I am really interested in double emulsification method in microparticles preparation which is suitable for hydrophilic drugs, but I am having difficulties in encapsulating my relatively hydrophilic drug. My only explanation is that during the preparation, the droplets coalescence with each other in the emulsion. How can I overcome this problem?
Dear Aida! Your problem is similar to a problem of stability of a multiple emulsions in processes of liquid membrane extraction. You have to take the good stabilizer of the reverse emulsions (the Span-80 type, or polymeric surfactant) and concentration of background electrolyte have to be equal in internal and external water phases (to avoid destruction of an emulsion as a result of osmotic shock).
Dear Aida,
1-You might need to decrease the amount of energy fed into your system because putting in too much energy ( by increasing the sonication time or the sonication amplitude % or increasing the homogenization cycles) can increase the particle energy thus increase its frequency and in return increase the chances of particle coalescence.
2- Another main factor is the % and type of surface active agent (SAA) used. since the SAA plays a main role in the stabilization of the formed particles. I mean if the SAA if abundant and efficient it can somehow overcome the coalescence because once the particle re-separate the SAA has the ability to quickly re stabilize the particle.
3- You can check also increasing the external viscosity as sometimes this help retard the coalescence between the two particles.
4-You might consider increasing the particles' surface charge ( Zeta--potential) as this would consequently increase the particles repulsion forces.
5- Also if your drug is not highly lipophilic then why use the double emulsion technique in the first place; you might want to consider using the O/W as it is easier and actually the W/O/W is especially recommended for the highly lipophilic drug.
6-I highly recommend you to read this paper as it details all the points explained above.
Re-coalescence of emulsion droplets during high-energy emulsification
SM Jafari, E Assadpoor, Y He, B Bhandari - Food hydrocolloids, 2008 - Elsevier
All the best with your research .
Dear Aida,
Are you using an emulsifier agent? Because it could be useful.
The other thing is try different ratios in the phases w/o/w.
Try another solvent to dissolve the polymer.
Best,
Cristian
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Dear Aida,
I partly agree with D H Mobarak, but other factors can influence the drug loss during w/o/w preparation. One is the drug concentration in the first aqueous phase, because the increase of drug concentration inside will increase the drug loss by the increasing probability of ingredient leaking in case of direct contacting the inner w droplets with the outer water phase. The latter can happen both in case of the coalescence of the w/o droplets in the outer w phase, and even more probably during the attrition of the w/o droplets, when inner w droplets can come into direct contact with the outer w phase.
On my opinion, high dispersion energy is advantageous in the first emulsification (during preparing the w1/o emulsion) and moderate dispersion energy in the second one, when we prepare the second i.e. double emulsion (w1/o)/w2.
The ratio of interfacial surface tensions of the w1-o phase border to that of the o-w2 (where w1 is the inner, w2 is the outer aqueous phase) . In this respect the applied surfactants play major rules. (if necessary I can send the title of a relevant publication)
The mode and rate of solidification of the polymer in the middle oil phase also plays role. If e.g. the solidification takes place by solvent evaporation, the too rapid evaporation can produce mini bubbles in the polimer matrix, i.e. the produced micro/nano spheres remain porous allowing the leakage of the hydrophilic drug into the outer w phase. The latter porosity also influences the drug release kinetics during use of the final drug formula.
Have a good success in your research,
regards, Janos Gyenis
Dear D. Karanam
I am using polycaprolacton PCL as a polymer 1.5g in 15ml of Dichloromethane DCM, then i drop wise the drug solution 50mg/2ml Hcl 0.1N (with or without PVA 0.1% with molecular weight 89000) and emulsify the mixture by ultraturax with 15000 rpm for 5 min, after that i add this w/o emulsion into 50 ml of distilled water with 5% of tween 20 (or PVA 1% MW 89000), and it is homogenized again with ultraturax 6000 rpm for 2 min so w/o/w should be formed...I let the organic phase to evaporate by mechanical stirring 1000 rpm for 1 hour (2 or 3 hours)... but unfortunately like i said before the results are not as expected.. although i changed a lot of parameters (speed,time,polymer conc.,surfactants)
The time of evaporation of DCM is not enough for those 15 mL.
1.5 grams is a lot, could you try a lower scale. Also the speed of the ultraturax is too low for that high volume.
Best,
Cristian
Dear D. Alexander
I've added Span 40 7% to the organic phase with Tween 40 5% to the aqueous phase. and its adding has resulted in minimize dimensional but decrease the entrapment to 5%!!!
I really doubt with osmotic problem...Is it possible sucrose or Nacl adding to the outer aqueous phase, solve the problem!!!
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