PMID- 29677152
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1996-1944 (Print)
IS  - 1996-1944 (Electronic)
IS  - 1996-1944 (Linking)
VI  - 11
IP  - 4
DP  - 2018 Apr 20
TI  - Optimization of the Critical Parameters of the Spherical Agglomeration 
      Crystallization Method by the Application of the Quality by Design Approach.
LID - 10.3390/ma11040635 [doi]
LID - 635
AB  - This research work presents the use of the Quality by Design (QbD) concept for 
      optimization of the spherical agglomeration crystallization method in the case of 
      the active agent, ambroxol hydrochloride (AMB HCl). AMB HCl spherical crystals 
      were formulated by the spherical agglomeration method, which was applied as an 
      antisolvent technique. Spherical crystals have good flowing properties, which 
      makes the direct compression tableting method applicable. This means that the 
      amount of additives used can be reduced and smaller tablets can be formed. For 
      the risk assessment, LeanQbD Software was used. According to its results, four 
      independent variables (mixing type and time, dT (temperature difference between 
      solvent and antisolvent), and composition (solvent/antisolvent volume ratio)) and 
      three dependent variables (mean particle size, aspect ratio, and roundness) were 
      selected. Based on these, a 2(-)3 mixed-level factorial design was constructed, 
      crystallization was accomplished, and the results were evaluated using Statistica 
      for Windows 13 program. Product assay was performed and it was revealed that 
      improvements in the mean particle size (from ~13 to ~200 µm), roundness 
      (from ~2.4 to ~1.5), aspect ratio (from ~1.7 to ~1.4), and flow properties were 
      observed while polymorphic transitions were avoided.
FAU - Gyulai, Orsolya
AU  - Gyulai O
AUID- ORCID: 0000-0002-5582-4184
AD  - Institute of Pharmaceutical Technology and Regulatory Affairs, University of 
      Szeged, 6720 Szeged, Hungary. gyulai.orsolya@pharm.u-szeged.hu.
FAU - Kovacs, Anita
AU  - Kovacs A
AD  - Institute of Pharmaceutical Technology and Regulatory Affairs, University of 
      Szeged, 6720 Szeged, Hungary. anita.kovacs@pharm.u-szeged.hu.
FAU - Sovany, Tamas
AU  - Sovany T
AUID- ORCID: 0000-0003-3392-7788
AD  - Institute of Pharmaceutical Technology and Regulatory Affairs, University of 
      Szeged, 6720 Szeged, Hungary. t.sovany@pharm.u-szeged.hu.
FAU - Csoka, Ildiko
AU  - Csoka I
AD  - Institute of Pharmaceutical Technology and Regulatory Affairs, University of 
      Szeged, 6720 Szeged, Hungary. csoka@pharm.u-szeged.hu.
FAU - Aigner, Zoltan
AU  - Aigner Z
AD  - Institute of Pharmaceutical Technology and Regulatory Affairs, University of 
      Szeged, 6720 Szeged, Hungary. aigner@pharm.u-szeged.hu.
LA  - eng
PT  - Journal Article
DEP - 20180420
PL  - Switzerland
TA  - Materials (Basel)
JT  - Materials (Basel, Switzerland)
JID - 101555929
PMC - PMC5951519
OTO - NOTNLM
OT  - ambroxol hydrochloride
OT  - factorial design
OT  - powder rheology analysis
OT  - quality by design
OT  - spherical crystallization
OT  - spherical morphology
OT  - statistical analysis
COIS- The authors declare no conflict of interest.
EDAT- 2018/04/21 06:00
MHDA- 2018/04/21 06:01
PMCR- 2018/04/20
CRDT- 2018/04/21 06:00
PHST- 2018/03/26 00:00 [received]
PHST- 2018/04/12 00:00 [revised]
PHST- 2018/04/18 00:00 [accepted]
PHST- 2018/04/21 06:00 [entrez]
PHST- 2018/04/21 06:00 [pubmed]
PHST- 2018/04/21 06:01 [medline]
PHST- 2018/04/20 00:00 [pmc-release]
AID - ma11040635 [pii]
AID - materials-11-00635 [pii]
AID - 10.3390/ma11040635 [doi]
PST - epublish
SO  - Materials (Basel). 2018 Apr 20;11(4):635. doi: 10.3390/ma11040635.