control of suspensionQuality control of suspension

● ●A pharmaceutical suspension is a coarse dispersion in which A pharmaceutical suspension is a coarse dispersion in which internal phase is dispersed uniformly throughout the external internal phase is dispersed uniformly throughout the external phasephase..

● ●The internal phase consisting of insoluble solid particles which The internal phase consisting of insoluble solid particles which is maintained uniformly throughout the suspending vehicle is maintained uniformly throughout the suspending vehicle with aid of single or combination of suspending agentswith aid of single or combination of suspending agents..

● ●The external phase (suspending medium) is generally aqueous The external phase (suspending medium) is generally aqueous in some instance, may be an organic or oily liquid for non oral in some instance, may be an organic or oily liquid for non oral useuse....

Features Desired In PharmaceuticalSuspensions

1 .The suspended particles should not settle rapidly and sediment produced, must be easily re-suspended by the use of moderate amount of shaking.

2 .It should be easy to pour yet not watery and no grittiness.

3 .It should have pleasing odour, colour and palatability.

4 .It should be physically, chemically and microbiologically stable.

5 .Parenteral/Ophthalmic suspension should be sterilizable.

The following tests are carried out in the final quality The following tests are carried out in the final quality control of suspensioncontrol of suspension::

●Appearance Color, odor and taste

●Sedimentation volume

● Rheological measurement

● Zeta Potential measurement

● Physical characteristics such as particle size determination

●pH

Evaluation of suspensions

Suspensions are evaluated by determining their physical stability.Two useful parameters for the evaluation of suspensions are;

A- sedimentation volumeB- degree of flocculation

-The determination of sedimentation volume provides a qualitative means of evaluation.- A quantitative knowledge is obtained by determining the degree of flocculation.

Sedimentation volume volume

Since redispersibility is one of the major considerations in assessing the Since redispersibility is one of the major considerations in assessing the acceptability of a suspension, and since the sediment formed should be acceptability of a suspension, and since the sediment formed should be easily dispersed by moderate shaking to yield a homogenous system, easily dispersed by moderate shaking to yield a homogenous system, measurement of the sedimentation volume and its ease of redispersion measurement of the sedimentation volume and its ease of redispersion from two of the most common basic evaluative proceduresfrom two of the most common basic evaluative procedures..

The concept of sedimentation volume is simple. It considers the ratio of the The concept of sedimentation volume is simple. It considers the ratio of the ultimate or final height of sediment (Hultimate or final height of sediment (Huu) to the initial or original height ) to the initial or original height

(H(Hoo) of the total suspension before settling as the suspension settles in a ) of the total suspension before settling as the suspension settles in a

cylinder under standard conditions. The larger this fraction, the better is the cylinder under standard conditions. The larger this fraction, the better is the suspendabilitysuspendability..

F = HF = Huu/H/Ho o or Vor Vuu/V/Voo

F has values ranging from less than one to greater than one.

normally F < 1When F < 1 Vu < VoWhen F =1 Vu = Vo

The system is in flocculated equilibrium and show no clear supernatant on standing.

When F > 1 Vu > Vo

Sediment volume is greater than the original volume dueto the network of flocs formed in the suspension and soloose and fluffy sediment

Sedimentation volumeSedimentation volume

Degree of flocculation (Degree of flocculation (ββ))It is a very useful parameter for flocculation

Sedimentation behaviour of flocculated and deflocculated suspensions

In flocculated suspension, formed flocks (loose aggregates). flocculated suspensions sediment more rapidly. The volume of final sediment is thus relatively large and is easily redispersed by agitation.

In deflocculated suspension, individual particles are settling, so rate of sedimentation is slow which prevents entrapping of liquid medium which makes it difficult to re-disperse by agitation. This

phenomenon also called ‘cracking’ or ‘claying .’

Rheologic methodsRheologic methods Viscosity of suspensions is of great importance for stability and pourability of suspensions. As we know suspensions have least physical stability amongst all dosage forms due to sedimentation and cake formation.

So as the viscosity of the dispersion medium increases, the terminal

settling velocity decreases thus the dispersed phase settle at a slower rate

and they remain dispersed for longer time yielding higher stability to the

suspension. On the other hand as the viscosity of the suspension increases, it’s pourability decreases and inconvenience to the patients for dosing increases .

Thus, the viscosity of suspension should be maintained within optimum range to yield stable and easily pourable suspensions .

● ●A practical rheologic method involves the use of A practical rheologic method involves the use of Brookfield Brookfield viscometerviscometer mounted on a helipath stand. The T-bar spindle is mounted on a helipath stand. The T-bar spindle is made to descend slowly into the suspension, and the dial made to descend slowly into the suspension, and the dial reading on the viscometer is then measure of the resistance the reading on the viscometer is then measure of the resistance the spindle meets at various levels in a sedimentspindle meets at various levels in a sediment..

● ●Data obtained on samples variously aged and stored indicate Data obtained on samples variously aged and stored indicate whether undesired changes are taking place. This whether undesired changes are taking place. This measurement is made on undisturbed samples of different measurement is made on undisturbed samples of different ages. The results indicate how the particles are settling with ages. The results indicate how the particles are settling with timetime..

● ●In screening study, the better suspensions show a lesser rate of In screening study, the better suspensions show a lesser rate of dial reading with spindle turns, i.e., the curve is horizontal for dial reading with spindle turns, i.e., the curve is horizontal for a longer perioda longer period..

Electrokinetic techniquesElectrokinetic techniques ● ●An electrophoretic method that employed a micro-electrophoresis An electrophoretic method that employed a micro-electrophoresis

apparatusapparatus..

● ●Such instrumentation permitted measurement of the migration velocity of Such instrumentation permitted measurement of the migration velocity of the particles with respect to the surface electric charge or the familiar zeta the particles with respect to the surface electric charge or the familiar zeta potentialpotential..

● ●The evaluation of suspensions by electrokinetic methods showed that the The evaluation of suspensions by electrokinetic methods showed that the zeta potential changes upon the addition of additives and is related to zeta potential changes upon the addition of additives and is related to stabilitystability..

● ●The zeta potential was correlated to visually observed caking , zeta The zeta potential was correlated to visually observed caking , zeta potential was again determined by microscope electrophoresis. It was potential was again determined by microscope electrophoresis. It was found that certain zeta potentials produced more stable suspensions found that certain zeta potentials produced more stable suspensions

because aggregation was controlled and optimizedbecause aggregation was controlled and optimized . .

Particle size changesParticle size changes

● ●It used for stability testing purposesIt used for stability testing purposes..

● ●Particle size distributions are sometimes determined by Particle size distributions are sometimes determined by microscopic means. This method of necessity requires dilute microscopic means. This method of necessity requires dilute suspensions that are counted with the aid of an ocular gridsuspensions that are counted with the aid of an ocular grid..

Packaging and Storage of SuspensionsPackaging and Storage of Suspensions::

1 (Should be packaged in wide mouth containers having adequate air space above the liquid.

2 (Should be stored in tight containers protected from : freezing.

excessive heat & light.

3 (Label: "Shake Before Use" to ensure uniform distribution of solid particles and thereby uniform and proper dosage.

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