Representative Scale-Down Lyophilization Cycle Development Using a Seven-Vial Freeze-Dryer (MicroFD®)

Goldman, Johnathan M.; Chen, Xiao; Register, Jeffrey T.; Nesarikar, Vishwas V.; Iyer, Lavanya K.; Wu, Yongmei; Mugheirbi, Naila A.; Rowe, Jasmine

doi:10.1016/j.xphs.2018.11.018

Cited by 17 publications

(11 citation statements)

References 35 publications

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“…(1) If we carry out a gravimetric test in the micro freeze-dryer to get K v , using ring temperature offset in the range À1 C to À5 C, the value we obtain is close to the mean value of a larger-scale unit; (2) If we carry out also a test in the pilot-and commercial-scale unit to get the value of K v , it is possible to tune the ring temperature offset in the micro freeze-dryer to replicate with higher accuracy the product dynamics. This issue was discussed in the study by Goldman et al 27 and, thus, is not further discussed here.…”

Section: Determination Of Model Parameters K V and R Pmentioning

confidence: 89%

“…A different system was proposed by Thompson et al 26 and investigated by Goldman et al 27 and by Fissore et al 28 This device (MicroFD®) uses a completely different approach to get uniformity (of temperature and drying rate) in the small-scale batch, minimizing (and even canceling) the edge effect. In this system, the batch of vials is surrounded by an aluminum ring in contact with the external vials of the batch.…”

Section: Introductionmentioning

confidence: 99%

“…In this system, the batch of vials is surrounded by an aluminum ring in contact with the external vials of the batch. Removable thermal conductors are used to arrange different types of vials, for example, 20 R vials, 27 6 R vials 28 and others, to ensure the contact between the edge vials and this external ring system. The goal of this ring is to mimic the presence of an additional row of vials where sublimation is occurring, in such a way that the edge vials of the small-scale batch will behave as central vials of a larger batch.…”

Section: Introductionmentioning

confidence: 99%

“…In the present configuration of the micro freeze-dryer, a control system acts to maintain a constant offset temperature between the ring and the product (defined as the difference between the temperature of the ring and that of the product in the vials). Goldman et al 27 considered a batch of 7 (20 mL) vials and pointed out that it was possible to reproduce in the micro freeze-dryer the drying conditions of the edge or of the central vials of a pilot-scale unit. Fissore et al 28 considered a batch of 19 (10 mL) vials, evidencing the role of the ring in obtaining uniform drying conditions in the micro freeze-dryer.…”

Section: Introductionmentioning

confidence: 99%

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Development of Freeze-Drying Cycles for Pharmaceutical Products Using a Micro Freeze-Dryer

Fissore

Harguindeguy

Ramirez

et al. 2020

Journal of Pharmaceutical Sciences

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This article aims to investigate how a small-scale freeze-dryer can be used for process design. The system encompasses a temperature controlled metallic ring that surrounds a small batch of vials, in contact with the external vials through removable thermal conductors. The temperature of the ring can be modified to keep a constant difference with the temperature of one or more vials of the batch. In this article, an extensive validation of the system is given, considering 10% w/w sucrose and 5% w/w mannitol solutions, processed in different types of vials (6 R and 20 R) and in different operating conditions. The micro freezedryer was also shown to be able to provide accurate estimates of the overall heat transfer coefficient from the shelf to the product in the vials (K v) and of the resistance of the dried cake to vapor flux (R p): both values appeared to be very close to those obtained for the same case studies in a pilot-scale unit. Finally, the use of the micro freeze-dryer to control product temperature and drying time values to simulate a pilot-scale unit was addressed, thus demonstrating the adequacy of this system for process scaleup.

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Section: Determination Of Model Parameters K V and R Pmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of Freeze-Drying Cycles for Pharmaceutical Products Using a Micro Freeze-Dryer

Fissore

Harguindeguy

Ramirez

et al. 2020

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…radiation from chamber walls and door (19), while gravimetric test provides a very detailed picture of the system. As far as R p is concerned, it may be estimated as well as by means of PRT-based algorithms (23,28), through TDLAS (29), or using the product temperature measurement in a run (30).…”

Section: Introductionmentioning

confidence: 99%

Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes

Harguindeguy

Fissore

2021

Pharm Res

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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®) 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 (Kv) and the mass (Rp) transfer coefficients were estimated: tests at 8, 13 and 26 Pa were carried out to assess the chamber pressure effect on Kv. 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 Kv and Rp 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 Kv values while with the micro freeze-dryer gravimetric tests require a very small number of vials. In both cases, the obtained values of Kv and Rp, 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 (Kv) and the thermocouple-based method (Rp). 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 Kv estimation process and, as far as the MicroFD® is concerned, the possibility of saving time and formulation material when evaluating Rp.

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Advances in Freeze Drying of Biologics and Future Challenges and Opportunities

Bhatnagar

Tchessalov

2020

Drying Technologies for Biotechnology and Pharmaceutical Applications

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Representative Scale-Down Lyophilization Cycle Development Using a Seven-Vial Freeze-Dryer (MicroFD®)

Cited by 17 publications

References 35 publications

Development of Freeze-Drying Cycles for Pharmaceutical Products Using a Micro Freeze-Dryer

Development of Freeze-Drying Cycles for Pharmaceutical Products Using a Micro Freeze-Dryer

Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes

Advances in Freeze Drying of Biologics and Future Challenges and Opportunities

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