Characterization of Polymer Adsorption onto Drug Nanoparticles Using Depletion Measurements and Small-Angle Neutron Scattering

Daniel J. Goodwin, Shadi Sepassi, Stephen M. King, Simon J. Holland, Luigi G. Martini, M. Jayne Lawrence*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Production of polymer and/or surfactant-coated crystalline nanoparticles of water-insoluble drugs (nanosuspensions) using wet bead milling is an important formulation approach to improve the bioavailability of said compounds. Despite the fact that there are a number of nanosuspensions on the market, there is still a deficiency in the characterization of these nanoparticles where further understanding may lead to the rational selection of polymer/surfactant. To this end small-angle neutron scattering (SANS) measurements were performed on drug nanoparticles milled in the presence of a range of polymers of varying molecular weight. Isotopic substitution of the aqueous solvent to match the scattering length density of the drug nanoparticles (i.e., the technique of contrast matching) meant that neutron scattering resulted only from the adsorbed polymer layer. The layer thickness and amount of hydroxypropylcellulose adsorbed on nabumetone nanoparticles derived from fitting the SANS data to both model-independent and model dependent volume fraction profiles were insensitive to polymer molecular weight over the range M-v = 47-112 kg/mol, indicating that the adsorbed layer is relatively flat but with tails extending up to approximately 23 nm. The constancy of the absorbed amount is in agreement with the adsorption isotherm determined by measuring polymer depletion from solution in the presence of the nanoparticles. Insensitivity to polymer molecular weight was similarly determined using SANS measurements of nabumetone or halofantrine nanoparticles stabilized with hydroxypropylmethylcellulose or poly(vinylpyrrolidone). Additionally SANS studies revealed the amount adsorbed, and the thickness of the polymer layer was dependent on both the nature of the polymer and drug particle surface. The insensitivity of the adsorbed polymer layer to polymer molecular weight has important implications for the production of nanoparticles, suggesting that lower molecular weight polymers should be used when preparing nanoparticles by wet bead milling since nanoparticle formation is more rapid but with no likely consequence on the resultant physical stability of the nanoparticles.

Original languageEnglish
Article numberN/A
Pages (from-to)4146-4158
Number of pages13
JournalMolecular Pharmaceutics
Issue number11
Publication statusPublished - 4 Nov 2013


  • Nanoparticle
  • nanosuspension
  • wet bead milling
  • small-angle neutron scattering
  • adsorption isotherm


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