PMID- 31974817
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20200721
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
VI  - 21
IP  - 3
DP  - 2020 Jan 23
TI  - Study of Top-down and Bottom-up Approaches by Using Design of Experiment (DoE) to 
      Produce Meloxicam Nanocrystal Capsules.
PG  - 79
LID - 10.1208/s12249-020-1621-7 [doi]
AB  - In order to investigate the correlation among energy input-related, drug-related, 
      and stabilizer-related aspects for both top-down and bottom-up nanocrystal 
      production, meloxicam nanosuspensions (NS) were produced by using three different 
      methods (low-energy wet milling, high-pressure homogenization, and precipitation) 
      and each method was optimized by using design of experiment (DoE). Box-Behnken 
      design of 3 factors and 3 levels was applied for the optimization of each method. 
      All the three models were found to be significant and the optimized process 
      parameters were used for production of NS, respectively. Interestingly, by 
      comparison of the top-down and bottom-up approaches, the influence of energy 
      input (homogenization pressure or milling speed) from the instruments seemed not 
      significant for top-down compared with bottom-up for this drug. Different 
      mechanisms of homogenization (relatively high energy zone) and milling 
      (relatively low energy zone) led to obtained various significant correlations for 
      each method. Capsules containing nanocrystals were successfully produced by using 
      a novel method applying NS (after wet bead milling and homogenization processes) 
      as wetting agent for direct capsuling and showed superiority regarding as 
      dissolution rate compared with the traditional two-step method (freeze-dried 
      powder used for capsuling as the first step). Different NS preparation 
      methodologies proved to have a direct influence on the following capsuling 
      process and consequently, in the dissolution rate. This study also proved that 
      residual DMSO in nanosuspension after precipitation process could affect the 
      freeze-drying process, which might further alter the redispersion and influence 
      the downstream processes.
FAU - Liu, Tao
AU  - Liu T
AD  - Department of Pharmaceutical Engineering, College of Chemical Engineering, 
      Qingdao University of Science and Technology, Qingdao, China. 
      taoyanghe@hotmail.com.
FAU - Yu, Xinxin
AU  - Yu X
AD  - Department of Pharmaceutical Engineering, College of Chemical Engineering, 
      Qingdao University of Science and Technology, Qingdao, China.
FAU - Yin, Haipeng
AU  - Yin H
AD  - Department of Internal Medicine, Qingdao orthopaedic Hospital, Qingdao, China.
LA  - eng
PT  - Journal Article
DEP - 20200123
PL  - United States
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
RN  - 0 (Capsules)
RN  - 0 (Suspensions)
RN  - VG2QF83CGL (Meloxicam)
SB  - IM
MH  - Capsules
MH  - Meloxicam/*chemistry
MH  - Nanoparticles/chemistry
MH  - Particle Size
MH  - Solubility
MH  - Suspensions
MH  - Technology, Pharmaceutical/*methods
OTO - NOTNLM
OT  - design of experiment (DoE)
OT  - dissolution
OT  - meloxicam
OT  - nanocrystals
EDAT- 2020/01/25 06:00
MHDA- 2020/07/22 06:00
CRDT- 2020/01/25 06:00
PHST- 2019/09/20 00:00 [received]
PHST- 2020/01/06 00:00 [accepted]
PHST- 2020/01/25 06:00 [entrez]
PHST- 2020/01/25 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
AID - 10.1208/s12249-020-1621-7 [pii]
AID - 10.1208/s12249-020-1621-7 [doi]
PST - epublish
SO  - AAPS PharmSciTech. 2020 Jan 23;21(3):79. doi: 10.1208/s12249-020-1621-7.