PMID- 21774741
OWN - NLM
STAT- MEDLINE
DCOM- 20120416
LR  - 20161125
IS  - 1520-5762 (Electronic)
IS  - 0363-9045 (Linking)
VI  - 38
IP  - 2
DP  - 2012 Feb
TI  - Use of highly compressible Ceolus microcrystalline cellulose for improved dosage 
      form properties containing a hydrophilic solid dispersion.
PG  - 180-9
LID - 10.3109/03639045.2011.595415 [doi]
AB  - The development of amorphous solid dispersions containing poorly soluble drug 
      substances has been well-documented; however, little attention has been given to 
      the development of the finished dosage form. The objective of this study was to 
      investigate the use of Ceolus() microcrystalline cellulose, a highly 
      compressible excipient, for the production of rapidly disintegrating tablets 
      containing a hydrophilic solid dispersion of a poorly soluble drug, indomethacin. 
      Solid dispersions of indomethacin and Kollidon((R)) VA64 were prepared by hot melt 
      extrusion and characterized for amorphous nature. Milled dispersion particles at 
      500 mg/g drug loading were shown to be amorphous by differential scanning 
      calorimetry and provided rapid dissolution in sink conditions. Physical 
      characterization of the milled extrudate showed that the particle size of the 
      intermediate was comparable with Ceolus() PH-102 and larger than the high 
      compressibility grades of microcrystalline cellulose selected for the trial 
      (Ceolus() KG-802, Ceolus() UF-711). Preliminary tableting trials showed that 
      dissolution performance was significantly reduced for formulations at dispersion 
      loadings in excess of 50%. Using a mixture design of experiments (DOE), the 
      levels of PH-102, KG-802, UF-711, and PH-301 were optimized. Trials revealed a 
      synergistic relationship between conventional grades (PH-102 and PH-301) and 
      highly compressible grades (KG-802 and UF-711) leading to improved compression 
      characteristics and more rapid dissolution rates. The formulation and resulting 
      compressibility were also shown to have an impact on in vitro supersaturation 
      indicating tablet formulation could impact oral bioavailability. Through the use 
      of highly compressible microcrystalline cellulose grades such as Ceolus() KG-802 
      and UF-711, it may be possible to maximize the bioavailability benefit of 
      amorphous solid dispersions administered as tablet dosage forms.
FAU - Dinunzio, James C
AU  - Dinunzio JC
AD  - Drug Dynamics Institute, The University of Texas at Austin, Austin, TX, USA. 
      james.dinunzio@roche.com
FAU - Schilling, Sandra U
AU  - Schilling SU
FAU - Coney, Andrew W
AU  - Coney AW
FAU - Hughey, Justin R
AU  - Hughey JR
FAU - Kaneko, Nobuya
AU  - Kaneko N
FAU - McGinity, James W
AU  - McGinity JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110721
PL  - England
TA  - Drug Dev Ind Pharm
JT  - Drug development and industrial pharmacy
JID - 7802620
RN  - 0 (Excipients)
RN  - 9004-34-6 (Cellulose)
RN  - OP1R32D61U (microcrystalline cellulose)
SB  - IM
MH  - Analysis of Variance
MH  - Biological Availability
MH  - Cellulose/*chemistry
MH  - Drug Compounding/*methods
MH  - Excipients/*chemistry
MH  - Hot Temperature
MH  - *Hydrophobic and Hydrophilic Interactions
MH  - Particle Size
MH  - Solubility
EDAT- 2011/07/22 06:00
MHDA- 2012/04/17 06:00
CRDT- 2011/07/22 06:00
PHST- 2011/07/22 06:00 [entrez]
PHST- 2011/07/22 06:00 [pubmed]
PHST- 2012/04/17 06:00 [medline]
AID - 10.3109/03639045.2011.595415 [doi]
PST - ppublish
SO  - Drug Dev Ind Pharm. 2012 Feb;38(2):180-9. doi: 10.3109/03639045.2011.595415. Epub 
      2011 Jul 21.