PHRM 309 PresentationPHRM 309 PresentationTopic: Liquid-liquid extractionTopic: Liquid-liquid extraction

Group members:Group members:1.1. Shahriar Rahman (ID: 2006-1-70-008)Shahriar Rahman (ID: 2006-1-70-008)

2.2. Thamina Hossain Pinky (ID: 2006-1-70-007)Thamina Hossain Pinky (ID: 2006-1-70-007)

3.3. Farzana Khan (ID: 2005-3-70-030)Farzana Khan (ID: 2005-3-70-030)

4.4. Nazrana Parvin (ID: 2005-2-70-096)Nazrana Parvin (ID: 2005-2-70-096)

5.5. Samiha Raisa Karim (ID:)Samiha Raisa Karim (ID:)

What is liquid-liquid extraction?What is liquid-liquid extraction?

Liquid-liquid extraction is a versatile and Liquid-liquid extraction is a versatile and dependable separation technique wherein dependable separation technique wherein an aqueous solution is usually brought into an aqueous solution is usually brought into contact with another organic solvent contact with another organic solvent exclusively immiscible with the former so exclusively immiscible with the former so as to affect legitimate and actual transfer as to affect legitimate and actual transfer of either one or more solutes into the of either one or more solutes into the latter. latter.

The Nernst Distribution LawThe Nernst Distribution Law

The Nernst Distribution Law or the Partition Law The Nernst Distribution Law or the Partition Law states that a neutral species will distribute states that a neutral species will distribute between two immiscible solvent with a constant between two immiscible solvent with a constant ratio of concentration. ratio of concentration.

KKpp=C=Coo/C/Caqaq

KKpp is the distribution constant or the partition is the distribution constant or the partition coefficient or partition ratio (solvent-to-feed ratio) coefficient or partition ratio (solvent-to-feed ratio)

CCoo is the concentration of the analyte in the is the concentration of the analyte in the organic phase (Solvent)organic phase (Solvent)

CCaqaq is the concentration of the analyte in the is the concentration of the analyte in the aqueous phase (Feed)aqueous phase (Feed)

Limitations of Partition LawLimitations of Partition Law

It is solely applicable to very dilute It is solely applicable to very dilute solutions.solutions.

It does not hold good when the distributing It does not hold good when the distributing substances encounter association or substances encounter association or distribution in either phases.distribution in either phases.

In liquid-liquid extractions the following In liquid-liquid extractions the following two two aspects are very crucial and important:aspects are very crucial and important:

1.1. Error due to the volume change: There are a Error due to the volume change: There are a number of number of procedure have been adopted to avoid ‘error due to the procedure have been adopted to avoid ‘error due to the volume change’ incurred thereby:volume change’ incurred thereby:

Measure the volume of the phase employed for the analysis Measure the volume of the phase employed for the analysis and incorporate this volume in the calculations.and incorporate this volume in the calculations.

Separate the phase quantitatively and subsequently dilute Separate the phase quantitatively and subsequently dilute to a known volume,to a known volume,

Separate the phase quantitatively and make use of the Separate the phase quantitatively and make use of the entire volume in the remaining steps of the ongoing entire volume in the remaining steps of the ongoing analysis, andanalysis, and

Carry a marker substance through the extraction to Carry a marker substance through the extraction to automatically compensate for volume changes. automatically compensate for volume changes.

In liquid-liquid extractions the following In liquid-liquid extractions the following two two aspects are very crucial and important:aspects are very crucial and important:

2.2. Effectiveness of an extraction: Based on the Effectiveness of an extraction: Based on the appropriate partition coefficient of an appropriate partition coefficient of an immiscible solvent pair it is possible to immiscible solvent pair it is possible to calculate the ‘effectiveness of an extraction’.calculate the ‘effectiveness of an extraction’.

Let us assume that ‘Let us assume that ‘xx’ moles of solute present ’ moles of solute present initially in a volume Vinitially in a volume V22 of Solvent ‘ of Solvent ‘bb’. Now, this ’. Now, this particular sample undergoes extraction with a particular sample undergoes extraction with a volume Vvolume V11 of Solvent ‘a’ and subsequently ‘ of Solvent ‘a’ and subsequently ‘yy’ ’ moles of compound are left in Vmoles of compound are left in V22 at at equilibrium.equilibrium.

Substituting these values in partition coefficient Substituting these values in partition coefficient equation :equation :

Continuation…Continuation…

The fraction extracted is absolutely The fraction extracted is absolutely independent of the initial solute concentration. independent of the initial solute concentration. So, the fraction left unextracted after ‘n’ So, the fraction left unextracted after ‘n’ extraction may be given by the following extraction may be given by the following expression,expression,

Solvent selection criteriaSolvent selection criteria

1.1. Miscibility: The two solvents should be immiscible with each Miscibility: The two solvents should be immiscible with each other. We cannot use solvents that are miscible with water e.g. other. We cannot use solvents that are miscible with water e.g. acetone, acetonitrile, pyridine etc.acetone, acetonitrile, pyridine etc.

2.2. Density: Large density differences between two solvents is Density: Large density differences between two solvents is favoured for good extraction process. More dense solvent will favoured for good extraction process. More dense solvent will form the lower layer and less dense solvents will form the upper form the lower layer and less dense solvents will form the upper layer with water when mixed with water e.g. ethyl ether has a layer with water when mixed with water e.g. ethyl ether has a density of 0.7133 g/mL at 20density of 0.7133 g/mL at 20°° and would constitute the upper and would constitute the upper phase when combined with water which has a density of 0.9982 phase when combined with water which has a density of 0.9982 g/mL. g/mL.

3.3. Solubility: Although immiscible solvents may form two visibly Solubility: Although immiscible solvents may form two visibly distinct phases when mixed together, they are often somewhat distinct phases when mixed together, they are often somewhat soluble in each other and become mutually saturated when mixed soluble in each other and become mutually saturated when mixed together e.g. 1.6% of the dichloromethane is soluble in water . together e.g. 1.6% of the dichloromethane is soluble in water . Conversely , water is 0.24% soluble in dichloromethane .Conversely , water is 0.24% soluble in dichloromethane .

Factors influencing solvent extractionFactors influencing solvent extraction

A number of factors exert a positive A number of factors exert a positive influence on solvent extraction:influence on solvent extraction:

1.1. Effect of temperatureEffect of temperature

2.2. Effect of pH on extractionEffect of pH on extraction

3.3. Effect of ion-pair formationEffect of ion-pair formation

4.4. Effect of synergistic extractionEffect of synergistic extraction

Emulsion problemEmulsion problem

Emulsion may be defined as a dispersed Emulsion may be defined as a dispersed system containing at least two immiscible system containing at least two immiscible liquid phases. liquid phases.

Emulsion formation is a serious problem Emulsion formation is a serious problem encountered during the extraction of drugs encountered during the extraction of drugs from biological as well as pharmaceutical from biological as well as pharmaceutical formulations. Emulsion formation makes formulations. Emulsion formation makes the separation of the two phases difficult. the separation of the two phases difficult.

Factors responsible for slow-Factors responsible for slow-coalescence of an emulsion coalescence of an emulsion

1.1. Finely divided powders, albumin, gelatin and natural Finely divided powders, albumin, gelatin and natural gums have a tendency to coat the droplets formed in gums have a tendency to coat the droplets formed in an emulsion which ultimately prevent them from an emulsion which ultimately prevent them from coalescing.coalescing.

2.2. Surfactants decrease the interfacial tension between Surfactants decrease the interfacial tension between the two immiscible liquids which help in stabilizing an the two immiscible liquids which help in stabilizing an emulsion.emulsion.

3.3. Ionic species may get absorbed at the interface of two Ionic species may get absorbed at the interface of two immiscible layers resulting in the formation of a net immiscible layers resulting in the formation of a net charge on the droplets. As the droplets attain a similar charge on the droplets. As the droplets attain a similar charge they repel each other preventing coalescence. charge they repel each other preventing coalescence.

Substances which stabilize emulsionsSubstances which stabilize emulsions

Some natural and synthetic substances Some natural and synthetic substances are used in the formulation of drugs are used in the formulation of drugs which are found to stabilize emulsions which are found to stabilize emulsions by:by:

1.1. Coating the tablets e.g. starch, acacia. Coating the tablets e.g. starch, acacia. silica, gelatin, finely divided talc.silica, gelatin, finely divided talc.

2.2. Minimizing the interfacial tension e.g. Minimizing the interfacial tension e.g. mono- & di-glycerides, stearates, mono- & di-glycerides, stearates, sorbitan monoleate.sorbitan monoleate.

Ways to prevent emulsion formationWays to prevent emulsion formation

1.1. Cautious & gentle agitation besides employing a sufficiently Cautious & gentle agitation besides employing a sufficiently large liquid-liquid interface to obtain a good extraction.large liquid-liquid interface to obtain a good extraction.

2.2. Removal of any finely divided insoluble material in a liquid Removal of any finely divided insoluble material in a liquid phase must be done by filtration before performing phase must be done by filtration before performing extraction.extraction.

3.3. Using solvent pairs having a large density difference & a Using solvent pairs having a large density difference & a high interfacial tension.high interfacial tension.

4.4. When performing extraction from water always ensure not When performing extraction from water always ensure not to work at pH extremes particularly at high/basic pH to to work at pH extremes particularly at high/basic pH to avoid emulsification.avoid emulsification.

5.5. Anion exchangers, alumina or silica gel are used in case of Anion exchangers, alumina or silica gel are used in case of acute emulsion problems. acute emulsion problems.

Breaking of an emulsion (coalescence)Breaking of an emulsion (coalescence)

1.1. Mechanical meansMechanical means

2.2. CentrifugationCentrifugation

3.3. Addition of monovalent & divalent ionsAddition of monovalent & divalent ions

4.4. Ethanol or higher alcoholEthanol or higher alcohol

5.5. Sudden cooling of emulsion (thermal shock)Sudden cooling of emulsion (thermal shock)

6.6. Altering the ratio of solventsAltering the ratio of solvents

7.7. Silicone defoaming agentSilicone defoaming agent

8.8. Thin-bed of an adsorbentThin-bed of an adsorbent