I am preparing microspheres of PVA and Sodium alginate. But those are not hard. Those are appearing gel like. How to get hardened microspheres?
It can be due to multi factors such as method of preparation and drying. What method your are using?
add the crosslinker after when the emulsion is formed. Increase the crosslinking time and stirring speed.Consider the change of ratio of the PVA to sodium alginate. Change of crosslinker can be considered.
Luckily, we have worked on this method and it appears that problem may be in the separation or drying step. When nanoparticles are formed by crosslinking (also known as hardening) of emulsion droplets with glutaraldehyde, the continuous phase is oil. Upon centrifugation and subsequent removal of supernatant, pellet of nanoparticles will still contain significant amount of oil. Oil is viscous as compared to water and difficult to remove. To solve this problem, nanoparticles are washed with a solvent that is miscible with oil but did not dissolve/degrade nanoparticle (and drug too, if possible). After, 5-10 washings e.g. with ethanol, and drying, you will get nanoparticles in desired powder form. Moreover, it may be possible that you nanoparticles, formed as crossliniking of polymer in internal aqueous droplet, may still retain water. Thus, you will need to ensure complete removal of internal (water) and external phase (oil) to get free flowing powder.
Good luck,
Mubashar
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