Freeze-drying revolution: unleashing the potential of lyophilization in advancing drug delivery systems.

Publisher: Springer Country of Publication: United States NLM ID: 101540061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2190-3948 (Electronic) Linking ISSN: 2190393X NLM ISO Abbreviation: Drug Deliv Transl Res Subsets: MEDLINE

Original Publication: New York : Springer

Drug Delivery Systems* ; Nanoparticles*/chemistry; Freeze Drying/methods ; Drug Stability

Lyophilization also known as freeze-drying is a technique that has been employed to enhance the long-term durability of nanoparticles (NPs) that are utilized for drug delivery applications. This method is used to prevent their instability in suspension. However, this dehydration process can cause stress to the NPs, which can be alleviated by the incorporation of excipients like cryoprotectants and lyoprotectants. Nevertheless, the freeze-drying of NPs is often based on empirical principles without considering the physical-chemical properties of the formulations and the engineering principles of freeze-drying. For this reason, it is crucial to optimize the formulations and the freeze-drying cycle to obtain a good lyophilizate and ensure the preservation of NPs stability. Moreover, proper characterization of the lyophilizate and NPs is of utmost importance in achieving these goals. This review aims to update the recent advancements, including innovative formulations and novel approaches, contributing to the progress in this field, to obtain the maximum stability of formulations. Additionally, we critically analyze the limitations of lyophilization and discuss potential future directions. It addresses the challenges faced by researchers and suggests avenues for further research to overcome these limitations. In conclusion, this review is a valuable contribution to the understanding of the parameters involved in the freeze-drying of NPs. It will definitely aid future studies in obtaining lyophilized NPs with good quality and enhanced drug delivery and therapeutic benefits.
(© 2023. Controlled Release Society.)

Chen Y, Mutukuri TT, Wilson NE, Zhou QT. Pharmaceutical protein solids: drying technology, solid-state characterization and stability. Adv Drug Deliv Rev. 2021;172:211–33. https://doi.org/10.1016/J.ADDR.2021.02.016 .
Varshney D, Shing M. History of lyophilization. In: Varshney D, Singh M, editors. Lyophilized biologics and vaccines. New York: Springer Science; 2015. p. 3–10. https://doi.org/10.1007/978-1-4939-2383-0_1 . (PMID: 10.1007/978-1-4939-2383-0_1)
12 steps of lyophilization history you should know. https://www.lyophilizationworld.com/post/2019/02/06/12-steps-of-lyophilization-history-you-should-know . 2019. Accessed 21 Jun 2023.
Narayana D. Fundamentals and applications of freeze-drying. https://biotecharticles.com/Applications-Article/Fundamentals-and-Applications-of-Freeze-Drying-3557.html . 2016.
Nowak D, Jakubczyk E. The freeze-drying of foods-the characteristic of the process course and the effect of its parameters on the physical properties of food materials. Foods. 2020;9:1488. https://doi.org/10.3390/foods9101488 . (PMID: 10.3390/foods9101488330809837603155)
Roy I, Gupta MN. Freeze-drying of proteins: some emerging concerns. Biotechnol Appl Biochem. 2004;39:165. https://doi.org/10.1042/BA20030133 .
Kasper JC, Winter G, Fries W. Recent advances and further challenges in lyophilization. Eur J Pharm Biopharm. 2013;85:162–9. https://doi.org/10.1016/J.EJPB.2013.05.019 . (PMID: 10.1016/J.EJPB.2013.05.01923751601)
Stratta L, Capozzi LC, Franzino S, Pisano R. Economic analysis of a freeze-drying cycle. Processes. 2020;8(11):1399. https://doi.org/10.3390/pr8111399 . (PMID: 10.3390/pr8111399)
Passot S, Trelea IC, Marin M, Galan M, Morris GJ, Fonseca F. Effect of controlled ice nucleation on primary drying stage and protein recovery in vials cooled in a modified freeze-dryer. J Biomech Eng. 2009;131:074511–6. https://doi.org/10.1115/1.3143034 . (PMID: 10.1115/1.314303419640147)
Liu J, Viverette T, Virgin M, Anderson M, Dalal P. A study of the impact of freezing on the lyophilization of a concentrated formulation with a high fill depth. Pharm Dev Technol. 2005;10:261–72. https://doi.org/10.1081/PDT-54452 . (PMID: 10.1081/PDT-5445215926675)
Searles JA. Freezing and annealing phenomena in lyophilization. In: Rey L, May JC, editors. Freeze drying/lyophilization of pharmaceutical and biological products. London: Informa Healthcare; 2010. p. 52–81.
Pharmaceutical CGMPS for the 21st century-a risk-based approach final report. 2004.
Lee SH, Kim JK, Jee JP, Jang DJ, Park YJ, Kim JE. Quality by design (QbD) application for the pharmaceutical development process. J Pharm Investig. 2022;52(6):649–82. https://doi.org/10.1007/s40005-022-00575-x . (PMID: 10.1007/s40005-022-00575-x)
Recent advances in process optimization of vacuum freeze-drying. American pharmaceutical review - the review of American pharmaceutical business & technology, (n.d.); 2023. https://www.americanpharmaceuticalreview.com/Featured-Articles/160258-Recent-Advances-in-Process-Optimization-of-Vacuum-Freeze-Drying/ .
Applying quality by design to lyophilization. BioPharm Int. 2012;25.  https://www.biopharminternational.com/view/applying-quality-design-lyophilization . Accessed 21 Jun 2023.
Jiang X, Kazarin P, Sinanis MD, Darwish A, Raghunathan N, Alexeenko A, et al. A non-invasive multipoint product temperature measurement for pharmaceutical lyophilization. Sci Reports. 2022;121:1–16. https://doi.org/10.1038/s41598-022-16073-x . (PMID: 10.1038/s41598-022-16073-x)
Schneid S, Gieseler H. Evaluation of a new wireless temperature remote interrogation system (TEMPRIS) to measure product temperature during freeze drying. AAPS PharmSciTech. 2008;9:729–39. https://doi.org/10.1208/S12249-008-9099-8 . (PMID: 10.1208/S12249-008-9099-8185610302977010)
Kasper JC, Wiggenhorn M, Resch M, Friess W. Implementation and evaluation of an optical fiber system as novel process monitoring tool during lyophilization. Eur J Pharm Biopharm. 2013;83:449–59. https://doi.org/10.1016/J.EJPB.2012.10.009 . (PMID: 10.1016/J.EJPB.2012.10.00923159708)
Temperature measurement in lyophilization with Tempris sensors.  https://www.lyophilizationworld.com/post/2020/02/02/temperature-measurement-in-lyophilization-with-tempris-sensors . Accessed 21 Jun 2023.
Patel SM, Pikal MJ. Freeze-drying in novel container system: characterization of heat and mass transfer in glass syringes. J Pharm Sci. 2010;99(7):3188–204.  https://doi.org/10.1002/jps.22086 . Accessed 21 Jun 2023.
DeGrazio FL. Closure and container considerations in lyophilization. In: Rey L, May JC, editors. Freeze drying/ lyophilization of pharmaceutical and biological products. London: Informa Healthcare; 2010. p. 396–412.
Cullen S, Walsh E, Gervasi V, Khamar D, McCoy TR. Technical transfer and commercialisation of lyophilised biopharmaceuticals — application of lyophiliser characterization and comparability. AAPS Open. 2022;81:1–20. https://doi.org/10.1186/S41120-022-00059-0 . (PMID: 10.1186/S41120-022-00059-0)
Koganti VR, Shalaev EY, Berry MR, Osterberg T, Youssef M, Hiebert DN, et al. Investigation of design space for freeze-drying: use of modeling for primary drying segment of a freeze-drying cycle. AAPS PharmSciTech. 2011;12:854–61. https://doi.org/10.1208/S12249-011-9645-7 . (PMID: 10.1208/S12249-011-9645-7217103353167267)
Juckers A, Knerr P, Harms F, Strube J. Emerging PAT for freeze-drying processes for advanced process control. Process. 2022;10:2059. https://doi.org/10.3390/PR10102059 . (PMID: 10.3390/PR10102059)
Alkeev N, Averin S, Son Gratowski S. New method for monitoring the process of freeze drying of biological materials. AAPS PharmSciTech. 2051;16:1474–79. https://doi.org/10.1208/S12249-015-0341-X .
Adali MB, Barresi AA, Boccardo G, Pisano R. Spray freeze-drying as a solution to continuous manufacturing of pharmaceutical products in bulk. Process. 2020;8: 709709. https://doi.org/10.3390/PR8060709 . (PMID: 10.3390/PR8060709)
Henning Gieseler SN, Michael JP, Yves M, Steiner M. Applying quality by design to lyophilization. BioPharm Int. 2012;25.
Freeze-drying market - global forecast to 2025 | MarketsandMarkets, (n.d.). https://www.marketsandmarkets.com/Market-Reports/freeze-drying-lyophilization-equipment-market-24018886.html . Accessed 21 Jun 2023.
Utpal Kumar D, Ranjit B, Ganguly S. Freeze-drying technique and its wide application in biomedical and pharmaceutical sciences. Res J Chem Environ Sci. 2014;2(3):01–4.
Kunal AG, Mallinath H, Deepak B, Pallavi SN. Lyophilization / freeze drying – a review. W J Pharm Res. 2015;4(8):516–43.
Principle, construction, working, uses, merits and demerits of freeze dryer. Pharmaguideline.  https://www.pharmaguideline.com/2007/02/principle-construction-working-uses-merits-demerits-of-freeze-dryers.html .
Freeze dryer - how it works? https://www.solnpharma.com/2022/03/freeze-dryer-how-it-works.html .
Manifold freeze dryers – an overview of their use, limitations and some helpful hints. https://www.millrocktech.com/wp-content/uploads/2017/04/Tech-Note-Manifold-freeze-dryers-An-overview-of-Their-Use-Limitations-and-Some-Helpful-Hints.pdf .
Freeze drying market size, analysis, trends and forecast. https://straitsresearch.com/report/freeze-drying-market .
Rhieu SY, Anderson DD, Janoria K. A regulatory perspective on manufacturing processes pertaining to lyophilized injectable products. AAPS J. 2020;22:1–8. https://doi.org/10.1208/s12248-020-00477-6 . (PMID: 10.1208/s12248-020-00477-6)
Janoria K. Current regulatory considerations on pharmaceutical lyophilization. (nd). www.fda.gov .
Tundisi LL, Ataide JA, Costa JS, Coêlho DF, Liszbinski RB, Lopes AM, et al. Nanotechnology as a tool to overcome macromolecules delivery issues. Colloids Surf. B. 2022;113043.
Chaloner-Larsson G, Bioconsult G, Anderson OR, Antonio Da Fonseca M, Filho C, Gomez Herrera JF. A WHO guide to good manufacturing practice (GMP) requirements. http://apps.who.int/iris/bitstream/10665/64465/2/WHO_VSQ_97.02.pdf .
FDA 21 CFR Part 11 - 7 tips to ensure compliance. https://www.greenlight.guru/blog/tips-to-comply-with-fda-21-cfr-part-11 . 21 Jun 2023.
Part 11, Electronic Records; Electronic signatures - scope and application, guidance for industry. 2003. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/part-11-electronic-records-electronic-signatures-scope-and-application .
Molnar A, Lakat T, Hosszu ASzebeni B, Balogh A, Orfi L, et al. Lyophilization and homogenization of biological samples improves reproducibility and reduces standard deviation in molecular biology techniques. Amino Acids. 2021;53:917–28. https://doi.org/10.1007/S00726-021-02994-W . (PMID: 10.1007/S00726-021-02994-W340022788128086)
Bisht D, Iqbal Z. Lyophilization - process and optimization for pharmaceuticals. Int J Drug Regul Aff. 2018;3:30–40. https://doi.org/10.22270/IJDRA.V3I1.156 .
How COVID-19 affected the freeze-drying industry and what was learned. https://www.labmate-online.com/news/laboratory-products/3/biopharma-process-systems-btl/how-covid-19-affected-the-freeze-drying-industry-and-what-was-learned/54980 .
Lyophilization market outlook (2022–2032).  https://www.factmr.com/report/lyophilization-market . Accessed 3 Oct 2023.
Lyophilization market size, share & growth report 2032.  https://www.factmr.com/report/lyophilization-market . Accessed 21 Jun 2023.
Lyophilized product market size, trends and forecast to 2028.  https://www.coherentmarketinsights.com/market-insight/lyophilized-product-market-4910 . Accessed 21 Jun 2023.
Straif-Bourgeois S, Ratard R, Kretzschmar M. Infectious disease epidemiology. Handb. Epidemiol. 2014:2041. https://doi.org/10.1007/978-0-387-09834-0_34 .
Top 10 companies in the freeze dried technology market. https://www.reportsanddata.com/blog/top-10-companies-in-the-freeze-dried-technology-market . Accessed 21 Jun 2023.
Lyophilization of pharmaceuticals: an overview | LLS Health CDMO. https://lubrizolcdmo.com/blog/lyophilization-of-pharmaceuticals-an-overview/ . Accessed 21 Jun 2023.
AmBisome ^® - Package insert. USFDA.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/050740Orig1s033lbl.pdf . Accessed 21 Jun 2023.
Acetazolamide sodium- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205358Orig1s000lbl.pdf . Accessed 21 Jun 2023.
Zithromax- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/050733Orig1s049lbl.pdf . Accessed 21 Jun 2023.
PROTONIX ^® I.V.- Package insert. USFDA.  https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20988_Protonix . Accessed 21 Jun 2023.
Zyprexa- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf . Accessed 21 Jun 2023.
Eligard ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021731s005,021488s010,021379s010,021343s015lbl.pdf . Accessed 21 Jun 2023.
Advate ^® - Package insert. USFDA. https://www.fda.gov/media/70008/download . Accessed 21 Jun 2023.
Vfend ^® - Package insert. USFDA.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021266s032lbl.pdf . Accessed 21 Jun 2023.
CYTOVENE ^® -IV- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019661s036lbl.pdf . Accessed 21 Jun 2023.
Alimta- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021462s015lbl.pdf . Accessed 21 Jun 2023.
Velcade- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf . Accessed 21 Jun 2023.
Vidaza- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/050974s034lbl.pdf . Accessed 21 Jun 2023.
Abraxane ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021660s047lbl.pdf . Accessed 21 Jun 2023.
Kyprolis ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202714s025lbl.pdf . Accessed 21 Jun 2023.
Merrem ^® IV- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050706s037lbl.pdf . Accessed 21 Jun 2023.
Herceptin ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.pdf . Accessed 21 Jun 2023.
BOTOX- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103000s5232lbl.pdf .
Orencia- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125118s171lbl.pdf . Accessed 21 Jun 2023.
Avonex- Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103628s5189lbl.pdf . Accessed 21 Jun 2023.
Remicade ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103772s5359lbl.pdf . Accessed 21 Jun 2023.
Xolair ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf . Accessed 21 Jun 2023.
Keytruda ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125514s066lbl.pdf . Accessed 21 Jun 2023.
Cosentyx ^® - Package insert. USFDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125504s043lbl.pdf . Accessed 21 Jun 2023.
Kumar N, Jha A. Temperature excursion management: a novel approach of quality system in pharmaceutical industry. Saudi Pharm J. 2017;25(2):176–83. https://doi.org/10.1016/j.jsps.2016.07.001 . (PMID: 10.1016/j.jsps.2016.07.00128344467)
Jain K, Salamat-Miller N, Taylor K. Freeze-thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics. Sci Rep. 2021;11:11332. https://doi.org/10.1038/S41598-021-90772-9 . (PMID: 10.1038/S41598-021-90772-9340597168166975)
Authelin JR, Rodrigues MA, Tchessalov S, Singh SK, McCoy T, et al. Freezing of biologicals revisited: scale, stability, excipients, and degradation stresses. J Pharm Sci. 2020;109:44–61. https://doi.org/10.1016/J.XPHS.2019.10.062 . (PMID: 10.1016/J.XPHS.2019.10.06231705870)
Singh S, Kolhe P, Wang W, Nema S. Large-scale freezing of biologics: a practitioner’s review, part 2: Practical advice. Bioprocess Int. 2009;7:34–42.
Bhatnagar BS, Bogner RH, Pikal MJ. Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm Dev Technol. 207;12:505–23. https://doi.org/10.1080/10837450701481157 .
Evaluating Freeze-Thaw Processes in Biopharmaceutical development: small scale study design.  https://www.sartorius.com/download/692844/bioprocess-int-freeze-thaw-processes-publication-en-jan-2015-1--data.pdf .
Rathore N, Rajan RS. Current perspectives on stability of protein drug products during formulation, fill and finish operations. Biotechnol Prog. 2008;24:504–14. https://doi.org/10.1021/BP070462H . (PMID: 10.1021/BP070462H18484778)
Padala C, Jameel F, Rathore N, Gupta K, Sethuraman A. Impact of uncontrolled vs controlled rate freeze-thaw technologies on process performance and product quality. PDA J Pharm Sci Technol. 2010;64(4):290–8. (PMID: 21502029)
Evaluating freeze/thaw processes in drug manufacturing. https://www.sartorius.com/en/knowledge/science-snippets/evaluating-freeze-thaw-processes-in-drug-manufacturing-701196 . Accessed 22 Jun 2023.
Awotwe-Otoo D, Khan M. Lyophilization of biologics: an FDA perspective. In: Varshney D, Singh M, editors. Lyophilized biologics and vaccines. Springer, New York, NY; 2015. https://doi.org/10.1007/978-1-4939-2383-0_15 . (PMID: 10.1007/978-1-4939-2383-0_15)
Ozgyin L, Horvath A, Balint BL. Lyophilized human cells stored at room temperature preserve multiple RNA species at excellent quality for RNA sequencing. Oncotarget. 2018;9(59):31312–29. https://doi.org/10.18632/oncotarget.25764 . (PMID: 10.18632/oncotarget.25764301403726101130)
Nkenyi R, Pak GD, Tonga C, et al. A retrospective review of vaccine wastage and associated risk factors in the Littoral region of Cameroon during 2016–2017. BMC Public Health. 2022;22:1956. https://doi.org/10.1186/s12889-022-14328-w . (PMID: 10.1186/s12889-022-14328-w362741459590201)
Lyophilization of pharmaceuticals: an overview. https://lubrizolcdmo.com/blog/lyophilization-of-pharmaceuticals-an-overview/ .
Beech KE, Biddlecombe JG, Van Der Walle CF, Stevens LA, Rigby SP, Burley JC, Allen S. Insights into the influence of the cooling profile on the reconstitution times of amorphous lyophilized protein formulations. Eur J Pharm Biopharm. 2015;96:247–54.
Batchelor HK, Marriott JF. Formulations for children: problems and solutions. Br J Clin Pharmacol. 2015;79(3):405–18. https://doi.org/10.1111/bcp.12268 . (PMID: 10.1111/bcp.12268258558224345951)
Hajare AA, More HN. Design of the lyophilization process of a doxorubicin formulation based on thermal properties. Indian J Pharm Sci. 2017;79(6):907–913.
Lim JY, Kim NA, Lim DG, Kim KH, Choi DH, Jeong SH. Process cycle development of freeze drying for therapeutic proteins with stability evaluation. J Pharm Investig. 2016;46. https://doi.org/10.1007/s40005-016-0275-7 .
Challener C. For lyophilization, excipients really do matter. BioPharm International, BioPharm Int. 2017;30(1):32–5. https://www.biopharminternational.com/view/lyophilization-excipients-really-do-matter .
Ionova Y, Wilson L. Biologic excipients: importance of clinical awareness of inactive ingredients. PLoS ONE. 2020;15(6):e0235076. https://doi.org/10.1371/journal.pone.0235076 .
Lale SV, Goyal M, Bansal AK. Development of lyophilization cycle and effect of excipients on the stability of catalase during lyophilization. Int J Pharm Investig. 2011;1(4):214–21. https://doi.org/10.4103/2230-973X.93007 . (PMID: 10.4103/2230-973X.93007230719463465145)
Shah S, Nene S, Rangaraj N, Raghuvanshi RS, Singh SB, Srivastava S. Bridging the gap: academia, industry and FDA convergence for nanomaterials. Drug Dev Ind Pharm. 2020;46(11):1735–46. (PMID: 10.1080/03639045.2020.182105532901536)
Badmus UO, Taggart MA, Boyd KG. The effect of different drying methods on certain nutritionally important chemical constituents in edible brown seaweeds. J Appl Phycol. 2019;31:3883–97. https://doi.org/10.1007/s10811-019-01846-1 . (PMID: 10.1007/s10811-019-01846-1)
Covarrubias CE, Rivera TA, Soto CA, Deeks T, Kalergis AM. Current GMP standards for the production of vaccines and antibodies: an overview. Front Public Health. 2022;3(10):1021905. https://doi.org/10.3389/fpubh.2022.1021905 . (PMID: 10.3389/fpubh.2022.1021905)
Agbozo EY, Dumashie E, Boakye DA, et al. Effects of lyophilization and storage temperature on Wuchereria bancrofti antigen sensitivity and stability. BMC Res Notes. 2018;11:454. https://doi.org/10.1186/s13104-018-3586-0 . (PMID: 10.1186/s13104-018-3586-0299968986042357)
Choi TJ, Jang SP, Jung DS, Lim HM, Byeon YM, Choi IJ. Effect of the freeze-thaw on the suspension stability and thermal conductivity of EG/water-based Al 2 O 3 nanofluids. J Nanomater. 2019. https://doi.org/10.1155/2019/2076341 .
Liu Y, Zhao Y, Feng X. Exergy analysis for a freeze-drying process. 2007. https://doi.org/10.1016/j.applthermaleng.2007.06.004 . (PMID: 10.1016/j.applthermaleng.2007.06.004)
Shukla S. Freeze drying process: a review.  https://doi.org/10.13040/IJPSR.0975-8232.2(12).3061-68 .
Gaidhani KA, Harwalkar M., Bhambere D, Nirgude PS. Lyophilizaton/freeze drying a review. World J Pharm Res. 2015;516–43.
Connolly BD, Le L, Patapoff TW, Cromwell MEM, Moore JMR, Lam P. Protein aggregation in frozen trehalose formulations: effects of composition, cooling rate, and storage temperature. J Pharm Sci. 2015;104:4170–84. https://doi.org/10.1002/JPS.24646 . (PMID: 10.1002/JPS.2464626398200)
Bano G, De-luca R, Tomba E, Marcelli A, Bezzo F, Barolo M. Primary drying optimization in pharmaceutical freeze-drying: a multivial stochastic modeling framework. Ind Eng Chem Res. 2020;59:5056–71. https://doi.org/10.1021/acs.iecr.9b06402 . (PMID: 10.1021/acs.iecr.9b06402)
Assegehegn G, Brito-de la Fuente E, Franco JM, Gallegos C. The importance of understanding the freezing step and its impact on freeze-drying process performance. J Pharm Sci. 2019;108:1378–95. https://doi.org/10.1016/J.XPHS.2018.11.039 .
Assegehegn G, Brito-de la Fuente E, Franco JM, Gallegos C. Freeze-drying: a relevant unit operation in the manufacture of foods, nutritional products, and pharmaceuticals. Adv Food Nutr. Res. 2020; 93:1–58. https://doi.org/10.1016/BS.AFNR.2020.04.001 .
Patel SM, Doen T, Pikal MJ. Determination of end point of primary drying in freeze-drying process control. AAPSPharmSciTech. 2010;11:73–84. https://doi.org/10.1208/S12249-009-9362-7 . (PMID: 10.1208/S12249-009-9362-7)
Patel SM, Pikal MJ. Emerging freeze-drying process development and scale-up issues. AAPS PharmSciTech. 2011;12:372–8. https://doi.org/10.1208/S12249-011-9599-9 . (PMID: 10.1208/S12249-011-9599-9213476203066344)
Solutions EV. The freeze drying theory and process-things to consider. Ellab White Pap. 2018:1–6.  https://www.ellab.com/wp-content/uploads/2020/08/the-freeze-drying-theory-and-process_ellab-whitepaper.pdf .
Bio-Resource: principle, methods & factors affecting lyophilization / freeze drying. (nd). http://technologyinscience.blogspot.com/2011/12/principle-methods-factors-affecting.html . Accessed 22 Jun 2023.
Introduction to freeze-drying and ice templating. 2018.  https://application.wiley-vch.de/books/sample/3527342729_c01.pdf .
Common mistakes when using a laboratory freeze dryer - Labconco. https://www.labconco.com/articles/common-mistakes-using-a-laboratory-freeze-dryer . Accessed 22 Jun 2023.
Bogdanova, Fureby AM, Kocherbitov V. Influence of cooling rate on ice crystallization and melting in sucrose-water system. J Pharm Sci. 2022;111:2030–7. https://doi.org/10.1016/J.XPHS.2022.01.027 .
The importance of critical temperatures in the freeze drying of pharmaceutical products. https://www.pharmaceuticalonline.com/doc/importance-criticaltemperatures-freeze-drying-0002 . Accessed 22 Jun 2023.
Depaz RA, Pansare S, Patel SM. Freeze-drying above the glass transition temperature in amorphous protein formulations while maintaining product quality and improving process efficiency. J Pharm Sci. 2016;105:40–9. https://doi.org/10.1002/JPS.24705 . (PMID: 10.1002/JPS.2470526580140)
Palmkron SB, Gustafson L, Wahlgren M, Bergensthål B, Fureby AM. Temperature and heat transfer control during freeze drying. effect of vial holders and influence of pressure. Pharm Res. 2022;39:2597–606. https://doi.org/10.1007/S11095-022-03353-4/FIGURES/9 .
Levenspiel O. The three mechanisms of heat transfer: conduction. convection and radiation. the three mechanisms of heat transfer: conduction, convection, and radiation. in: engineering flow and heat exchange. In: The Plenum Chemical Engineering Series. Springer, Boston. MA; 1984.
Jameel F, Alexeenko A, Bhambhani A, Sacha G, Zhu T, Tchessalov S, Kumar L, Sharma P, Moussa E, Iyer L, Fang R, Srinivasan J, Tharp T, Azzarella J, Kazarin P, Jalal M. Recommended best practices for lyophilization validation-2021 part I: process design and modeling. AAPS PharmSciTech. 2021;22(7):221. https://doi.org/10.1208/s12249-021-02086-8 . (PMID: 10.1208/s12249-021-02086-834409506)
Alba-Simionesco C, Judeinstein P, Longeville S, Osta O, Porcher F, Caupin F, Tarjus G. Interplay of vitrification and ice formation in a cryoprotectantaqueous solution at low temperature. PNAS. 2022;119(12):e2112248119. https://doi.org/10.1073/pnas.2112248119 .
Steven D Flemming. Cryoprotectants. https://fertility.coopersurgical.com/cryoprotectants/ .
Hauptmann A, Hoelzl G, Loerting T. Optical cryomicroscopy and differential scanning calorimetry of buffer solutions containing cryoprotectants. Eur J Pharm Biopharm. 2021;163:127–40. https://doi.org/10.1016/j.ejpb.2021.03.015 . (PMID: 10.1016/j.ejpb.2021.03.01533813056)
Luo C, Liu Z, Mi S, Li L. Quantitative investigation on the effects of ice crystal size on freeze-drying: the primary drying step. Drying Technol. 2022;40(2):446–58. https://doi.org/10.1080/07373937.2020.1806865 .
Liu X, Pan Y, Liu F, He Y, Zhu Q, Liu Z, Zhan X, Tan S. A review of the material characteristics, antifreeze mechanisms, and applications of cryoprotectants (CPAs). J Nanomater. 2021;(9990709):14.  https://doi.org/10.1155/2021/9990709 .
Jahed KR, Saini AK, Sherif SM. Coping with the cold: unveiling cryoprotectants, molecular signaling pathways, and strategies for cold stress resilience. Front Plant Sci. 2023;14. https://doi.org/10.3389/fpls.2023.1246093 .
Boafo GF, Magar KT, Ekpo MD, Qian W, Tan S, Chen C. The role of cryoprotective agents in liposome stabilization and preservation. Int J Mol Sci. 2022;23(20):12487. https://doi.org/10.3390/ijms232012487 . (PMID: 10.3390/ijms232012487362933409603853)
Jang TH, Park SC, Yang JH, Kim JY, Seok JH, Park US, Choi CW, Lee SR, Han J. Cryopreservation and its clinical applications. Integr Med Res. 2017;6(1):12–8. https://doi.org/10.1016/j.imr.2016.12.001 . (PMID: 10.1016/j.imr.2016.12.001284621395395684)
Lee MK, Kim MY, Kim S, Lee J. Cryoprotectants for freeze drying of drug nano-suspensions: effect of freezing rate. J Pharm Sci. 2009;98(12). https://doi.org/10.1002/jps .
Jang K, Kim HG, Hlaing SHS, Kang M, Choe H-W, Kim YJ. A short review on cryoprotectants for 3D protein structure analysis. Crystals. 2022;12:138. https://doi.org/10.3390/cryst12020138 . (PMID: 10.3390/cryst12020138)
Whaley D, Damyar K, Witek RP, Mendoza A, Alexander M, Lakey JR. Cryopreservation: an overview of principles and cell-specific considerations. Cell Transplant. 2021;30:963689721999617. https://doi.org/10.1177/0963689721999617 .
Pegg DE. Principles of cryopreservation. In: Day JG, Stacey GN, editors. Cryopreservation and freeze-drying protocols. Methods in molecular biology. US: Totowa (NJ: ): Humana Press; 2007. p. 39–75. (PMID: 10.1007/978-1-59745-362-2_3)
Szurek EA, Eroglu A. Comparison and avoidance of toxicity of penetrating cryoprotectants. PLoS ONE. 2011;6(11):e27604. https://doi.org/10.1371/journal.pone.0027604 .
Best, Ben. Cryoprotectant toxicity: facts, issues, and questions. Rejuvenation Res. 2015;18. https://doi.org/10.1089/rej.2014.1656 .
Date PV, Samad A, Devarajan PV. Freeze thaw: a simple approach for prediction of optimal cryoprotectant for freeze drying. AAPS Pharm Sci Tech. 2010;11(1). https://doi.org/10.1208/s12249-010-9382-3 .
Zhu S, Yu J, Liu S, Ding Y, Wang W, Zhou X. A bottom-up evaluation on cryoprotective potentials of gelatine from fish scale. Food Hydrocoll. 2022;124:107243. https://doi.org/10.1016/j.foodhyd.2021.107243 .
Cryopreservation of cells.  https://www.usp.org/sites/default/files/usp/document/our-work/biologics/resources/gc-1044-cryopreservation-of-cells.pdf .
Elbrink K, Van Hees S, Holm R, Kiekens F. Optimization of the different phases of the freeze-drying process of solid lipid nanoparticles using experimental designs. Int J Pharm. 2023;635:122717. https://doi.org/10.1016/j.ijpharm.2023.122717 .
Dalvi H, Bhat A, Iyer A, et al. Armamentarium of cryoprotectants in peptide vaccines: mechanistic insight, challenges, opportunities and future prospects. Int J Pept Res Ther. 2021;27:2965–82. https://doi.org/10.1007/s10989-021-10303-y . (PMID: 10.1007/s10989-021-10303-y346906218524217)
Dash SK, Patra CN, Acharjya SK, Jena GK, Panigrahi KC, Kumar NK, et al. Development and characterization of paliperidone loaded nanostructured lipid carrier. Indian J Pharm Edu Res. 2022;56:1003–12. https://doi.org/10.5530/ijper.56.4.181 . (PMID: 10.5530/ijper.56.4.181)
Bhattacharya S. Cryoprotectants and their usage in cryopreservation process.  https://doi.org/10.5772/intechopen.80477 .
Das A. Impact of continuous processing techniques on biologics supply chains. In: Continuous processing in pharmaceutical manufacturing. 2014. p. 53–70. https://doi.org/10.1002/9783527673681.ch03 . (PMID: 10.1002/9783527673681.ch03)
Plumb K. Continuous processing in the pharmaceutical industry: changing the mind set. Chem Eng Res Des. 2005;83(6):730–8. https://doi.org/10.1205/cherd.04359 . (PMID: 10.1205/cherd.04359)
Gerstweiler L, Bi J, Middelberg AP. Continuous downstream bioprocessing for intensified manufacture of biopharmaceuticals and antibodies. Chem Eng Sci. 2021;231:116272. https://doi.org/10.1016/j.ces.2020.116272 .
Kommineni N, Butreddy A, Jyothi VG, Angsantikul P. Freeze drying for the preservation of immunoengineering products. Iscience. 2022.
Hsein H, Auffray J, Noel T, Tchoreloff P. Recent advances and persistent challenges in the design of freeze-drying process for monoclonal antibodies. Pharm Dev Technol. 2022;27(9):942–55. https://doi.org/10.1080/10837450.2022.2131818 . (PMID: 10.1080/10837450.2022.213181836206457)
Aguilera JM, Flink JM. A combined experiment-computer technique for determining heating programs for batch and continuous freeze dryers. Int J Food Sci Technol. 1974;9(3):329–44. https://doi.org/10.1111/j.1365-2621.1974.tb01780.x . (PMID: 10.1111/j.1365-2621.1974.tb01780.x)
Gamiz AG, Van Bockstal PJ, De Meester S, De Beer T, Corver J, Dewulf J. Analysis of a pharmaceutical batch freeze dryer: resource consumption, hotspots, and factors for potential improvement. Dry Technol. 2019. https://doi.org/10.1080/07373937.2018.1518916 . (PMID: 10.1080/07373937.2018.1518916)
Oetjen GW. Industrial freeze-drying for pharmaceutical applications. Drugs Pharm Sci. 1999;96:267–335.
Kharaghani A, Tsotsas E, Wolf C, Beutler T, Guttzeit M, Oetjen GW. Freeze-drying Ullmann’s encycl ind chem. 2000;15:1–47.
Searles JA, Carpenter JF, Randolph TW. The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature-controlled shelf. J Pharm Sci. 2001;90(7):860–71. https://doi.org/10.1002/jps.1039 . (PMID: 10.1002/jps.103911458335)
Oddone I, Van Bockstal PJ, De Beer T, Pisano R. Impact of vacuum-induced surface freezing on inter-and intra-vial heterogeneity. Eur J Pharm Biopharm. 2016;103:167–78. https://doi.org/10.1016/j.ejpb.2016.04.002 . (PMID: 10.1016/j.ejpb.2016.04.00227063591)
Peters BH, Staels L, Rantanen J, Molnár F, De Beer T, Lehto VP, et al. Effects of cooling rate in microscale and pilot scale freeze-drying–variations in excipient polymorphs and protein secondary structure. Eur J Pharm Sci. 2016;95:72–81. https://doi.org/10.1016/j.ejps.2016.05.020 . (PMID: 10.1016/j.ejps.2016.05.02027221369)
Arsiccio A, Barresi A, De Beer T, Oddone I, Van Bockstal PJ, Pisano R. Vacuum induced surface freezing as an effective method for improved inter-and intra-vial product homogeneity. Eur J Pharm Biopharm. 2018;128:210–9. https://doi.org/10.1016/j.ejpb.2018.04.002 . (PMID: 10.1016/j.ejpb.2018.04.00229626510)
Kramer M, Sennhenn B, Lee G. Freeze-drying using vacuum-induced surface freezing. J Pharm Sci. 2002;91(2):433–43. https://doi.org/10.1002/jps.10035 . (PMID: 10.1002/jps.1003511835203)
Patel SM, Bhugra C, Pikal MJ. Reduced pressure ice fog technique for controlled ice nucleation during freeze-drying. AAPS PharmSciTech. 2009;10:1406–11. https://doi.org/10.1208/s12249-009-9338-7 . (PMID: 10.1208/s12249-009-9338-7199372842799604)
Bursac R, Sever R, Hunek B. A practical method for resolving the nucleation problem in lyophilization. Bio Process Int. 2009;7(9):66–72.
Pisano R, Arsiccio A, Nakagawa K, Barresi AA. Tuning, measurement and prediction of the impact of freezing on product morphology: a step toward improved design of freeze-drying cycles. Dry Technol. 2019;37(5):579–99. https://doi.org/10.1080/07373937.2018.1528451 . (PMID: 10.1080/07373937.2018.1528451)
Pikal MJ, Roy ML, Shah S. Mass and heat transfer in vial freeze-drying of pharmaceuticals: role of the vial. J Pharm Sci. 1984;73(9):1224–37. https://doi.org/10.1002/jps.2600730910 . (PMID: 10.1002/jps.26007309106491939)
Pikal MJ, Bogner R, Mudhivarthi V, Sharma P, Sane P. Freeze-drying process development and scale-up: scale-up of edge vial versus center vial heat transfer coefficients. Kv J Pharm Sci. 2016;105(11):3333–43. https://doi.org/10.1016/j.xphs.2016.07.027 . (PMID: 10.1016/j.xphs.2016.07.02727666376)
Rasetto V, Marchisio DL, Fissore D, Barresi AA. On the use of a dual-scale model to improve understanding of a pharmaceutical freeze-drying process. J Pharm Sci. 2010;99(10):4337–50. https://doi.org/10.1002/jps.22127 . (PMID: 10.1002/jps.2212720301092)
Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25:781–91. https://doi.org/10.1007/s11095-007-9511-1 . (PMID: 10.1007/s11095-007-9511-118185986)
Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding pharmaceutical quality by design. AAPS J. 2014;16:771–83. https://doi.org/10.1208/s12248-014-9598-3 . (PMID: 10.1208/s12248-014-9598-3248548934070262)
Fissore D, Pisano R, Barresi AA. Advanced approach to build the design space for the primary drying of a pharmaceutical freeze-drying process. J Pharm Sci. 2011;100(11):4922–33. https://doi.org/10.1002/jps.22668 . (PMID: 10.1002/jps.2266821702051)
Pisano R, Fissore D, Barresi AA, Rastelli M. Quality by design: scale-up of freeze-drying cycles in pharmaceutical industry. AAPS PharmSciTech. 2013;14:1137–49. https://doi.org/10.1208/s12249-013-0003-9 . (PMID: 10.1208/s12249-013-0003-9238848563755168)
Rambhatla S, Tchessalov S, Pikal MJ. Heat and mass transfer scale-up issues during freeze-drying, III: control and characterization of dryer differences via operational qualification tests. AAPS PharmSciTech. 2006;7:E61–70.
Fissore D, Pisano R, Barresi AA. Monitoring of the secondary drying in freeze-drying of pharmaceuticals. J Pharm Sci. 2011;100(2):732–42. https://doi.org/10.1002/jps.22311 . (PMID: 10.1002/jps.2231120799368)
De Beer TR, Vercruysse P, Burggraeve A, Quinten T, Ouyang J, Zhang X, Vervaet C, Remon JP, Baeyens WR. In-line and real-time process monitoring of a freeze drying process using Raman and NIR spectroscopy as complementary process analytical technology (PAT) tools. J Pharm Sci. 2009;98(9):3430–46. https://doi.org/10.1002/jps.21633 . (PMID: 10.1002/jps.2163319130604)
Oddone I, Fulginiti D, Barresi AA, Grassini S, Pisano R. Non-invasive temperature monitoring in freeze drying: control of freezing as a case study. Dry Technol. 2015;33(13):1621–30. https://doi.org/10.1080/07373937.2015.1040026 . (PMID: 10.1080/07373937.2015.1040026)
Nakagawa K, Hottot A, Vessot S, Andrieu J. Influence of controlled nucleation by ultrasounds on ice morphology of frozen formulations for pharmaceutical proteins freeze-drying. Chem. Eng. Process.: Process Intensif. 2006;45(9):783–91. https://doi.org/10.1016/j.cep.2006.03.007.
Harper JC, Tappel AL. Freeze-drying of food products. Adv Food Nutr Res. 1957;7:171–234. https://doi.org/10.1016/S0065-2628(08)60249-9 . (PMID: 10.1016/S0065-2628(08)60249-9)
Sluder JC, Olsen RW, Kenyon EM. A method for the production of dry powdered orange juice. Food Tech. 1947;1(1):85–94.
Oetjen GW, Haseley P. Freeze-drying. John Wiley & Sons; 2004.
Gea web page. 2017. https://www.gea.com/en/products/dryers-particle-processing/freeze-dryers/conrad-freeze-dryer.jsp . Accessed 26 Oct 2017.
Rey L. Glimpses into the realm of freeze-drying: classical issues and new ventures. In: Freeze drying/lyophilization of pharmaceutical and biological products. London: Informa Healthcare; 2010. p. 1–28.
Touzet A, Pfefferlé F, van der Wel P, Lamprecht A, Pellequer Y. Active freeze drying for production of nanocrystal-based powder: a pilot study. Int J Pharm. 2018;536(1):222–30. https://doi.org/10.1016/j.ijpharm.2017.11.050 . (PMID: 10.1016/j.ijpharm.2017.11.05029175644)
Saini R, Kaur S, Aggarwal P, Dhiman A, Suthar P. Conventional and emerging innovative processing technologies for quality processing of potato and potato-based products: a review. Food Control. 2023:109933.  https://doi.org/10.1016/j.foodcont.2023.109933 .
Pisano R, Arsiccio A, Capozzi LC, Trout BL. Achieving continuous manufacturing in lyophilization: technologies and approaches. Eur J Pharm Biopharm. 2019;142:265–79. https://doi.org/10.1016/j.ejpb.2019.06.027 . (PMID: 10.1016/j.ejpb.2019.06.02731252071)
Kullmann D, Martinez CL, Lümkemann J, Huwyler J. Part I: significant reduction of lyophilization process times by using novel matrix-based scaffolds Eur J Pharm Biopharm. 2023;184:248–61. https://doi.org/10.1016/j.ejpb.2022.12.008 .
Howard MD, Lu X, Jay M, Dziubla TD. Optimization of the lyophilization process for long-term stability of solid–lipid nanoparticles. Drug Dev Ind Pharm. 2012;38(10):1270–9. https://doi.org/10.3109/03639045.2011.645835 . (PMID: 10.3109/03639045.2011.64583522235767)
Zothanpuii F, Rajesh R, Selvakumar KJ. A review on stability testing guidelines of pharmaceutical products. Asian J Pharm Clin Res. 2020;13(10):3–9.
Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Deliv Rev. 2006;58(15):1688–713. https://doi.org/10.1016/j.addr.2006.09.017 .
Emami F, Keihan Shokooh M, Mostafavi Yazdi SJ. Recent progress in drying technologies for improving the stability and delivery efficiency of biopharmaceuticals. J Pharm Investig. 2023;53(1):35–57. https://doi.org/10.1007/s40005-022-00610-x . (PMID: 10.1007/s40005-022-00610-x36568503)
Trenkenschuh E, Friess W. Freeze-drying of nanoparticles, how to overcome colloidal instability by formulation and process optimization. Eur J Pharm Biopharm. 2021;165:345–60. https://doi.org/10.1016/j.ejpb.2021.05.024 .
Assefi M, Ataeinaeini M, Nazari A, Gholipour A, Vertiz-Osores JJ, Calla-Vásquez KM, Al-Naqeeb BZ, Jassim KH, Kalajahi HG, Yasamineh S, Dadashpour M, A state-of-the-art review on solid lipid nanoparticles as a nanovaccines delivery system. J Drug Deliv Sci Technol. 2023:104623. https://doi.org/10.1016/j.jddst.2023.104623 .
Ciurzynska A, Lenart A. Freeze-drying-application in food processing and biotechnology-a review. Pol J Food Nutri Sci. 2021;61.  https://doi.org/10.2478/v10222-011-0017-5 .
Barman RK, Iwao Y, Islam MR, Funakoshi Y, Noguchi S, Wahed MI, Itai S, In vivo pharmacokinetic and hemocompatible evaluation of lyophilization induced nifedipine solid-lipid nanoparticle. Pharmacol Pharma. 2014; 455–61. https://doi.org/10.4236/pp.2014.55055 .
Amekyeh H, Billa N. Lyophilized drug-loaded solid lipid nanoparticles formulated with beeswax and theobroma oi. Molecules. 2021;26:908. https://doi.org/10.3390/molecules26040908 . (PMID: 10.3390/molecules26040908335721687914714)
Wang JL, Hanafy MS, Xu H, Leal J, Zhai Y, Ghosh D, et al. Aerosolizable siRNA-encapsulated solid lipid nanoparticles prepared by thin-film freeze-drying for potential pulmonary delivery. Int J Pharm. 2021;596: 120215. https://doi.org/10.1016/j.ijpharm.2021.120215 . (PMID: 10.1016/j.ijpharm.2021.12021533486021)
Ai L, Li Y, Zhou L, Yao W, Zhang H, Hu Z et al. Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2. Cell Discov. 2023;9.  https://doi.org/10.1038/s41421-022-00517-9 .
Sanka K, Suda D, Bakshi V. Optimization of solid-self nanoemulsifying drug delivery system for solubility and release profile of clonazepam using simplex lattice design. J Drug Deliv Sci Technol. 2016;33:114–24. https://doi.org/10.1016/j.jddst.2016.04.003 . (PMID: 10.1016/j.jddst.2016.04.003)
Seo YG, Kim DW, Yousaf AM, Park JH, Chang PS, Baek HH, et al. Solid self-nanoemulsifying drug delivery system (SNEDDS) for enhanced oral bioavailability of poorly water-soluble tacrolimus: physicochemical characterization and pharmacokinetics. J Microencapsul. 2015;32:503–10. https://doi.org/10.3109/02652048.2015.1057252 . (PMID: 10.3109/02652048.2015.105725226079598)
Tashish AY, Shahba AA, Alanazi FK, Kazi M. Adsorbent precoating by lyophilization: a novel green solvent technique to enhance cinnarizine release from solid self-nanoemulsifying drug delivery systems (S-SNEDDS). Pharmaceutics. 2022;15:134. https://doi.org/10.3390/pharmaceutics15010134 . (PMID: 10.3390/pharmaceutics15010134366787669863206)
Kuncahyo I, Choiri S, Fudholi A. Solidification of meloxicam self-nano emulsifying drug delivery system formulation incorporated into soluble and insoluble carriers using freeze drying method. IOP Conf Ser Mater Sci Eng. 2019;578:012051.
Bose A, Roy Burman D, Sikdar B, Patra P. Nanomicelles: types, properties and applications in drug delivery. IET Nanobiotechnol. 2021;15:19–27. https://doi.org/10.1049/nbt2.12018 . (PMID: 10.1049/nbt2.12018346947278675821)
Wang G, Wang JJ, Chen XL, Du L, Li F. Quercetin-loaded freeze-dried nanomicelles: improving absorption and anti-glioma efficiency in vitro and in vivo. J Controlled Rel. 2016;235:276–90. https://doi.org/10.1016/j.jconrel.2016.05.045 . (PMID: 10.1016/j.jconrel.2016.05.045)
Yu Y, Chen D, Li Y, Yang W, Tu J, Shen Y. Improving the topical ocular pharmacokinetics of lyophilized cyclosporine A-loaded micelles: formulation, in vitro and in vivo studies. Drug Delivery. 2018;25:888–99. https://doi.org/10.1080/10717544.2018.1458923 . (PMID: 10.1080/10717544.2018.1458923296314686058700)
Gao W, Hu CM, Fang RH, Zhang L. Liposome-like nanostructures for drug delivery. J Mater Chem B. 2013;48:6569–85. (PMID: 10.1039/c3tb21238f)
Franze S, Selmin F, Samaritani E, Minghetti P, Cilurzo F. Lyophilization of liposomal formulations: still necessary, still challenging. Pharmaceutics. 2018;10:139. https://doi.org/10.3390/pharmaceutics10030139 . (PMID: 10.3390/pharmaceutics10030139301543156161153)
Yang S, Liu C, Liu W, Yu H, Zheng H, Zhou W, et al. Preparation and characterization of nanoliposomes entrapping medium-chain fatty acids and vitamin C by lyophilization. In J Mol Sci. 2013;14:19763–73. https://doi.org/10.3390/ijms141019763 . (PMID: 10.3390/ijms141019763)
Chen X, Long Q, Zhu L, Lu LX, Sun LN, Pan L, et al. A double-switch temperature-sensitive controlled release antioxidant film embedded with lyophilized nanoliposomes encapsulating rosemary essential oils for solid food. Mater. 2019;12:4011. https://doi.org/10.3390/ma12234011 . (PMID: 10.3390/ma12234011)
Shokri M, Tavallaie M, Hosseini SM. Effect of lyophilization on the size and polydispersity of unilamellar and multilamellar liposomes. J Nanotechnol Mater Sci. 2016;3:37–40. https://doi.org/10.15436/2377-1372.16.1139 .
Li C, Deng Y. A novel method for the preparation of liposomes: freeze drying of monophase solutions. J Pharm Sci. 2004;93:1403–14. https://doi.org/10.1002/jps.20055 . (PMID: 10.1002/jps.2005515124200)
Malik MA, Wani MY, Hashim MA. Microemulsion method: a novel route to synthesize organic and inorganic nanomaterials: 1st Nano Update. Arab J Chem. 2012;5:397–417. https://doi.org/10.1016/j.arabjc.2010.09.027 . (PMID: 10.1016/j.arabjc.2010.09.027)
Rochelle do Vale Morais Morais A, Xavier-Jr FH, do Nascimento Alencar E, Melo de Oliveira C, Dantas Santos N, Antonio Silva-JA, Optimization of the freeze-drying process for microemulsion systems. Drying Technol. 2019;37:1745–56.
Moreno MA, Frutos P, Ballesteros MP. Lyophilized lecithin-based oil-water microemulsions as a new and low toxic delivery system for amphotericin B. Pharm Res. 2001;18:344–51. https://doi.org/10.1023/a:1011011215418 . (PMID: 10.1023/a:101101121541811442275)
Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5:123–7. https://doi.org/10.1007/s13205-014-0214-0 .
do Vale Morais AR, do Nascimento Alencar É, Júnior FH, De Oliveira CM, Marcelino HR, Barratt G, Fessi H, Do Egito ES, Elaissari A. Freeze-drying of emulsified systems: a review. Int J Pharm. 2016;503:102–14. https://doi.org/10.1016/j.ijpharm.2016.02.047 .
Li F, Wang T, He HB, Tang X. The properties of bufadienolides-loaded nano-emulsion and submicro-emulsion during lyophilization. Int J Pharm. 2008; 349 : 291–9. https://doi.org/10.1016/j.ijpharm.2007.08.011 .
Kumar S, Gogoi AS, Shukla S, Trivedi M, Gulati S. Conclusion and future prospects of chitosan-based nanocomposites. In: Chitosan-based nanocomposite materials: fabrication, characterization and biomedical applications. Singapore: Springer Nature Singapore; 2022. p. 305–41. (PMID: 10.1007/978-981-19-5338-5_14)
Marciello M, Rossi S, Caramella C, Remuñán-López C. Freeze-dried cylinders carrying chitosan nanoparticles for vaginal peptide delivery. Carbohydr Polyms. 2017;170:43–51. https://doi.org/10.1016/j.carbpol.2017.04.051 .
Ataide JA, Geraldes DC, Gerios EF, Bissaco FM, Cefali LC, Oliveira-Nascimento L, et al. Freeze-dried chitosan nanoparticles to stabilize and deliver bromelain. J Drug Deliv Sci Technol. 2021;61:102225. https://doi.org/10.1016/j.jddst.2020.102225 .
Diop M, Auberval N, Viciglio A, Langlois A, Bietiger W, Mura C, et al. Design, characterization, and bioefficiency of insulin–chitosan nanoparticles after stabilization by freeze-drying or cross-linking. Int J Pharm. 2015;491:402–8. https://doi.org/10.1016/j.ijpharm.2015.05.065 . (PMID: 10.1016/j.ijpharm.2015.05.06526049075)
Mahdavi Z, Rezvani H, Moraveji MK. Core–shell nanoparticles used in drug delivery-microfluidics: a review. RSC Adv. 2020;10:18280–95. https://doi.org/10.1039/D0RA01032D . (PMID: 10.1039/D0RA01032D355171909053716)
Layre AM, Couvreur P, Richard J, Requier D, Eddine Ghermani N, Gref R. Freeze-drying of composite core-shell nanoparticles. Drug Devel Ind Pharm. 2006;32:839–46. https://doi.org/10.1080/03639040600685134 . (PMID: 10.1080/03639040600685134)
Dhadde GS, Mali HS, Raut ID, Nitalikar MM, Bhutkar MA. A review on microspheres: types, method of preparation, characterization and application. Asian J Pharm Technol. 2021;11:149–55. https://doi.org/10.52711/2231-5713.2021.00025 .
Pop OL, Diaconeasa Z, Brandau T, Ciuzan O, Pamfil D, Vodnar DC, et al. Effect of glycerol, as cryoprotectant in the encapsulation and freeze drying of microspheres containing probiotic cells, Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Food Sci Technol. 2015;72:27–32.  https://doi.org/10.15835/buasvmcn-fst:10993 .
Ma X, Santiago N, Chen YS, Chaudhary K, Milstein SJ, Baughman RA. Stability study of drug-loaded proteinoid microsphere formulations during freeze-drying. J Drug Target. 1994;2:9–21. https://doi.org/10.3109/10611869409015889 . (PMID: 10.3109/106118694090158898069587)
Song W, Xu J, Gao L, Zhang Q, Tong J, Ren L. Preparation of freeze-dried porous chitosan microspheres for the removal of hexavalent chromium. Appl Sci. 2021;11:4217. https://doi.org/10.3390/app11094217 .
Erdogar N, Akkın S, Bilensoy E. Nanocapsules for drug delivery: an updated review of the last decade. Recent Patent Drug Deliv Form. 2018;12:252–66. https://doi.org/10.2174/1872211313666190123153711 . (PMID: 10.2174/1872211313666190123153711)
Ohgaki K, Khanh NQ, Joden Y, Tsuji A, Nakagawa T. Physicochemical approach to nanobubble solutions. Chemical Eng Sci. 2010;65:1296–300. https://doi.org/10.1016/j.ces.2009.10.003 . (PMID: 10.1016/j.ces.2009.10.003)
Snell JR, Kumar NK, Suryanarayanan R, Randolph TW. Nanobubbles in reconstituted lyophilized formulations: interaction with proteins and mechanism of formation. J Pharm Sci. 2020;109:284–92. https://doi.org/10.1016/j.xphs.2019.05.005 . (PMID: 10.1016/j.xphs.2019.05.00531095959)
Kida H, Yamasaki Y, Feril LB Jr, Endo H, Itaka K, Tachibana K. Efficient mRNA delivery with lyophilized human serum albumin-based nanobubbles. Nanomater. 2023;13:1283. https://doi.org/10.3390/nano13071283 . (PMID: 10.3390/nano13071283)
Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Preat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Rel. 2012;161:505–22. https://doi.org/10.1016/j.jconrel.2012.01.043 . (PMID: 10.1016/j.jconrel.2012.01.043)
Abrego G, Alvarado HL, Egea MA, Gonzalez-Mira E, Calpena AC, Garcia ML. Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen. J Pharm Sci. 2014;103:3153–64. https://doi.org/10.1002/jps.24101 . (PMID: 10.1002/jps.2410125091511)
Parra A, Mallandrich M, Clares B, Egea MA, Espina M, García ML, et al. Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: ocular anti-inflammatory applications. Colloids Surf B. 2015;136:935–43. https://doi.org/10.1016/j.colsurfb.2015.10.026 .
Guterres SS, Alves MP, Pohlmann AR. Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug Target Insight. 2017;117739280700200002. https://doi.org/10.1177/117739280700200002 .
Curci A, Keller BL, Reul R, Moschwitzer J, Fricker G. Development and lyophilization of itraconazole loaded poly (butyl cyanoacrylate) nanospheres as a drug delivery system. Eur Pharm Sci. 2015;78:121–31. https://doi.org/10.1016/j.ejps.2015.07.010 . (PMID: 10.1016/j.ejps.2015.07.010)
Norizan MN, Moklis MH, Demon SZ, Halim NA, Samsuri A, Mohamad IS, et al. Carbon nanotubes: functionalisation and their application in chemical sensors. RSC Adv. 2020;10:43704–32. https://doi.org/10.1039/D0RA09438B . (PMID: 10.1039/D0RA09438B355196769058486)
Sweetman LJ, Moulton SE, Wallace GG. Characterisation of porous freeze dried conducting carbon nanotube–chitosan scaffolds. J Mater Chem. 2018;18:5417–22. (PMID: 10.1039/b809406n)
Hwa Y, Seo HK, Yuk JM, Cairns EJ. Freeze-dried sulfur–graphene oxide–carbon nanotube nanocomposite for high sulfur-loading lithium/sulfur cells. Nano lett. 2017;17:7086–94. https://doi.org/10.1021/acs.nanolett.7b03831 . (PMID: 10.1021/acs.nanolett.7b0383129035057)
Anoshkin IV, Campion J, Lioubtchenko DV, Oberhammer J. Freeze-dried carbon nanotube aerogels for high-frequency absorber applications. ACS Appl Mater Interf. 2018;10:19806–11. https://doi.org/10.1021/acsami.8b03983 . (PMID: 10.1021/acsami.8b03983)
He D, Mu S, Pan M. Improved carbon nanotube supported Pt nanocatalysts with lyophilization. Int J Hydrogen Energy. 2012;37:4699–703. https://doi.org/10.1016/j.ijhydene.2011.04.117 . (PMID: 10.1016/j.ijhydene.2011.04.117)
Arvizo R, Bhattacharya R, Mukherjee P. Gold nanoparticles: opportunities and challenges in nanomedicine. Expert Opin Drug Deliv. 2010;7:753–63. https://doi.org/10.1517/17425241003777010 . (PMID: 10.1517/17425241003777010204087362874072)
Hamaly MA, Abulateefeh SR, Al-Qaoud KM, Alkilany AM. Freeze-drying of monoclonal antibody-conjugated gold nanorods: colloidal stability and biological activity. Int J Pharm. 2018;550:269–77. https://doi.org/10.1016/j.ijpharm.2018.08.045 . (PMID: 10.1016/j.ijpharm.2018.08.04530145244)
Filipic B, Pantelic I, Nikolic I, Majhen D, Stoiic-Vukanic Z, Savic S, et al. Nanoparticle-based adjuvants and delivery systems for modern vaccines. Vaccines. 2023;11:1172. https://doi.org/10.3390/vaccines11071172 .
Trenkenschuh E, Friess W. Freeze-thaw stability of aluminum oxide nanoparticles. Int J Pharm. 2021;606:120932. https://doi.org/10.1016/j.ijpharm.2021.120932 .
Nayl AA, Abd-Elhamid AI, Aly AA, Brase S. Recent progress in the applications of silica-based nanoparticles. RSC Adv. 2022;12:13706–26. https://doi.org/10.1039/D2RA01587K . (PMID: 10.1039/D2RA01587K355303949073631)
Picco AS, Ferreira LF, Liberato MS, Mondo GB, Cardoso MB. Freeze-drying of silica nanoparticles: redispersibility toward nanomedicine applications. Nanomed. 2018;13:179–90. https://doi.org/10.2217/nnm-2017-0280 . (PMID: 10.2217/nnm-2017-0280)
Wang Y, Kho K, Cheow WS, Hadinoto K. A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid–polymer hybrid nanoparticles. Int J Pharm. 2012;424:98–106. https://doi.org/10.1016/j.ijpharm.2011.12.045 . (PMID: 10.1016/j.ijpharm.2011.12.04522226876)
Ngamcherdtrakul W, Sangvanich T, Reda M, Gu S, Bejan D, Yantasee W. Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery. Int J Nanomed 2018;4015–27.
Anhorn MG, Mahler HC, Langer K. Freeze drying of human serum albumin (HSA) nanoparticles with different excipients. Int J Pharm. 2008;363:162–9. https://doi.org/10.1016/j.ijpharm.2008.07.004 . (PMID: 10.1016/j.ijpharm.2008.07.00418672043)
Dadparvar M, Wagner S, Wien S, Worek F, von Briesen H, Kreuter J. Freeze-drying of HI-6-loaded recombinant human serum albumin nanoparticles for improved storage stability. Eur J Pharm Biopharm. 2014;88:510–7. https://doi.org/10.1016/j.ejpb.2014.06.008 . (PMID: 10.1016/j.ejpb.2014.06.00824995841)
Frank KJ, Boeck G. Development of a nanosuspension for iv administration: from miniscale screening to a freeze-dried formulation. Eur J Pharm Sci. 2016;87:112–7. https://doi.org/10.1016/j.ejps.2016.03.003 . (PMID: 10.1016/j.ejps.2016.03.00326970283)
Zhang T, Li X, Xu J, Shao J, Ding M, Shi S. Preparation, characterization, and evaluation of breviscapine nanosuspension and its freeze-dried powder. Pharmaceutics. 2022;14:923. https://doi.org/10.3390/pharmaceutics14050923 . (PMID: 10.3390/pharmaceutics14050923356315089143020)
Ansari MT, Hussain A, Nadeem S, Majeed H, Saeed-Ul-Hassan S, Tariq I, et al. Preparation and characterization of solid dispersions of artemether by freeze-dried method. BioMed Res Int. 2015. https://doi.org/10.1155/2015/109563 . (PMID: 10.1155/2015/109563260978424449868)
Mahjub R, Radmehr M, Dorkoosh FA, Ostad SN, Rafiee-Tehrani M. Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations. Drug Develop Ind Pharm. 2014;40:1645–59. https://doi.org/10.3109/03639045.2013.841187 . (PMID: 10.3109/03639045.2013.841187)
Gutierrez-Gonzalez CF, Agouram S, Torrecillas R, Moya JS, Lopez-Esteban S. Ceramic/metal nanocomposites by lyophilization: processing and HRTEM study. Mater Res Bullet. 2012;47:285–9. https://doi.org/10.1016/j.materresbull.2011.11.027 . (PMID: 10.1016/j.materresbull.2011.11.027)
Gol D, Thakkar S, Misra M. Nanocrystal-based drug delivery system of risperidone: lyophilization and characterization. Drug Delop Ind Pharm. 2018;44:1458–66. https://doi.org/10.1080/03639045.2018.1460377 . (PMID: 10.1080/03639045.2018.1460377)
Le HV, Dulong V, Picton L, Le Cerf D. Lyophilization for formulation optimization of drug-loaded thermoresponsive polyelectrolyte complex nanogels from functionalized hyaluronic acid. Pharmaceutics. 2023;15:929. https://doi.org/10.3390/pharmaceutics15030929 . (PMID: 10.3390/pharmaceutics150309293698678910053597)
Chua A, Tran TT, Pu S, Park JW, Hadinoto K. Lyophilization of curcumin–albumin nanoplex with sucrose as cryoprotectant: aqueous reconstitution, dissolution, kinetic solubility, and physicochemical stability. Int J Mol R Sci. 2022;23:11731. https://doi.org/10.3390/ijms231911731 . (PMID: 10.3390/ijms231911731)
Gomez L, Cebrian V, Martin-Saavedra F, Arruebo M, Vilaboa N, Santamaria J. Stability and biocompatibility of photothermal gold nanorods after lyophilization and sterilization. Mater Res Bull. 2013;48:4051–7. https://doi.org/10.1016/j.materresbull.2013.06.034 .
Salama AH, Aburahma MH. Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging. Pharm Develop Technol. 2016;21:706–15. https://doi.org/10.3109/10837450.2015.1048553 .
Mohammady M, Yousefi G. Freeze-drying of pharmaceutical and nutraceutical nanoparticles: the effects of formulation and technique parameters on nanoparticles characteristics. J Pharm Sci. 2020;109:3235–47. https://doi.org/10.1016/j.xphs.2020.07.015 . (PMID: 10.1016/j.xphs.2020.07.01532702373)
Fonte P, Reis S, Sarmento B. Facts and evidences on the lyophilization of polymeric nanoparticles for drug delivery. J Controlled Rel. 2016;225:75–86. https://doi.org/10.1016/j.jconrel.2016.01.034 . (PMID: 10.1016/j.jconrel.2016.01.034)
Nireesha GR, Divya L, Sowmya C, Venkateshan NN, Lavakumar V. Lyophilization/freeze drying-an review. Int J Novel Trend Pharm Sci. 2013;3:87–98.  https://scienztech.org/index.php/ijntps/article/view/96 .
European pharmaceutical review. https://www.europeanpharmaceuticalreview.com/article/70823/continuous-controlled-pharmaceutical-freeze-drying-technology-unit-doses/ . Accessed 4 Oct 2023.
Vauthier C, Bouchemal K. Methods for the preparation and manufacture of polymeric nanoparticles. Pharm Res. 2009;26:1025–58. https://doi.org/10.1007/s11095-008-9800-3 . (PMID: 10.1007/s11095-008-9800-319107579)
Jakubowska E, Lulek J. The application of freeze-drying as a production method of drug nanocrystals and solid dispersions–a review. J Drug Deliv Sci Technol. 2021;62:102357. https://doi.org/10.1016/j.jddst.2021.102357 .
Ledet GA, Graves RA, Bostanian LA, Mandal TK. Spray-drying of biopharmaceuticals, Lyophilized biologics and vaccines: modality-based approaches. 2015;273–97.
Dontireddy R, Crean AM. A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions. Drug Devel Ind Pharm. 2011;37:1141–9. https://doi.org/10.3109/03639045.2011.562213 . (PMID: 10.3109/03639045.2011.562213)
Tran P, Pyo YC, Kim DH, Lee SE, Kim JK, Park JS. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics. 2019;11:132. https://doi.org/10.3390/pharmaceutics11030132 . (PMID: 10.3390/pharmaceutics11030132308938996470797)
Gomez M, Archer M, Barona D, Wang H, Ordoubadi M, Karim SB. Microparticle encapsulation of a tuberculosis subunit vaccine candidate containing a nanoemulsion adjuvant via spray drying. Eur J Pharm Biopharm. 2021;163:23–37. https://doi.org/10.1016/j.ejpb.2021.03.007 . (PMID: 10.1016/j.ejpb.2021.03.007337532138096719)
Barbosa J, Borges S, Amorim M, Pereira MJ, Oliveira A, et al. Comparison of spray drying, freeze drying and convective hot air drying for the production of a probiotic orange powder. J Funct Foods. 2015;17:340–51. https://doi.org/10.1016/j.jff.2015.06.001 . (PMID: 10.1016/j.jff.2015.06.001)
Nail SL, Jiang S, Chongprasert S, Knopp SA. Fundamentals of freeze-drying, development and manufacture of protein. Pharm. 2002;281–360.  https://doi.org/10.1007/978-1-4615-0549-5_6 .
Challener C. For lyophilization, excipients really do matter. BioPharm Int. 2017;30(1):32–5.
Emami F, Vatanara A, Park EJ, Na DH. Drying technologies for the stability and bioavailability of biopharmaceuticals. Pharmaceutics. 2018;10:131. https://doi.org/10.3390/2Fpharmaceutics10030131 . (PMID: 10.3390/2Fpharmaceutics10030131301261356161129)
Esposito S. Traditional sol-gel chemistry as a powerful tool for the preparation of supported metal and metal oxide catalysts. Mater. 2019;12:668. https://doi.org/10.3390/ma12040668 .
Rajan M, Dharman G, Sumathra M. Development of microwave absorbers from biopolymer composites. In: Biopolymer composites in electronics. Elsevier; 2017. p. 231–53. https://doi.org/10.1016/B978-0-12-809261-3.00008-5 . (PMID: 10.1016/B978-0-12-809261-3.00008-5)
Assegehegn G, Brito-de la Fuente E, Franco JM, Gallegos C. Freeze-drying: a relevant unit operation in the manufacture of foods, nutritional products, and pharmaceuticals. In: Advances in food and nutrition research. Academic Press; 2020. p. 1–58. https://doi.org/10.1016/bs.afnr.2020.04.001 . (PMID: 10.1016/bs.afnr.2020.04.001)
Luo WC, Beringhs AO, Kim R, Zhang W, Patel SM, Bogner RH, et al. Impact of formulation on the quality and stability of freeze-dried nanoparticles. Eur J Pharm Biopharm. 2021;169:256–67. https://doi.org/10.1016/j.ejpb.2021.10.014 . (PMID: 10.1016/j.ejpb.2021.10.01434732383)
Wang Y, Grainger DW. Lyophilized liposome-based parenteral drug development: reviewing complex product design strategies and current regulatory environments. Adv Drug Deliv Rev. 2019;151:56–71. https://doi.org/10.1016/j.addr.2019.03.003 . (PMID: 10.1016/j.addr.2019.03.00330898571)
Samimi S, Maghsoudnia N, Eftekhari RB, Dorkoosh F. Lipid-based nanoparticles for drug delivery systems, characterization and biology of nanomaterials for drug delivery. 2019;47–76.  https://doi.org/10.1016/B978-0-12-814031-4.00003-9 .
Kumar N, Nautiyal U. A review article on lyophilization techniques used in pharmaceutical manufacturing. Int J Pharm Med Res J. 2017;5:478–84. www.ijpmr.org . Accessed 22 Jun 2023.
Lyophilization of parenteral. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-guides/lyophilization-parenteral-793 . Accessed 11 Nov 2014.
Bhambhani A, Jeffrey TB. Lyophilization strategies for development of a high-concentration monoclonal antibody formulation: benefits and pitfalls. Am Pharm Rev. 2010. https://www.americanpharmaceuticalreview.com/Featured-Articles/117600-Lyophilization-Strategies-for-Development-of-a-High-Concentration-Monoclonal-Antibody-Formulation-Benefits-and-Pitfalls/ .
Breen ED, Curley JG, Overcashier DE, Hsu CC, Shire SJ. Effect of moisture on the stability of a lyophilized humanized monoclonal antibody formulation. Pharm Res. 2001;18:1345–53. https://doi.org/10.1023/A:1013054431517 . (PMID: 10.1023/A:101305443151711683251)
Ciurzynska A, Lenart A. Freeze-drying-application in food processing and biotechnology-a review. Polish J Food Nutr Sci. 2011;61(3).
Freeze drying/lyophilization market - Global forecast to 2025. https://www.marketsandmarkets.com/Market-Reports/freeze-drying-lyophilization-equipment-market-24018886.html .

EEQ/2022/000008 Mission on Nano Science and Technology

Keywords: Cryoprotectant; Drug delivery; Freeze-drying; Lyophilization; Nanoparticles

Date Created: 20231120 Date Completed: 20240403 Latest Revision: 20240403

20240403

10.1007/s13346-023-01477-7

37985541