title: Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine.
abstract: OBJECTIVE
  The objective of this study is to develop a new solubility enhancement strategy of antipsychotic drug - perphenazine (PPZ) - in the form of its amorphous nanoparticle complex (or nanoplex) with polyelectrolyte dextran sulfate (DXT).
  
  
  CONCLUSIONS
  Poor bioavailability of PPZ necessitated the development of fast-dissolving PPZ formulations regardless of delivery routes. Existing fast-dissolving formulations, however, exhibited low PPZ payload. The high-payload PPZ-DXT nanoplex represents an attractive fast-dissolving formulation, as dissolution rate is known to be proportional to payload.
  
  
  METHODS
  The nanoplex was prepared by electrostatically driven complexation between PPZ and DXT in a simple process that involved only ambient mixing of PPZ and DXT solutions. We investigated the effects of key variables in drug-polyelectrolyte complexation (i.e. pH and charge ratio RDXT/PPZ) on the physical characteristics and preparation efficiency of the nanoplex produced. Subsequently, we characterized the colloidal and amorphous state stabilities, dissolution enhancement, and supersaturation generation of the nanoplex prepared at the optimal condition.
  
  
  RESULTS
  The physical characteristics of nanoplex were governed by RDXT/PPZ, while the preparation efficiency was governed by the preparation pH. Nanoplex having size of ≈80 nm, zeta potential of ≈(-) 60 mV, and payload of ≈70% (w/w) were prepared at nearly 90% PPZ utilization rate and ≈60% yield. The nanoplex exhibited superior dissolution than native PPZ in simulated intestinal juice, resulting in high and prolonged apparent solubility with good storage stabilities.
  
  
  CONCLUSIONS
  The simple yet efficient preparation, excellent physical characteristics, fast dissolution, and high apparent solubility exhibited by the PPZ-DXT nanoplex established its potential as a new bioavailability enhancement strategy of PPZ.
authors.affiliation: a School of Chemical and Biomedical Engineering, Nanyang Technological University , Singapore.
authors.forename: Bingxue
authors.initials: B
authors.lastname: Dong
authors.affiliation: a School of Chemical and Biomedical Engineering, Nanyang Technological University , Singapore.
authors.forename: Kunn
authors.initials: K
authors.lastname: Hadinoto
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D001682:Biological Availability; D003102:Colloids / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D005750:Gastric Juice / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010546:Perphenazine / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility
chemical_list: D014150:Antipsychotic Agents; D003102:Colloids; D004337:Drug Carriers; D016264:Dextran Sulfate; D010546:Perphenazine
keywords: Amorphization; antipsychotic drugs; perphenazine nanoparticles; poorly soluble drugs; supersaturation