title: Interaction studies between indomethacin nanocrystals and PEO/PPO copolymer stabilizers.
abstract: OBJECTIVE
  The lack of effective screening methods and systemic understanding of interaction mechanisms complicates the stabilizer selection process for nanocrystallization. This study focuses on the efficiency of stabilizers with various molecular compositions and structures to stabilize drug nanocrystals.
  
  
  METHODS
  Five structurally different polymers were chosen as stabilizers for indomethacin nanocrystals. The affinity of polymers onto drug surfaces was measured using surface plasmon resonance (SPR) and contact angle techniques. Nanosuspensions were prepared using the wet-ball milling technique and their physico-chemical properties were thoroughly characterized.
  
  
  RESULTS
  SPR and contact angle measurements correlated very well with each other and showed that the binding efficiency decreased in the order L64 > 17R4 > F68 ≈ T908 ≈ T1107, which is attributed to the reduced PPO/PEO ratio and different polymer structures. The electrostatic interactions between the protonated amine of poloxamines and ionized indomethacin enhanced neither the affinity nor the properties of nanosuspensions, such as particle size and physical stability.
  
  
  CONCLUSIONS
  A good stabilizer should have high binding efficiency, full coverage, and optimal hydrophobic/hydrophilic balance. A high affinity combined with short PEO chains (L64, 17R4) caused poor physical stability of nanosuspensions, whereas moderate binding efficiencies (F68, T908, T1107) with longer PEO chains produced physically stable nanosuspensions.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.forename: Alma
authors.initials: A
authors.lastname: Kartal-Hodzic
authors.forename: Huamin
authors.initials: H
authors.lastname: Liang
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D004347:Drug Interactions; D005079:Excipients / Q000737:chemistry / Q000378:metabolism*; D007213:Indomethacin / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011409:Propylene Glycols / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D005079:Excipients; C116176:PEO-PPO-PEO; D011108:Polymers; D011409:Propylene Glycols; D011092:Polyethylene Glycols; D007213:Indomethacin