PMID- 21864663
OWN - NLM
STAT- MEDLINE
DCOM- 20120203
LR  - 20181201
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 419
IP  - 1-2
DP  - 2011 Oct 31
TI  - Thermal processing of a poorly water-soluble drug substance exhibiting a high 
      melting point: the utility of KinetiSol(R) Dispersing.
PG  - 222-30
LID - 10.1016/j.ijpharm.2011.08.007 [doi]
AB  - Poorly water-soluble drug substances that exhibit high melting points are often 
      difficult to successfully process by fusion-based techniques. The purpose of this 
      study was to identify a suitable polymer system for meloxicam (MLX), a high 
      melting point class II BCS compound, and investigate thermal processing 
      techniques for the preparation of chemically stable single phase solid 
      dispersions. Thermal and solution based screening techniques were utilized to 
      screen hydrophilic polymers suitable for immediate release formulations. Results 
      of the screening studies demonstrated that Soluplus((R))(SOL) provided the highest 
      degree of miscibility and solubility enhancement. A hot-melt extrusion 
      feasibility study demonstrated that high temperatures and extended residence 
      times were required in order to render compositions amorphous, causing 
      significant degradation of MLX. A design of experiments (DOE) was conducted on 
      the KinetiSol((R)) Dispersing (KSD) process to evaluate the effect of processing 
      conditions on the chemical stability and amorphous character of MLX. The study 
      demonstrated that ejection temperature significantly impacted MLX stability. All 
      samples prepared by KSD were substantially amorphous. Dissolution analysis of the 
      KSD processed solid dispersions showed increased dissolution rates and extent of 
      supersaturation over the marketed generic MLX tablets.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Hughey, Justin R
AU  - Hughey JR
AD  - Division of Pharmaceutics, The University of Texas at Austin, 1 University 
      Station A1920, Austin, TX 78712, USA. justinhughey@utexas.edu
FAU - Keen, Justin M
AU  - Keen JM
FAU - Brough, Chris
AU  - Brough C
FAU - Saeger, Sophie
AU  - Saeger S
FAU - McGinity, James W
AU  - McGinity JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110816
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Drug Carriers)
RN  - 0 (Polymers)
RN  - 0 (Tablets)
RN  - 0 (Thiazines)
RN  - 0 (Thiazoles)
RN  - 059QF0KO0R (Water)
RN  - VG2QF83CGL (Meloxicam)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/chemistry
MH  - Drug Carriers/*chemistry
MH  - Drug Stability
MH  - Feasibility Studies
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Meloxicam
MH  - Polymers/*chemistry
MH  - Solubility
MH  - Tablets
MH  - Temperature
MH  - Thiazines/*administration & dosage/chemistry
MH  - Thiazoles/*administration & dosage/chemistry
MH  - Time Factors
MH  - Transition Temperature
MH  - Water/chemistry
EDAT- 2011/08/26 06:00
MHDA- 2012/02/04 06:00
CRDT- 2011/08/26 06:00
PHST- 2011/03/07 00:00 [received]
PHST- 2011/06/20 00:00 [revised]
PHST- 2011/08/08 00:00 [accepted]
PHST- 2011/08/26 06:00 [entrez]
PHST- 2011/08/26 06:00 [pubmed]
PHST- 2012/02/04 06:00 [medline]
AID - S0378-5173(11)00769-1 [pii]
AID - 10.1016/j.ijpharm.2011.08.007 [doi]
PST - ppublish
SO  - Int J Pharm. 2011 Oct 31;419(1-2):222-30. doi: 10.1016/j.ijpharm.2011.08.007. 
      Epub 2011 Aug 16.