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Fun Sharing: The Relationship Between Ice Crystals and Frozen Foods (Part 1)

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    Development of Frozen Food

     

    It is hard to tell when various brands of frozen dumplings, glutinous rice balls, hand-grabbed pancakes, and frozen meats have filled up the freezer compartment of our refrigerators. Frozen foods are ubiquitous in supermarkets, hot pot restaurants, and online food delivery platforms. After work, compared to spending two hours shopping, washing, cooking, and cleaning dishes, I prefer a bowl of delicious dumplings that can be ready in just 15 minutes. Frozen foods have indeed freed up our hands and brought much convenience to our lives. In addition, due to the repeated outbreaks of the pandemic nowadays, it has become a trend to stock up on food and meat in the freezer for peace of mind. According to data provided by the National Bureau of Statistics, in 2019, the operating income of frozen food industrial enterprises above a certain scale in China reached 2.01 trillion yuan, a year-on-year increase of 9.5%, which was 5.7 and 5.3 percentage points higher than the increase rates of all industrial enterprises above a certain scale and the national food industry operating income respectively, achieving a high-speed growth. According to the prediction of China Market Research Puhua Institute, the frozen food industry in China will still be in the growth stage in the next ten years, with an expected compound annual growth rate of about 10%.

    crystalpharmatech-20221130-2-1.jpgcrystalpharmatech-20221130-2-2.jpgcrystalpharmatech-20221130-2-3.jpg 

    The preservation of frozen food itself is an effective, long-lasting, and cost-effective preservation method. But does this method have any impact on the quality of food? One day, as the author was in a hurry to cook dinner, he used hot water to thaw frozen pork and saw half a bag of blood water and some rotten meat fibers, which led to contemplation. The fried pork tasted bland. Upon further reflection, the beef repeatedly frozen in the refrigerator had long lost its original blood-red color. It is believed that everyone has had similar experiences, which are easily overlooked. Based on this, the author fully utilized his scientific talent and investigated the culprit behind all this - ice crystals. Now, let's hear its "defense"!

     

    Ice crystal: Hello everyone, I am Ice Crystal. I apologize for the impact I have had on the quality of your food. Please allow me to explain the following from several aspects.

     

    The Origin: The Mechanism and Process of Ice Crystals Formation from Water


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    It is common knowledge that the mother of ice crystals is ice, and ice comes from the freezing of water. But do you know the principle behind it? The key step in the formation of ice crystals is nucleation.


    According to the "classical nucleation theory", the crystallization of pure supercooled water is a homogeneous nucleation process, that is, it relies on its own atomic motion to form a nucleus. If a fine crystal of radius r is formed in supercooled water, the energy in this region will change, consisting of two parts: the volume free energy decreases due to the transformation of a certain volume of liquid into a solid; the surface of the fine crystal forms a liquid-solid phase interface, which increases the surface free energy. These two components have opposite impacts on the total free energy, which needs structure confirmation.


    ΔG = VΔGv + ΔG

            = 4πr3·ΔGv/3 + 4πr2σ


    ΔGv is the difference between the solid-liquid Gibbs free energy per unit volume, which is negative in supercooled water; σ is the interfacial energy, which is constant and positive. When fine crystals appear, their ability to grow depends on whether the free energy of the system decreases when their volume increases. When r is small, the surface free energy dominates, and as r increases, the system Gibbs free energy rises, and this spontaneous process decreases until it disappears and the crystal dissolves; when r is large, the bulk free energy dominates, and as r increases, the system Gibbs free energy decreases, and this fine crystal can grow and is called a nucleus.


    Thus there exists a critical nucleation radius r*, which makes a point of great value for ΔG, i.e., satisfying dΔG/dr = 0, yielding r* = -2σ/ΔGv.


    crystalpharmatech-20221130-2-6.jpg


    crystalpharmatech-20221130-2-7.jpg



    Text above: critical point, corresponding to the critical radius r*


    ΔG maxima, the stage where the start-up energy generated by subcooling overturns the energy barrier.


    The extreme value of ΔG is the free energy barrier for the homogeneous crystallization of supercooled water. The energy barrier is temperature dependent, and for pure supercooled water, the free energy barrier is easily crossed below -40 °C to form homogeneous crystallization. In practice, however, water freezing is a heterogeneous nucleation process, and nucleation occurs at the contact site between the liquid and solid boundaries. The solid-liquid interface can reduce the free energy required for nucleation, and the degree of supercooling is relatively low (a temperature difference that needs to be reached for crystallization to nucleate, and the temperature has to be lowered below the freezing point), thus making it easier to crystallize.


    Once nucleation has taken place, the ice crystals have to start growing. It is well known that all molecules are in constant motion, except that the molecular thermal motion of water molecules is diminished when ice is formed. However, the initial formation of the nucleus is not stable and easily dispersed by the thermal motion of other water molecules. Only when the temperature continues to drop to a certain level, the thermal motion of water molecules is further weakened to form a stable nucleus, which lays the foundation for the growth of ice crystals. The water molecules move and bind to the stable nuclei in an orderly manner, which also allows the ice crystals to grow larger and larger.


    crystalpharmatech-20221130-2-8.jpgText above: A: Sub-stable interval, supersaturation, sub-stable boundary, equilibrium solubility, concentration, temperature or solvent composition, oil formation, amorphous formation, spontaneous nucleation, secondary nucleation, crystal growth, crystallization.


    B: crystal species addition, concentration, solubility curve, supersaturation curve, crystal species addition, cooling crystallization, temperature, antisolvent addition to crystallization, amount of antisolvent addition.


    The nucleation and growth mentioned here is also the key to control the crystallization development process. The control of the crystallization process can be started from the point of view of regulating the nucleation or growth of crystals, but usually both factors need to be controlled simultaneously. From an overall results perspective, each unit parameter (e.g., temperature reduction rate, crystalline seed addition, antisolvent addition, etc.) needs to be evaluated to determine the most critical process parameters and thus which one of nucleation or growth plays a dominant role in the crystallization process.


    For the control of the crystallization process, the conventional view focuses mostly on nucleation, since the type, number and size of the initially formed nuclei are critical. However, there are multiple factors that can affect nucleation, nucleation rate and number of nuclei before growth dominates, often making the nucleation process difficult to control. Therefore, the focus of the crystallization process has to shift from nucleation control to growth control based on the control requirements of the physical properties of the final material, where the most critical control factors are supersaturation and crystal species.

    References
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Crystal Pharmatech Raring to Go to ChemOutsourcing 2022 ASD Column | Understanding the ASD Preparation Methods and Selecting the Optimal Method for Solution Crystal Bio Welcomes Dr. Shiaw-Lin (Billy) Wu as Co-Founder and Chief Scientific Officer CPHI North america - Meet Us at Booth #530 Polymorphs, Solvatomorphs and Hydrate of Dabrafenib Crystal Bio Appoints Dr. Ye Gu as Co-founder, CTO, and Head of USA BD Shining Glory: Unveiling the "True Eye" behind the Veil of Drug Crystal Forms Crystal Pharmatech's CDMO Business Unit - Crystal Formulations Services Successfully Passed EU QP Audit Crystal Pharmatech and Divamics Announce Strategic Collaboration to Accelerate Drug Development through AI, Crystal Form, and Formulation Innovation Applications of Dynamic Moisture Adsorption in Crystal Research Meet Crystal Pharmatech at AAPS National Biotechnology Conference Application of Granularity Analysis in Crystal Typing Research Assessment of CQA in mRNA-LNP Modality DCAT Week 2025 A Brief Introduction to Amorphous Solid Dispersion Technology ADME Simulations: Insights into Bioavailability and Pharmacokinetics 19th WRIB (Workshops on Recent Issues in Bioanalysis)  Understand ASD Manufacturing Strategies, Choose the Optimal One Parameter Sensitivity with GastroPlus Review of Polymorph Patent Application of 30 Small Molecule New Drugs Approved by the FDA in 2023 Unveil Key Factors Influencing the Physical Stability of Amorphous Solid Dispersions Characterization and Evaluation of Amorphous Solid Dispersion (ASD) - Part 1 Optimizing Polymer Selection for Amorphous Solid Dispersion in Hot Melt Extrusion Processes Crystal’s Perspective: Polymorph Patent Landscape of 28 FDA-Approved Small Molecule Drugs in 2024 How to Mitigate Disproportionation of API Salts in Pharmaceutical Formulations
    Solid Form Screening Solid Form Developability Evaluation Absolute Structure Determination Crystallization Process Development The Purpose Behind Molecules to Medicine Repurposing Dexmedetomidine into an Oral Sleep-Enhancing Medication The Role of Collaboration in Optimizing the Development of HIF Inhibitors for the Treatment of Advan Mol2Med™ Integrated Services AAPS 2024 PHarmSCi 360 Concerned about mRNA -LNP Integrity during International Shipping? Improving the Manufacture of mRNA Biologics Patient-Centered Controlled and Modified Release Drug Delivery: Formulation & Process Development BIO International Convention Home Formulation Development Solid Form Screening and Selection Our Company Talent Recruitment Case Study 1: Indinavir - Early Salt Form Change The Tiny-TIM System Whitepaper Solid Form Research Engineering Cocrystal Solubility and Streamlining Cocrystal Early Development The Use of Amorphous Solid Dispersions to Enhance Dissolution, and Oral Bioavailability of Poorly Water-Soluble Pharmaceutical C Biologics CMC Analytical Services High-Resolution Mass Spectrometry Crystal Pharmatech Formulation Forum News & Events Optimizing Polymer Selection for Amorphous Solid Dispersion in Hot Melt Extrusion Processes Formulation & Delivery US 2024 Concerned about mRNA -LNP Integrity during International Shipping? Analytical Techniques to Assess the mRNA 5' Cap How to Mitigate Disproportionation of API Salts in Pharmaceutical Formulations Small Molecule Solid-State Characterization/FAST Conventional Oral Solid Dosage Forms Our History News Our Business Case Study 2: DPC 961 – Form Change On A Fast Track Compound Detecting and Avoiding Disappearing Polymorph Cases by Crystal Structure Prediction Preclinical and Tox Formulation Development Synthonic Engineering: Tools for the Rational Design of High Quality Pharmaceuticals Polymorphism of Drugs - Can We Exploit Physical Form in the Development of Low Solubility Molecules? Bioanalysis and Biomarker Services 2023-Mol2Med™ First-Time-Right Approach Webinar Series Date: 2:00-3:00 pm EDT, Wednesday, Watch on-demand
    Developability Assessment Oral Solid Dosage Forms ASD Series Development and Production Application Cases of Amorphous Solid Dispersion Formulations (II) - Spray Drying CATUG and Crystal Bio Establish Strategic Partnership, Launching “CATUG-Crystal” Joint Lab Dedicated to Advanced Nucleic Acid Analytical Services Characterization and Evaluation of Amorphous Solid Dispersion - Part 2 Critical Quality Attribute (CQA) in Antibody Drug Conjugate (ADC) Modality Unlocking the Power of AI in Pharmaceutical Development The 16th Drug Discovery Strategic Summit (DDSS) - San Francisco Bioanalytical and Biomarker Services Crystal’s Perspective: Polymorph Patent Landscape of 28 FDA-Approved Small Molecule Drugs in 2024 Single Crystal Growth & Structure Determination Bioavailability Enhancement for Insoluble Compounds & PROTAC & Oral Peptides Our People Events Case Study 3: Atorvastatin - Crystalline Form Change In Late Development Selecting the Right API Form and Formulation Instrumentation for Electron Diffraction, Applications, and Case Studies Effective Development of API Crystallization Processes During Drug Development Efficient Preclinical Formulation Development for Poorly Soluble Compounds pKa/LogP/LogD Measurements Date: 2:00-3:00 pm EDT, Wednesday, Watch on-demand
    Amorphous Solid Dispersion (Spray Drying & Hot-melt Extrusion) Dr. LianFeng Huang Joins Crystal Pharmatech as Chief Scientist Biologics Characterization and Evaluation of Amorphous Solid Dispersion (ASD) - Part 1 Characterization and Evaluation of Amorphous Solid Dispersion-Part 2 ADME Simulations: Insights into Bioavailability and Pharmacokinetics Utilizing Compaction Simulation for Advancing Oral Dosage Formulation Design Critical Quality Attribute D0 Impact in ADC Modality SAPA Annual Conference (Gold Corporate Sponsorship) Crystal Bio Solutions Bio Analytics API Form and Solid-State Research Crystallization Development Mini-tablet Knowledge Hub Molecules-to-Medicine: Accelerating Drug Development through Collaboration PBPK in Preclinical/FIH Scenarios Case Study 4: Gatifloxacin - Crystalline Form Changes With A Licensed Compound Presentations Using Thermodynamic Phase Maps in API Crystallization Process Design Pre-clinical Formulation Strategies Sponsored by Crystal Pharmatech Date: 2:00-3:00 pm EDT, Wednesday, Whatch on-demand
    Stability and Solubility Studies Comprehensive Physicochemical Property Evaluation Pediatric Formulation (Mini-tablet) Crystal Formulation Services successfully passed the dual certification of GMP and GDP conducted by SGS Development and Production Application Cases of Amorphous Solid Dispersion Formulations (I) - Hot Melt Extrusion Unveil Key Factors Influencing the Physical Stability of Amorphous Solid Dispersions Assessment of CQA in mRNA-LNP Modality Parameter Sensitivity with GastroPlus 14th American Drug Delivery and Formulation Summit (Exhibit) Developability Assessment, Pre-formulation Study for IND Enabling Product Quality Analysis Additional Capabilities Chiral Separation Technology Our Partner Advanced Characterization: Tools for Accelerating Molecules to Medicine Tools for Accessing New Solid Forms Case Studies Case Study 5: Lifecycle Management - Olanzapine - Crystalline Change From Free Acid to Salt Amorphous Solid Dispersions Enabling Poorly Soluble Weak Bases for Improved Bioavailability: Why a Salt May Not be the Best Choice Integrated Phase and Formulation Selection to Support GLP Toxicology and First in Human Studies Sponsored by Crystal Pharmatech In-Silico PBPK Modeling and Simulation Industry Shift: FDA Goes Vegan? Date: 2:00-3:00 pm EDT, Wednesday,Watch on-demand
    Crystallization Development Services Excipient Selection and Compatibility Studies Analytical Chemistry Unlock Solubility Enhancement Methods for Poorly Soluble Oral Drugs Development and Production Application Cases of Amorphous Solid Dispersion Formulations (II) - Spray Drying Sterility Assays in Drug/Device Manufacturing Overcoming Bioavailability Barrier to Deliver Protein Degraders 2024 CASSS - Mass Spec Symposium Flow Cytometry About Us Pre-formulation Studies Formulations for PK/Efficacy/Tox Studies Crystallization and Spray Drying Process Development, Scale-Up, and Technology Transfer Case Study 6: Oxybutynin- Crystalline Change From Salt to Free Base Technical Articles Learn about Drug Eutectic Screening Crystal Pharmatech's CDMO Business Unit - Crystal Formulation Services Received China Drug Product Manufacturing License, Achieving the Important Milestone in Formulation Capability Development and Production Application Cases of Amorphous Solid Dispersion Formulations (I) - Hot Melt Extrusion Overcoming Poor Solubility and Dissolution of Insoluble Molecules Patent Analysis of Resmetirom ChemOutsourcing 2024 Crystal Bio Webinar ELISpot Assays Solid-State NMR Analysis Resources Avoiding Drug Failures: Right First Time; Fast First Time Exploring the Pharmaceutical Solid State by Molecular Simulation Crystallization Process Method SMART Development of Pre-clinical Candidates Crystal Pharmatech Recognized as "Best Partner" by Allorion Therapeutics for Excellent Services Formulation and Analytical Development Animal Dosing Vehicle Selection Understand ASD Manufacturing Strategies, Choose the Optimal One Review of Polymorph Patent Application of 30 Small Molecule New Drugs Approved by the FDA in 2023 Immuno-Oncology Summit 2024 - Meet Crystal Bio at Booth 15 Molecular Biology Clinical and Commercial Manufacturing Amorphous Solid Dispersions Careers Tools and Strategies for De-risking Rapid Drug Substance and Drug Product Development Crystal Pharmatech Returned to AAPS 2022 PharmSci 360 Fun Sharing: The Secret Behind the Silky Smoothness of Chocolate (Part 2) GMP Manufacturing Detecting Low-Level Crystallinity in ASD-like Samples Using ssNMR Techniques A Brief Introdction to Amorphous Solid Dispersion Technology FIH-PMF-FMF Manufacturing The Bioprocessing Summit 2024 - Meet Crystal Bio at Booth T13 Contact Us Crystal Pharmatech and Particle Sciences Form a US-China Pharmaceutical CRO Partnership Advancements in Analytical Tools for API and DP Characterization API Crystallization Fun Sharing: The Secret behind the Silky Smooth Enjoyment of Chocolate (Part 3) Unlock Solubility Enhancement Methods for Poorly Soluble Oral Drugs Amorphous Solid Dispersions: Two Heads Are Better Than One Meet Crystal Pharmatech at 2024 Controlled & Modified Drug Release Summit Search Result Webinar Series Crystal Pharmatech Raises $10 Million to Accelerate Growth Solid Forms: The Good; The Bad; The Ugly Co-crystals Fun Sharing: The Secret Behind the Silkiness of Chocolate (Part 1) Join Crystal Pharmatech for the Sino-American Pharmaceutical Professionals Association (SAPA) NE 26th Annual Conference Assessment of Powder Segregation in Direct Compression (DC) Blends: Developing Predictive and PAT Tools Sitemap Crystal Formulation Services, Formulation Tailor-made for Your Molecules Utility of Single Crystal in Form and Formulation Selection Impact of Solid-state in Early Development ​Crystal Pharmatech will be in San Diego from June 3-6 at BIO International Convention Formulation Design and Development of Fixed Dose Combination Solid Oral Dosage Forms 404 Candoo Enables the Successful Development of a BCS 4 Combo Drug Product Introduction to MicroED Technology and Solutions Optimal Preclinical Formulation Development Fun Sharing:The Story Between Ice Crystals and Frozen Foods (Part 3) Meet Crystal Pharmatech at Chinese Antibody Society 2024 Annual Conference Drug Delivery and Patient Centric Approaches to Drug Development  Privacy Policy International Company Crystal Pharmatech Finds CCIT An Optimal Spot for First US Location Formulation Implications Salts Meet Crystal Pharmatech at 15th Drug Discovery Strategic Summit (DDSS) Submission Successful! Crystal Pharmatech Triples Headquarters in Biobay, China, with More Floors and Labs Pharmaceutical Solid-state Forms Fun Sharing: The Relationship Between Ice Crystals and Frozen Foods (Part 1) Clinical Supply Meet Crystal Pharmatech at Sorption Symposium North America 2024 Taggg Xceleron and Crystal Pharmatech Announce Partnership to Improve Early Clinical Development Utilizing Absolute Bioavailability Trials and Solid-State Solutions CPHI North America - Meet Crystal Pharmatech at Booth 1441 Search Result Service Crystal Pharmatech Introduces Customized Service Packages for Customers Seeking Materials Science Approaches in Drug Discovery and Development Fun Sharing: The Story of Ice Crystals and Frozen Foods (Part 2) Meet Crystal Pharmatech at MIDD+ Boston 2024 Meina Liang, Ph.D. Search Result Others Crystal Pharmatech Expands Leadership Team Case Study on Development and Production Applications of Amorphous Solid Dispersions - Hot Melt Extrusion Formulation Development: Fastest-to-FIH Without Sacrificing Quality Crystal Formulation Services(CFS)Opens New Formulation Development Center and Analytical R&D Lab in Suzhou, China event page Development and Production Application Case Study of Amorphous Solid Dispersions: Spray Drying DCAT WEEK: CMC Discussions Amorphous Solid Dispersion Technology and the Service Advantages of Crystal Pharmaceutical AAPS PharmSci360 - Meet Us at Booth # 2106 Candoo's Formulation Technology Platform Featured in the Drug Development & Delivery Journal ASD Column | Mastering Stable Art: Unveiling Key Factors Influencing Physical Stability of Amorphous Solid Dispersions Meet the Crystal Pharmatech formulation team next week at CPHI Crystal Pharmatech and the Future of Pharma at AAPS PharmSci 360 Crystal Formulation Services' GMP Manufacturing Facility Successfully Passes the Remote Audit by US Client, Marking a Key Milestone for Its International Expansion ASD Column | How to Select Polymers in Hot-melt Extrusion Process? Crystal Pharmatech Raring to Go to ChemOutsourcing 2022 ASD Column | Understanding the ASD Preparation Methods and Selecting the Optimal Method for Solution Crystal Bio Welcomes Dr. Shiaw-Lin (Billy) Wu as Co-Founder and Chief Scientific Officer CPHI North america - Meet Us at Booth #530 Polymorphs, Solvatomorphs and Hydrate of Dabrafenib Crystal Bio Appoints Dr. Ye Gu as Co-founder, CTO, and Head of USA BD Shining Glory: Unveiling the "True Eye" behind the Veil of Drug Crystal Forms Crystal Pharmatech's CDMO Business Unit - Crystal Formulations Services Successfully Passed EU QP Audit Crystal Pharmatech and Divamics Announce Strategic Collaboration to Accelerate Drug Development through AI, Crystal Form, and Formulation Innovation Applications of Dynamic Moisture Adsorption in Crystal Research Meet Crystal Pharmatech at AAPS National Biotechnology Conference Application of Granularity Analysis in Crystal Typing Research Assessment of CQA in mRNA-LNP Modality DCAT Week 2025 A Brief Introduction to Amorphous Solid Dispersion Technology ADME Simulations: Insights into Bioavailability and Pharmacokinetics 19th WRIB (Workshops on Recent Issues in Bioanalysis)  Understand ASD Manufacturing Strategies, Choose the Optimal One Parameter Sensitivity with GastroPlus Review of Polymorph Patent Application of 30 Small Molecule New Drugs Approved by the FDA in 2023 Unveil Key Factors Influencing the Physical Stability of Amorphous Solid Dispersions Characterization and Evaluation of Amorphous Solid Dispersion (ASD) - Part 1 Optimizing Polymer Selection for Amorphous Solid Dispersion in Hot Melt Extrusion Processes Crystal’s Perspective: Polymorph Patent Landscape of 28 FDA-Approved Small Molecule Drugs in 2024 How to Mitigate Disproportionation of API Salts in Pharmaceutical Formulations
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