Preparation of Biodegradable Microspheres

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Preparation of Biodegradable Microspheres

In my previous blog I gave a detail description about Biodegradable polymers in general and for parenetral purposes, in this blog I want to explain about preparation of   Biodegradable Microspheres.


In general Microspheres are by one of three methods:


Ø  freeze-drying

Ø  evaporation

Ø  Solvent-extraction-precipitation.

Ø  Lyophilisation using cryoprotectants






  Solvent-extraction equipment


An extremely porous structure was obtained by the freeze-dry and solvent-extraction-precipitation procedures. But as compared to the freeze-dry technique Solvent-extraction-precipitation process is some what economical, so this process and Evaporation techniques are widely used now a days. The sphericity, size, and yields of the microspheres were influenced by the preparation procedure, surfactant type and concentration, temperature of the continuous phase, polymer concentration in the dispersed phase, and ratio of marker to polymer. The most suitable processing conditions were a polymer concentration of 5-10%, a marker loading of 10%, 0.1% surfactant (suggested), and temperature adjustment of the continuous phase from 15 to 50 oC followed by the addition of the dispersed phase.


Some examples of Microsphere preparations are given below:

1)Preparation of Methylene blue and Prednisolone acetate microspheres 

Microspheres containing methylene blue and prednisolone acetate were prepared by many methods like Freeze-drying, Solvent-extraction-precipitation, Evaporation etc. The microspheres remained relatively intact during the in vitro release of methylene blue, confirming that the incorporated agent was confined to the walls of the porous network. The release therefore was believed to be governed principally by the solubility of the drug and the porosity of the matrix.

2)Preparation of BSA loaded PLGA microspheres:

                        BSA (Bovine serum albumin) loaded PLGA microspheres were prepared by a “Double Emulsion Solvent Evaporation technique”. PLGA was dissolved in 10 ml dichloromethane and emulsified with BSA aqueous solution using a homogenizer to form a primary emulsion (w/o). The polymer concentration in organic phase was 60 mg/ml and the BSA to polymer weight ratio 1:15. This primary emulsion was rapidly transferred into 25 ml of aqueous solution containing 3% w/v of PVA as an emulsifier and homogenized to produce a double (w/o/w) emulsion. The resultant double emulsion was magnetically stirred for 6 h at ambient room temperature to evaporate dichloromethane. The hardened microspheres were isolated by centrifugation and washed thrice using distilled water. Mannitol (1% w/v) was added before lyophilization to prevent aggregation of microspheres. The microspheres were stored at 4º until the time of evaluation.


3)Preparation of Naltrexone loaded PLGA microspheres:       

Naltrexone microspheres were prepared using a solvent evaporation method. The effect of different formulation parameters on drug release from microspheres was studied. Naltrexone matrix devices were prepared by compression of naltrexone microspheres at temperatures above the glass rubber transition temperature (Tg) of the polymers. 

Emulsification/solvent-evaporation method was used for preparation of naltrexone microspheres. Appropriate amounts of PLA were added to 10 ml methylene chloride to provide concentrations of 2.5%, 3%, 3.5%, and 4% w/v; then different amounts of naltrexone were dissolved in the polymer solution to give 1% to 2.5% w/v drug solutions to yield theoretical drug loading of 20%, 30%, 40%, or 50% w/w, respectively. The solution was then added drop-wise to a 200-mL aqueous phase solution containing 0.5% w/v poly vinyl alcohol (PVA), while the mixture was stirred by an overhead stirrer to form a stable O/W emulsion system at room temperature (25 ± 2°C). Stirring was continued for up to 5 hours to allow the evaporation of methylene chloride and the formation of solid micro-spheres. Microspheres were filtered, washed with distilled water, and dried overnight until no weight loss was observed.


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Figure 1. SEM photograph of PLA microspheres containing 30% Naltrexone     Figure 2. SEM photograph of PLA microspheres containing 50% Naltrexone




4)Preparation of Insulin loaded Alginate microspheres: 

Sodium alginate solution (2%) was prepared with distilled water, sodium tripolyphosphate (Na TPP) and CaSo4 1.9g in glycerol/water mixture were taken .The emulsification process was initiated by slowly transferring the alginate mixture containing hydrated sodium alginate, sodium polyphosphate and calcium sulphate in to  300ml of double filtered groundnut oil . The rpm optimized as 2000rpm for 1hr .The microspheres obtained were filtered and acetone with dried.

Definite quantity of   microspheres were weighed and placed in 15ml insulin solution and kept for 45 minutes at low temperature .Excess insulin is filtered off and dried at low temperature.


5)Preparation of Alg-chitosan microspheres:

The alginate microspheres prepared by the above procedure and loaded with insulin were taken and coated with 0.3% chitosan solution .The coating time was 10 minutes.  



SEM of a) Plain alginate microspheres b) alginate microspheres coated with chitosan



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kranthi kumar's picture

Dear Naveen,
Good presentation, YOu have mentioned the use of surfactant in the preparation. Can you mention what kind of surfactant is used ? I mean is it more hydrophobic or lyophobic ?
You have mentioned percentages of different ingredients, is it same for any kind of polymers ?




Zarrin Faria's picture

Nice blog...
My question is the microspheres produced by all the methods mentioned by you are of the same quality ??
Faria Zarrin
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Ranga Raju's picture

Dear Naveen,
Nice presentation, the proceses are interesting. Can you give some formulations names where this microspheres are used ?
and which method is used mostly for the preparation.
Rajan raju
" "

Rajan raju

Upadhyayula Kumar's picture

"Insulin loaded Alginate Microspheres" how are they and why are they used ? In what way is it beneficial than the other formulations available? Your presentation of the original pics of the equipments used is really awesome.