PMID- 22162657
OWN - NLM
STAT- MEDLINE
DCOM- 20120621
LR  - 20211021
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 6
DP  - 2011
TI  - Enhanced bioavailability of sirolimus via preparation of solid dispersion 
      nanoparticles using a supercritical antisolvent process.
PG  - 2997-3009
LID - 10.2147/IJN.S26546 [doi]
AB  - BACKGROUND: The aim of this study was to improve the physicochemical properties 
      and bioavailability of poorly water-soluble sirolimus via preparation of a solid 
      dispersion of nanoparticles using a supercritical antisolvent (SAS) process. 
      METHODS: First, excipients for enhancing the stability and solubility of 
      sirolimus were screened. Second, using the SAS process, solid dispersions of 
      sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or 
      without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene 
      glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle 
      size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. 
      Solid state characterization, kinetic solubility, powder dissolution, stability, 
      and pharmacokinetics were analyzed in rats. RESULTS: X-ray diffraction, 
      differential scanning calorimetry, and high-pressure liquid chromatography 
      indicated that sirolimus existed in an anhydrous amorphous form within a solid 
      dispersion of nanoparticles and that no degradation occurred after SAS 
      processing. The improved supersaturation and dissolution of sirolimus as a solid 
      dispersion of nanoparticles appeared to be well correlated with enhanced 
      bioavailability of oral sirolimus in rats. With oral administration of a solid 
      dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and 
      AUC(0-->12h) of sirolimus were increased by approximately 18.3-fold and 15.2-fold, 
      respectively. CONCLUSION: The results of this study suggest that preparation of 
      PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a 
      promising approach for improving the bioavailability of sirolimus.
FAU - Kim, Min-Soo
AU  - Kim MS
AD  - College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
FAU - Kim, Jeong-Soo
AU  - Kim JS
FAU - Park, Hee Jun
AU  - Park HJ
FAU - Cho, Won Kyung
AU  - Cho WK
FAU - Cha, Kwang-Ho
AU  - Cha KH
FAU - Hwang, Sung-Joo
AU  - Hwang SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111124
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
RN  - 0 (Drug Carriers)
RN  - 0 (Surface-Active Agents)
RN  - FZ989GH94E (Povidone)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Administration, Oral
MH  - Analysis of Variance
MH  - Animals
MH  - Area Under Curve
MH  - Biological Availability
MH  - Drug Carriers/administration & dosage/chemistry/pharmacokinetics
MH  - Drug Stability
MH  - Male
MH  - Nanoparticles/*chemistry
MH  - Nanotechnology/*methods
MH  - Povidone/chemistry
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sirolimus/administration & dosage/chemistry/*pharmacokinetics
MH  - Solubility
MH  - Surface-Active Agents/chemistry
PMC - PMC3230567
OTO - NOTNLM
OT  - bioavailability
OT  - nanoparticles
OT  - sirolimus
OT  - solubility
OT  - supercritical antisolvent
EDAT- 2011/12/14 06:00
MHDA- 2012/06/22 06:00
PMCR- 2011/11/24
CRDT- 2011/12/14 06:00
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/06/22 06:00 [medline]
PHST- 2011/11/24 00:00 [pmc-release]
AID - ijn-6-2997 [pii]
AID - 10.2147/IJN.S26546 [doi]
PST - ppublish
SO  - Int J Nanomedicine. 2011;6:2997-3009. doi: 10.2147/IJN.S26546. Epub 2011 Nov 24.