title: Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process.
abstract: OBJECTIVE
  To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process.
  
  
  METHODS
  Physicochemical stability was performed in accelerated (40°C 70 ± 5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12 mg/kg formulations.
  
  
  RESULTS
  Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2 ± 0.6% at 6 months and 97.9 ± 0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12 mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol® was liver>kidney>lung>brain.
  
  
  CONCLUSIONS
  This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.
authors.affiliation: Pharm. R&D Institute, Hanmi Pharm. Co., Ltd., Hwasung, Gyeonggi 445-913, Republic of Korea.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Shanmugam
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Chi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004356:Drug Storage; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel