PMID- 33686561
OWN - NLM
STAT- MEDLINE
DCOM- 20211108
LR  - 20240401
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 38
IP  - 4
DP  - 2021 Apr
TI  - Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design 
      Space Determination of Freeze-Drying Processes.
PG  - 707-719
LID - 10.1007/s11095-021-03023-x [doi]
AB  - PURPOSE: Present (i) an infrared (IR)-based Process Analytical Technology (PAT) 
      installed in a lab-scale freeze-dryer and (ii) a micro freeze-dryer (MicroFD(R)) as 
      effective tools for freeze-drying design space calculation of the primary drying 
      stage. METHODS: The case studies investigated are the freeze-drying of a 
      crystalline (5% mannitol) and of an amorphous (5% sucrose) solution processed in 
      6R vials. The heat (K(v)) and the mass (R(p)) transfer coefficients were 
      estimated: tests at 8, 13 and 26 Pa were carried out to assess the chamber 
      pressure effect on K(v). The design space of the primary drying stage was 
      calculated using these parameters and a well-established model-based approach. 
      The results obtained using the proposed tools were compared to the ones in case 
      K(v) and R(p) were estimated in a lab-scale unit through gravimetric tests and a 
      thermocouple-based method, respectively. RESULTS: The IR-based method allows a 
      non-gravimetric estimation of the K(v) values while with the micro freeze-dryer 
      gravimetric tests require a very small number of vials. In both cases, the 
      obtained values of K(v) and R(p), as well as the resulting design spaces, were 
      all in very good agreement with those obtained in a lab-scale unit through the 
      gravimetric tests (K(v)) and the thermocouple-based method (R(p)). CONCLUSIONS: 
      The proposed tools can be effectively used for design space calculation in 
      substitution of other well-spread methods. Their advantages are mainly the less 
      laborious K(v) estimation process and, as far as the MicroFD(R) is concerned, the 
      possibility of saving time and formulation material when evaluating R(p).
FAU - Harguindeguy, Maite
AU  - Harguindeguy M
AUID- ORCID: 0000-0001-7373-277X
AD  - Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca 
      degli Abruzzi 24, 10129, Torino, Italy. maite.harguindeguy@polito.it.
FAU - Fissore, Davide
AU  - Fissore D
AD  - Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca 
      degli Abruzzi 24, 10129, Torino, Italy.
LA  - eng
PT  - Journal Article
DEP - 20210308
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 3OWL53L36A (Mannitol)
RN  - 57-50-1 (Sucrose)
SB  - IM
MH  - Chemistry, Pharmaceutical
MH  - Computer-Aided Design/*instrumentation
MH  - Drug Compounding/instrumentation/*methods
MH  - Freeze Drying/instrumentation/*methods
MH  - Mannitol/chemistry
MH  - *Models, Chemical
MH  - Spectrophotometry, Infrared/instrumentation/methods
MH  - Sucrose/chemistry
PMC - PMC8057969
OTO - NOTNLM
OT  - Design space
OT  - freeze-drying process design/optimization
OT  - heat and mass transfer
OT  - mechanistic approach
OT  - model parameters
OT  - primary drying
EDAT- 2021/03/10 06:00
MHDA- 2021/11/09 06:00
PMCR- 2021/03/08
CRDT- 2021/03/09 06:15
PHST- 2020/11/17 00:00 [received]
PHST- 2021/02/23 00:00 [accepted]
PHST- 2021/03/10 06:00 [pubmed]
PHST- 2021/11/09 06:00 [medline]
PHST- 2021/03/09 06:15 [entrez]
PHST- 2021/03/08 00:00 [pmc-release]
AID - 10.1007/s11095-021-03023-x [pii]
AID - 3023 [pii]
AID - 10.1007/s11095-021-03023-x [doi]
PST - ppublish
SO  - Pharm Res. 2021 Apr;38(4):707-719. doi: 10.1007/s11095-021-03023-x. Epub 2021 Mar 
      8.