Preparation methods for liposomes.

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Methods of preparation of liposomes.

Hello dear bloggers here I present my first blog of the month it covers the different methods used for the preparation as well as production of liposomes.

With the introduction given by my team-mate nandini about liposome i.e. ( I go ahead in discussing the method of preparation of the liposomes.

Liposomes are vesicles consisting of a lipid bilayer enclosing an aqueous compartment at the center. (1)

Liposomes are classified based on their structure as

1. Multi-laminar vesicles(MLV): made up of series of concentric bi-layer of lipid enclosing a small internal volume.

2. Oligolamelar vesicles(OLV): constitutes 2 to 10 bi layer of lipids surrounding a large internal volume

3. Unilamellar vesicle(ULV): single layer of lipids

4. Based on the size of the single layer they are further divide into the following types with in ULV as

* Small unilaminar vesicle: size of 20 to 40 nm

* Medium unilaminar vesicle: size of 40 to 80 nm

* Large unilaminar vesicle: size of 100 to 1000 nm

* Gaint unilaminar vesicle: size of more than 1000 nm

Preparation methods. (2)

1) Multi-laminar vesicles(MLV):

(a) Liquid hydration method:

* In this method a solution of lipid is taken and it is evaporated which leaves a film in the vessel on complete evaporation of the solvent .

* The film is hydrated with the solvent

* The solution so resulted is subjected to centrifugal force which produce liposomes

This method is not so advantageous as it involves very low loading of dose. The drug content can be increased by the use of immiscible solvent (petroleum ether or diethyl ether) to it.

(b) Solvent spherule method:

This method produces liposomes of uniform size distribution. It is achieved by the use of lipid dissolved hydrophobic solvent dispersed in the aqueous solvent.

2) Small unilaminar vesicle:

(a) Sanitation method:

In this method the multi laminar liposomes are taken ad they are subjected to sonication by bath type sonicator or probe type sonicator.

But the major drawback is that as we have selected the MLV which posses very small internal volume with in SMV so formed will also be having a small internal diameter.

(b) French pressure cell method:

* In this method the MLV are allowed to pass through a small orifice at a pressure of 20000 psi and a temperature of 4Oc. there is a reduction I nthe outer layers during the passage and wold result in SULV.

* egg phosphatidylcholine

+ 1.5 %w/v of cetyl tetramethylammonium(detergent)

+silica gel powder, zeolite ZSMS and zellite X,

The organic phase is evaporated and the film is reconstituted with 5 mM of Nacl.. this

3) large unilaminar vesicles: it has a very high encapsulation efficiency thus most of the drugs used to get liposome.

(i) solvent injection method:

(a) Ether infusion method: a lipid solution is prepared by dissolving g it in diethyl ether or ethanol/ ether . this solution is injected into the aqueous solution of material to be incorporated under reduced pressure and at a temperature of 55 to 60o c.

(b) ethanol injection method: the ehanolic solution of lipid was injected rapidly into excess of buffer solution. But so formed liposomes will have a a wide range of heterogeneity of 30-110 nm.

(ii) Detergent removal method: detergents are prepared at their critical miceller concentration to solubilize the lipids. Once the lipids are solubilized the detergent is evaporated by dialysis or by gel chromatography or other methods.

(iii) Reverse phase evaporation method: a w/o emulsion is prepared by a brief sonication of the two medium. The organic phase is subjected to high pressure to remove it. It results in the formation of an viscous gel. The liposomes will be formed when the residual solvent is evaporated with a reduced pressure under continuous rotary evaporation. We can achieve appreciably high encapsulation efficiency of about 65%. And with modified reverse phase evaporation method the encapsulation efficience can be increased to 80%.

(iv) Calcium induced fusion method: calcium addition to SUV will cause fusion of layers and will result in multi laminar spiral configuration. When EDTA is added to it that will result in the formation of LUV

(v) Microfluidization method: MLV are allowed to pass through the microluidizer at an inlet pressure of 40 psi thy are allowed to repeat the cyclying for 25 times or more that will result in the formation of small lamellar vesicles

(vi) Freeze-Thaw Method: the SUV are subjected to rapid freezing and then allowed for slow thawing. This leads to formation of LUV due to fusion of the SUV.

Production of liposomes in industries. (2)

Most of the methods proposed for the preparations of liposomes are not suitable for the for scale up purpose as the the complications like the nature of solvent, reproducibity, sterility plays a major role in ruling out many of the above proposed methods

Most commonly used methods at industrial level are:

1. Detergent dialysis method:

2. Microlludisation method.

3. Preliposomes

4. Freeze drying method

This blog is free from plagiarized material.


1. Biopharmaceutics and pharmacokinetics a treatise by D.M.Bramhankar and sunil B. jaiswal (first edition reprint 2005) 360-361.

2. "Liposomes preparation methods" a review by Mohammad riaz in Pakistan journal of pharmaceutical sciences vol.19(1), January 1996, pp.65-77.


About the Author

Narmadha's picture
Author: Narmadha


Sravani kompella's picture

Hello narmada, Your blog has very good informtion. But i want to know whether usage of liposomes is started in drug delivery or is it still in work.?
Narmadha's picture

hello sravani, thank you for your comment. yes the liposomes are marketd. and many are still in the clinical trails. in future we can expect a number of such formulations. please visit the folowing sites for the marketd formulations

With regards, Narmadha  

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