Article
Pharmacology & Pharmacy
Xiaofeng Lu, Shreya S. Kulkarni, Hanmin Dong, Yongan Tang, Li Yi, Supriya Gupta
Summary: Low solid content and high fill drug product configuration present challenges for obtaining elegant cake appearance after lyophilization. This study optimized the freezing process to achieve elegant cakes in a narrow primary drying operating space. A Design of Experiment (DoE) approach was used to evaluate the effect of shelf cooling rate and annealing temperature on cake appearance. The slope of product resistance (Rp) vs. dried layer thickness (Ldry) was used as the quantitative response. The optimized freezing process resulted in improved cake appearance and batch homogeneity.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Yingyuan Zhao, Zhaoxuan Wang, Shuxian Liu, Shiying Xie, Yinchun Xie, Ruifang Li, Hiroaki Oda
Summary: This research screens the best ratio of compound lyophilization protectants through single-factor experiments and response surface optimization experiments, and prepares excellent astaxanthin/BSA/chitosan nanosuspension (ABC-NPs) lyophilized powder, solving the problem of inconvenient storage and transportation of aqueous drugs.
Review
Biochemistry & Molecular Biology
Matthew S. Gatto, Wided Najahi-Missaoui
Summary: Nanoparticles have advantages and limitations as drug carriers, and lyophilization can increase their stability and the shelf life of drug products, but improvements are still needed in various aspects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Ivonne Seifert, Alessandro Bregolin, Davide Fissore, Wolfgang Friess
Summary: A study was conducted to investigate the effects of different formulations of arginine with various counter ions on the stability of a monoclonal antibody. It was found that arginine hydrochloride provided the best protein stability at low antibody concentration, followed by arginine succinate, while arginine citrate/phosphate/lactobionate formulations showed inferior protein stability. Addition of sucrose improved cake appearance and protein stability in the formulations. In conclusion, sugar-free arginine hydrochloride and lactobionate lyophilisates demonstrated comparable or better stability than sucrose, with the best protein stability found in mixtures of arginine hydrochloride/lactobionate/succinate with sucrose.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Jijun Wang, James A. Searles, Ekaterina Torres, Serguei A. Tchessalov, Anthony L. Young
Summary: Comparing ice-fog controlled ice nucleation with annealing at the same temperature, the experiment found that ice-fog controlled nucleation had a greater impact on various indicators during the freezing process, including reconstitution time, drying time, cake resistance, specific surface area, and moisture content.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Nicole Haerdter, Raimund Geidobler, Ingo Presser, Gerhard Winter
Summary: Recently, microwave-assisted freeze-drying (MFD) has gained attention for its ability to significantly reduce the drying times of biopharmaceuticals compared to conventional freeze-drying (CFD). This study presents a new technical MFD setup that allows for the retrofitting of standard lyophilizers with microwave modules. Process data was collected to evaluate the speed, settings, and controllability of MFD processes, as well as the quality and stability of monoclonal antibody (mAb) formulations. The findings demonstrate that MFD can drastically shorten drying times, maintain good controllability, and produce stable lyophilizates with an elegant cake appearance.
Article
Medicine, Research & Experimental
Caio H. N. Barros, Manuel Alfaro, Cormac Costello, Fei Wang, Kedar Sapre, Suneel Rastogi, Shivkumar Chiruvolu, James Connolly, Elizabeth M. M. Topp
Summary: The effects of atomic layer (ALC) coating on physical properties and storage stability of solid powders containing myoglobin were investigated. The results showed that ALC coatings can stabilize solid protein formulations during storage, with higher recovery of soluble protein and lower soluble protein aggregate content compared to uncoated samples.
MOLECULAR PHARMACEUTICS
(2023)
Review
Pharmacology & Pharmacy
Seema Thakral, Jayesh Sonje, Bhushan Munjal, Raj Suryanarayanan
Summary: This review provides an overview of the current knowledge on protein stabilization during freezing and freeze-drying processes, focusing on the impact of excipients on protein stability and functionality in frozen and freeze-dried systems.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Eloize Silva Alves, Cintia Stefhany Ripke Ferreira, Paulo Ricardo Souza, Andressa Rafaella Silva Bruni, Matheus Campos Castro, Bruno Henrique Figueiredo Saqueti, Oscar Oliveira Santos, Grasiele Scaramal Madrona, Jesui Vergilio Visentainer
Summary: This study investigated the effects of maltodextrin and gum arabic on freeze-dried human milk (HM), aiming to improve its quality and solubility. The results showed that both coatings led to higher solubility and better stabilization of HM, with gum arabic demonstrating superior performance. The combination of gum arabic and maltodextrin also showed promising results, indicating their potential synergistic effects.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Agricultural Engineering
Karine Modolon Zepon, Caroline do Amaral Fetzner Pucci, Alana Witt Hansen, Fernanda Mendes de Moraes, do Nascimento Jose Heriberto Oliveria, Fernando Dal Pont Morisso, Rachel Faverzani Magnago, Ana Luiza Ziulkoski
Summary: This study proposes using maltose and lactose as reducing and cryoprotectant agents to improve the long-term stability of silver nanoparticles (AgNPs). The sugars can act as reducing and capping agents of the synthesized AgNPs, and prevent aggregation under freezing and freeze-drying. The freeze-dried AgNPs showed more stability and maintained their antibacterial and cytotoxic activities, making maltose and lactose a green alternative for synthesizing and preserving AgNPs.
INDUSTRIAL CROPS AND PRODUCTS
(2023)
Review
Pharmacology & Pharmacy
Emilia Jakubowska, Janina Lulek
Summary: This review discusses the application of lyophilization and its cryogenic modifications in producing solid dispersions and drug nanocrystals, emphasizing freeze-drying as a particle engineering tool. The focus is on the relationships between formulation and process parameters and the properties of the obtained material.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ryo Ohori, Tomomi Akita, Chikamasa Yamashita
Summary: The ramp rate of shelf temperature in the primary drying process has been found to affect final product quality. High concentration disaccharide solutions are more prone to macroscopic collapse at a slow ramp rate. Formulations with mannitol, glycine, and dextran show resistance to drying failure in slow ramp cycles. Additionally, increasing protein concentration can inhibit slow ramp-induced collapse.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Emilia Jakubowska, Michal Bielejewski, Bartlomiej Milanowski, Janina Lulek
Summary: The aim of this study was to investigate the effect of freeze-drying on the particle size of bottom-up processed cilostazol nanosuspension after redispersion. Optimal freeze-drying conditions were identified, and the freeze-dried nanocrystals retained their original size, polymorphic form, and improved dissolution rate.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Agnes Molnar, Tamas Lakat, Adam Hosszu, Beata Szebeni, Anna Balogh, Laszlo Orfi, Attila J. Szabo, Andrea Fekete, Judit Hodrea
Summary: This study provides lyophilization protocols for various rat and mouse tissues, demonstrating the long-term stability of lyophilized samples and the preservation of protein and RNA quality. By concentrating biological solutions and accurately measuring water content, more reliable data sources are provided for research.
Article
Biochemistry & Molecular Biology
Katarzyna Kalahurska, Pawel P. Ziemianski, Wieslaw J. Roth, Barbara Gil
Summary: The liquid exfoliation of MCM-56 zeolite into monolayers and their isolation/reassembly into zeolites with MWW topology was investigated, showing potential for the formation of active catalysts. Dialysis was efficient in removing sodium cations and preserving microporosity, while freeze-drying was effective in maintaining the layer structure. The presence of secondary mesoporosity increased benzyl alcohol conversion in the test reaction.
Article
Chemistry, Medicinal
Puneet Sharma, William J. Kessler, Robin Bogner, Meena Thakur, Michael J. Pikal
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Polymer Science
Tai-Hsi Fan, Ji-Qin Li, Bruna Minatovicz, Elizabeth Soha, Li Sun, Sajal Patel, Bodhisattwa Chaudhuri, Robin Bogner
Article
Chemistry, Medicinal
Arushi Manchanda, Mary S. Kleppe, Robin H. Bogner
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Chemistry, Medicinal
Rui Fang, Robin H. Bogner, Steven L. Nail, Michael J. Pikal
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Chemistry, Medicinal
Shreya S. Kulkarni, Sajal M. Patel, Robin H. Bogner
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Medicine, Research & Experimental
Arushi Manchanda, Na Li, Robin H. Bogner
MOLECULAR PHARMACEUTICS
(2020)
Article
Chemistry, Multidisciplinary
Rui Fang, Wasfy Obeidat, Michael J. Pikal, Robin H. Bogner
PHARMACEUTICAL RESEARCH
(2020)
Article
Pharmacology & Pharmacy
Bruna Minatovicz, Robin Bogner, Bodhisattwa Chaudhuri
Summary: Lowering the freezing temperature and using forced air flow significantly increased the freezing and thawing rates. Loading distance and freezer set temperature had significant impacts on the activity and tetramer retention of LDH.
Article
Pharmacology & Pharmacy
Shreya S. Kulkarni, Sajal M. Patel, Raj Suryanarayanan, Joseph V. Rinella Jr, Robin H. Bogner
Summary: Reconstitution time of lyophilized protein formulations is complex and dependent on various factors. Partially crystalline cakes exhibit better reconstitution characteristics, with the inclusion of crystallizable excipients proving beneficial in speeding up reconstitution.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Petr Kazarin, William Kessler, Emily Gong, Seongkyu Yoon, Huolong Liu, Richard Marx, Robin Bogner, Alina Alexeenko
Summary: This study introduces a compact model for lyophilizer equipment capability, utilizing computational fluid dynamics to reduce experimental workload and discussing key parameters. The compact model deviates from experimental data within 10%, while full CFD simulations are within 5% of the experimental results.
Article
Pharmacology & Pharmacy
Robin Bogner, Emily Gong, William Kessler, Michael Hinds, Arushi Manchanda, Seongkyu Yoon, Huolong Liu, Richard Marx, Jessie Zhao, Puneet Sharma, Akhilesh Bhambhani, Justin Stanbro, Alina Alexeenko, Petr Kazarin
Summary: Freeze-drying is a complex operation that requires careful design and planning. A software tool has been developed to assist in process development and scale-up. Experimental determination of model inputs and use of a primary drying heterogeneous freeze-drying model have been effective in ensuring accuracy of predicted product temperature and drying times.
Article
Pharmacology & Pharmacy
Wei-Chung Luo, Andre O'Reilly Beringhs, Rachel Kim, William Zhang, Sajal M. Patel, Robin H. Bogner, Xiuling Lu
Summary: Freeze-drying is an effective method to enhance the long-term stability of nanomedicines, but different types of nanoparticles face varying challenges during the process. The addition of lyoprotectants can help maintain quality, but its effects differ depending on the type of nanoparticles. The study identified that freeze-drying impacts key characteristics differently for solid lipid nanoparticles, polymeric nanoparticles, and liposomes.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Chemistry, Medicinal
Bruna Minatovicz, Sameera Sansare, Tanu Mehta, Robin H. Bogner, Bodhisattwa Chaudhuri
Summary: This study aimed to determine the individual contributions of freeze-concentration, ice surface area, and processing time to protein destabilization. The ice specific surface area (SSA) was found to increase with an increase in the freezing rate and was also impacted by the position of the sample within the container. The distribution of protein throughout the frozen solution and its stability were enhanced under fast freezing conditions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Lauren Fontana, Carl Anderson, Robin Bogner, Michael Pikal
Summary: Raman scattering is a promising routine tool for detecting secondary and smaller tertiary structural changes in both solutions and solids before aggregation. A new method utilizing principal component analysis (PCA) of Raman spectra successfully detected pH-induced changes in protein structure linked to aggregate formation. The long-term goal is to explore Raman characterization as a routine monitoring tool for protein stability in both solution and solid states.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Pooja Sane, Robin H. Bogner, Bakul Bhatnagar, Serguei Tchessalov
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)