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Pharmaceutical Amorphous Nanoparticles
Authors:Rajan Jog  Diane J. Burgess
Affiliation:Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269
Abstract:
There has been a tremendous revolution in the field of nanotechnology, resulting in the advent of novel drug delivery systems known as nanomedicines for diagnosis and therapy. One of the applications is nanoparticulate drug delivery systems which are used to improve the solubility and oral bioavailability of poorly soluble compounds. This is particularly important because most of the molecules emerging from the drug discovery pipeline in recent years have problems associated with solubility and bioavailability. There has been considerable focus on nanocrystalline materials; however, amorphous nanoparticles have the advantage of synergistic mechanisms of enhancing dissolution rates (due to their nanosize range and amorphous nature) as well as increasing supersaturation levels (due to their amorphous nature). An example of this technology is NanomorphTM, developed by Soliqus/Abbott, wherein the nanosize drug particles are precipitated in an amorphous form in order to enhance the dissolution rate. This along with other simple and easily scalable manufacturing techniques for amorphous nanoparticles is described. In addition, the mechanisms of formation of amorphous nanoparticles and several physicochemical properties associated with amorphous nanoparticles are critically reviewed.
Keywords:amorphous  nanoparticles  nanocrystalline  solubility  stability  dissolution  solid state  calorimetry  X-ray diffraction  bioavailability  ACN  amorphous chitin nanoparticles  API  active pharmaceutical ingredient  APTES  3-aminopropyltriethoxysilane  BCS  Biopharmaceutics Classification System  CGN  K-carrageenan  CMC  carboxymethyl cellulose  cps  centipoise  CTAB  cetrimonium bromide  DLS  dynamic light scattering  DMC  dimethyl chitosan  DoE  design of experiment  DS  dextran sulfate  DSC  differential scanning calorimetry  DTAB  dodecyl trimethylammonium bromide  EPL  ε-polylysine  FDA  food and drug administration  FTIR  Fourier transform infrared spectroscopy  GAS  gas antisolvent  HMW  high molecular weight  HPC  hydroxypropyl cellulose  HPβCD  hydroxypropyl β-cyclodextrin  HPMC  hydroxylpropylmethylcellulose  LMW  low molecular weight  MβCD  methyl-β-cyclodextrin  MCC  microcrystalline cellulose  MCM-41  mobile composition of matter no. 41  MMA  methyl methacrylate  MPTMS  (3-mercaptopropyl)trimethoxysilane  NME  nanoporous membrane extrusion  NPs  nanoparticles  O/W  oil in water  PBS  phosphate-buffered saline  PCL  polyε-caprolactone  PEG  polyethylene glycol  PEI  poly(ethylene imine)  PLA  polylactic acid  PLGA  poly(lactic-co-glycolic acid)  PLM  polarized light microscopy  PM  physical mixture  PSu  propylene succinate  PVA  polyvinyl alcohol  PVP  poly(vinylpyrrolidone)  PXRD  powder X-ray diffraction  RESS  rapid expansion of supercritical solutions  RH  relative humidity  SAS  supercritical antisolvent  SAS-EM  supercritical antisolvent enhanced mass transfer  SBA-15  Santa Barbara amorphous type material-15  SCF  supercritical fluid technology  SEM  scanning emission microscopy  SLS  sodium lauryl sulfate  STPP  sodium tripolyphosphate  TEM  transmission emission microscopy  TEOS  tetraethyl orthosilicate  glass transition temperature  THF  tetrahydrofuran  TMAOH  tetramethylammonium hydroxide  TMC  trimethyl chitosan  TPGS  tocopheryl polyethylene glycol succinate  TPP  pentasodium tripolyphosphate  TRPV1  transient receptor potential cation channel subfamily V member 1  USP  United States Pharmacopeia  W/O/W  water in oil in water  YMCR  Y-junction microchannel reactor
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