Dear Milad,

I have a paper entitled "PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug " published by Govender et al. in Journal of Controlled Release and found it to be helpful for answering your question.

In the mentioned study they made nanoparticles of water soluble drug (procaine HCl), however, the first technique they used suffered from precipitation of the drug and incomplete incorporation into the nanoparticles. They have investigated different approaches to overcome this drawback:

Approaches investigated for drug incorporation efficiency enhancement included the influence of aqueous phase pH, replacement of procaine hydrochloride with procaine dihydrate and the inclusion of excipients: poly(DL-lactide) (PLA) oligomers, poly(methyl methacrylate-co-methacrylic acid) (PMMA–MA) or fatty acids into the formulation. 

I suggest you read this paper (attached) which may help you to solve the problem with your nanoparticles.

Hoping this will be helpful,

Rafik

Dear Milad,

Drug precipitation from nanoparticles could be  one of these possibilities: insufficient surfactant added to solubilize the drug, the medium pH needs to be adjusted for maximum solubility, insufficient polymers and saturation solubility of the drug in the solvent systems used.

it has to be treated case by case, so more information on the drug, polymer concentrations, more insights I can get to guide you through.

Best wishes

Hamdy

Hi Milad,

You need to provide more information. What is your method of preparation, how about drug solubility in organic or aqueous phases, did you use TEM to check whether the precipitate that you see is drug or it is coming from larger, micro-sized particles that were also formed? Also if you're relying only on dynamic light scattering (DLS) (e.g. malvern zetasizer, Brookhaven nanosizer, ..etc) to make sure that you actually have nanoparticles, this may not be enough. You need (have to) use TEM (or SEM) to confirm it. 

Dear Milad,

You´re not giving a lot of information but it could be related to the nature of nanoparticle-drug interactions. Assuming you have polymeric nanoparticles, structural stabilization can be achieved by incorporating the drug into an amorphous polymer. The interactions between the two types of molecules control the solubility of these materials in each other and are accomplished by van der Waals forces and hydrogen bonds...etc. When the drug-polymer molecular interactions are comparable to the drug-drug and the polymer-polymer interactions, the polymeric component is able to solubilize the drug material and large amounts of drug can be incorporated in the polymer matrix without drug crystallization. On the other hand, when the drug-polymer interactions are weaker, the drug and the polymer have a preference to interact with the molecules of their own kind, which favors drug crystallization. You can use Differential scanning calorimetry (DSC) to study the physicochemical state and possible interactions of the drug loaded in nanoparticles.

Carina

Carina, you are right in case of supersaturation, however, if drug is below solubility limit particles cannot reduce it unless there are other molecules in solution causing this. It would be also possible drug is dissolved in micelles or present not dissolved but finely dispersed, drug is stabilized in continuous phase. Then introducing nanoparticles stabilizer will partition between surface of nanoparticles and the drug leading to drug precipitation.