Every nanoparticles formulation has a hydrophilic polymer as a surfactant such as PVA. When nanoparticles are centrifuged for separation, does not it cause the release of drug which is entrapped in PVA? This will result in low entrapment. Need expert opinion.
Yes, we have seen there exists a certain limit of mechanical strength to hold up inner molecules in the core of nano-capsules. But, co-precipitation technique can be adopted, with a relative lesser RPM, to separate them out from the solution.
It is usually not a problem under practical conditions. You might get a problem when part of drug is dissolved or dispersed in surfactant or polymer phase lighter than water.
Thank you. Under what conditions drug can dissolve or disperse in surfactant?
Dear Giulia,
If the polymer is covalently linked to NPs, polymer may not be affected by centrifugation, but I am not sure about the drug entrapment in PVA. Importantly, the rpm value matters. I recommend you to follow lesser rpm. If NPs are not separated, increase the centrifugation time maintaining less temperature. Hirak Chatterjee is absolutely right.
All the best..
Drug may get dissolved in surfactant micelles or even in undissolved surfactant (e.g. when nonionic surfactant is above cloud point temperature). Drug maybe also dispersed in water and stabilized by surfactant.
Dear all, I agree with Giulia Fulias. Many nanoparticles are made of hydrophilic polymer and their vitro drug release studies show faster (burst) drug release in start. I have seen in many papers that nanoparticles can significantly release drug (up to 20%) in first 30 minutes. Therefore, nanoparticles must have been releasing drug during washing steps when they are washed with water for 3-5 times; each washing step may involve redispersing nanoparticles in water and centrifuged for 5-10 minutes. Is it not a remarkable time period of exposure to water?
This may not be a problem for hydrophobic polymer or drug, but can be significant for water soluble agents.
If drug entrapped in NP's, chances of leaking are less during centrifugation. The solution may contain free drug, which need to be separated from entrapped drug. As previously discussed, you can centrifuge it at low RPM for more cycles.
Suruchi, all drug cannot be entrapped within NPs as there must be some surface associated drug. If we centrifuge at low speed, we will not be able to collect small size NPs. What do you think?
Giulia, did you study its PSD and PI? If so you will come to know the particle size distribution and its percentage and based on that you can worried for surface associated drug. You can also crosschecked by DSC profile. (with and without washing). I would suggest to do morphological study of NP's.
You can do one more thing, dissolved NP in any suitable solvent and check it concentration. And compare it with your regular procedure. The difference would suggest you something.
If you have an idea about particle size and density you will be able to calculate how long you will have to centrifuge at a defined acceleration for full nanoparticle separation (Stokes law). This will help you to select time and acceleration for not stressing the particle-polymer-drug composite too much.
Dear Suruchi Kokil, if we centrifuge at low speed, it will require more time of centrifugation. Thus, the release (or dissolution) of drug in washing amount of water will be more as it is a function of time.
Size of particles may also not help because nanoparticles density, porosity and shape will be different due to different materials and methods of preparation used.
Rehman, During centrifuge washing would only accommodate free drug not the entrapped drug. PSD along with morphology would help. I am talking about drug molecule not for drug carrier.
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