Lyophilization, also known as freeze drying, is a process used to remove water from materials while preserving their structure. It involves freezing the material and then reducing pressure to allow the frozen water to sublimate from the solid to gas phase. The process is carried out below the triple point of water to enable sublimation of ice. Freeze drying has applications in the food and pharmaceutical industries as it can preserve thermolabile compounds and materials by removing water while retaining quality.
Dehydration process,
Typically used to preserve a perishable material or make the material more convenient for transport,
Mostly used for light food required by astronauts, hikers
Dehydration process,
Typically used to preserve a perishable material or make the material more convenient for transport,
Mostly used for light food required by astronauts, hikers
Use Of Freeze Drying Microscopy To Determine Critical ParametersBTL
Materials for freeze drying should be characterised in order to ensure that freeze-drying takes place below their intrinsic critical temperature (Tc / Teu). This presentation evaluates freeze drying microscopy, an established technique for formulation analysis.
Use Of Freeze Drying Microscopy To Determine Critical ParametersBTL
Materials for freeze drying should be characterised in order to ensure that freeze-drying takes place below their intrinsic critical temperature (Tc / Teu). This presentation evaluates freeze drying microscopy, an established technique for formulation analysis.
Definition of drying
Importance of drying
Difference between drying and evaporation
Equipments
References
Definition
A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation (primary drying stage) and then desorption (secondary drying stage) to values that will no longer support biological activity or chemical reactions.
History
Freeze drying was first actively developed during WORLD WAR II transport of serum.
The main aim was to store the products without refrigeration and to remove moisture from thermolabile compounds.
Atlas in 1961 built 6 production freeze drying cabinet for Nestle group in Germany, Holland.
Principle
Lyophilization is carried out using a simple principle of physics sublimation. Sublimation is the transition of a substance from the solid to the vapour state, without first passing through an intermediate liquid phase.
Lyophilization is performed at temperature and pressure conditions below the triple point, to enable sublimation of ice.
The entire process is performed at low temperature and pressure by applying vacuum, hence is suited for drying of thermolabile compounds.
The concentration gradient of water vapour between the drying front and condenser is the driving force for removal of water during lyophilization.
Lyophilization or freeze drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. The process consists of three separate, unique, and interdependent processes; freezing, primary drying (sublimation), and secondary drying (desorption).
The advantages of lyophilization include:
Ease of processing a liquid, which simplifies aseptic handling
Enhanced stability of a dry powder
Removal of water without excessive heating of the product
Enhanced product stability in a dry state
Rapid and easy dissolution of reconstituted product
Disadvantages of lyophilization include:
Increased handling and processing time
Need for sterile diluent upon reconstitution
Cost and complexity of equipment
The lyophilization process generally includes the following steps:
Dissolving the drug and excipients in a suitable solvent, generally water for injection (WFI).
Sterilizing the bulk solution by passing it through a 0.22 micron bacteria-retentive filter.
Filling into individual sterile containers and partially stoppering the containers under aseptic conditions.
Transporting the partially stoppered containers to the lyophilizer and loading into the chamber under aseptic conditions.
Freezing the solution by placing the partially stoppered containers on cooled shelves in a freeze-drying chamber or pre-freezing in another chamber.
Applying a vacuum to the chamber and heating the shelves in order to evaporate the water from the frozen state.
Complete stoppering of the vials usually by hydraulic or screw rod stoppering mechanisms installed in the lyophilizers.
There are many new parenteral products, including anti-infectives, biotechnology derived products, and in-vitro diagnostics which are manufactured as lyophilized products. Additionally, inspections have disclosed potency, sterility and stability problems associated with the manufacture and control of lyophilized products. In order to provide guidance and information to investigators, some industry procedures and deficiencies associated with lyophilized products are identified in this Inspection Guide.
It is recognized that there is complex technology associated with the manufacture and control of a lyophilized pharmaceutical dosage form. Some of the important aspects of these operations include: the formulation of solutions; filling of vials and validation of the filling operation; sterilization and engineering aspects of the lyophilizer; scale-up and validation of the lyophilization cycle; and testing of the end product. This discussion will address some of the problems associated with the manufacture and control of a lyophilized dosage form.
The process of freeze drying with greater emphasis on the uses in the fisheries food processing sector. The presentation shows the process involved and the different steps involved and the effect of the process on the food material.
Definition and Objectives of Lyophilization, Advantages & Disadvantages, Basic Principles of Lyophilization, Steps of Lyophilization,
Main Components of Lyophilizer,
Qualification of Lyophilizer,
Development of Lyophilization cycle, Defects of Lyophilizer.
Freezing has been successfully employed for the long-term preservation of many foods, providing a significantly extended shelf life.
The process involves lowering the product temperature generally to -18 °C or below.The extreme cold simply retards the growth of microorganisms and slows
down the chemical changes that affect quality or cause food to spoil.
During freezing the cellular solution present in the food matrix is cooled to its initial freezing point, and further cooling causes the water molecule to
separate, forming ice crystal.
The migration of water molecules during crystallization led to an increase in osmotic pressure, further enhancing the water permeability of the cell membranes. This transport of water molecules, if not controlled, can eventually affect the microstructure of the frozen produce.
The freezing process occurs in two successive steps, i.e,
” NUCLEATION” and “CRYSTAL GROWTH”.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
3. CONTENTS
Definition
Principle
Components of freeze dryer
Steps involved in lyophilization
Advantages of freeze drying over conventional drying
Advantages
Disadvantages
Applications
Conclusion
References
4. DEFINITION
A stabilizing process in which a substance is first frozen
and then the quantity of the solvent is reduced, first by
sublimation (primary drying stage) and then desorption
(secondary drying stage) to values that will no longer
support biological activity or chemical reactions.
5. PRINCIPLE
Lyophilization is carried out using a simple principle of physics
sublimation. Sublimation is the transition of a substance from the
solid to the vapour state, without first passing through an
intermediate liquid phase.
Lyophilization is performed at temperature and pressure
conditions below the triple point, to enable sublimation of ice.
The entire process is performed at low temperature and pressure
by applying vacuum, hence is suited for drying of thermolabile
compounds.
The concentration gradient of water vapour between the drying
front and condenser is the driving force for removal of water
during lyophilization.
6. is carried out below the triple point to enableLyophilization
sublimation of ice.
Fig 1. Phase diagram showing the triple point of water at 0.01°C,
0.00603 atm.
8. FREEZE DRYER DESIGN
ESSENTIAL COMPONENTS
CHAMBER
– This is the vacuum tight box, sometimes called the lyophilization
chamber or cabinet.
– The chamber contains shelf or shelves for processing product.
– The chamber can also fit with a stoppering system.
– It is typically made of stainless steel and usually highly polished
on the inside and insulated and clad on the outside.
– The door locking arrangement by a hydraulic or electric motor.
SHELVES
– The shelf act as a heat exchanger, supplying energy to the
product during the primary and secondary drying segments of
the freeze drying cycle
– The shelves will be connected to the silicone oil system through
either fixed or flexible hoses.
9. REFRIGERATION SYSTEM
– The product to be freeze dried is frozen whilst on the
shelves.
– Compressors or sometimes-liquid nitrogen supplies the
cooling energy.
– Most often multiply compressors are needed and the
compressor may perform two duties, one to cool the
shelves and the second to cool the process condenser.
10. SHELF FLUID SYSTEM
– The freeze-drying process requires that the product is first
frozen and then energy in the form of heat is applied
throughout the drying phases of the cycle.
– This energy exchange is traditionally done by circulating a
silicone oil through the shelves at a desired temperature.
– The temperature is set in an external heat exchange system
consisting of cooling heat exchangers and an electrical
heater.
11. PROCESS CONDENSER
– The process condenser is sometimes referred as just the condenser or the
cold trap.
– It is designed to trap the solvent, which is usually water, duringthe
drying process.
– The process condenser will consist of coils or sometimes plates which
are refrigerated to allow temperature.
– These refrigerated coils or plates may be in a vessel separate to the
chamber, or they could be located within the same chamber as the
shelves.
– Hence there is designation “external condenser” and “internal
condenser”. Physically, the external condenser is traditionally placed
behind the chamber.
– For an internal condenser the refrigerated coils or plates areplaced
beneath the shelves. The position of the condenser does not affect
trapping performance.
13. 1. PRETREATMENT
• Pretreatment includes any method of treating the product prior to freezing.
• This may include
1. Concentrating the product,
2. Formulation revision (i.e., addition of components to increasestability
and/or improve processing),
3. Decreasing a high vapor pressure solvent or
4. Increasing the surface area.
14. 2. FREEZING
• The product must is frozen to a low enough temperature to be completely
solidify.
• The method of prefreezing and the final temperature of the frozen product
can affect the ability to successfully freeze dry the material.
• Rapid cooling results in small ice crystals, useful in preserving structures to
be examined microscopically, but resulting in a product that is, more
difficult to freeze dry.
• Slower cooling results in large ice crystals.
15. • Most samples that are to be freeze dried are eutectics, which
are mixtures of substances that freeze at lower temperature
than the surrounding water.
• It is very important in freeze-drying to pre freeze the product
to below the eutectic temperature before beginning the freeze-
drying process.
• The second type of frozen product is a suspension that
undergoes glass formation during the freezing process.
16. 3. PRIMARY DRYING
• After prefreezing the product, conditions must be established in which ice
can be removed from the frozen product via sublimation, resulting in a dry,
structurally intact product.
• This requires very carefully control of the two parameters.
1. Temperature (-10 °C to 30°C) and
2. Pressure involved in freeze-drying system(50mmHg).
• The rate of sublimation of ice from a frozen product depends upon the
difference in vapor pressure of the product compared to the vapor pressure
of the ice collector.
17. • Heat enters the products by one of several mechanisms: -
1. By direct contact between the container base and the
shelf, so here the shape of the container is important.
2. By conduction across the container base and then through
the frozen mass to the drying front (also called the
sublimation interface)
3. By gaseous convection between the product and residual
gas molecules in the chamber.
4. By radiation
• Convection is certainly the most important of these
mechanisms
18. DETERMINATION OF THE END OF PRIMARY
DRYING
• Several analytical methods are available for
determining that primary drying is
complete. The most basic method is to
monitor the product temperature with a
thermocouple probe. The measured product
temperature will be colder than the shelf
temperature set point during active primary
drying because the heat from the shelf is
being used for the sublimation phase
change. When sublimation of ice crystals is
complete, the product temperature will
increase and approach the shelf
temperature. When the product temperature
equals the shelf temperature, it can be
inferred that primary drying is complete.
19. 4. SECONDARY DRYING
• After primary freeze-drying about 7-8% residual moisture content is
present so continues drying at warmer temperature is necessary to reduce
the residual moisture content to optimum values.
• This process is called ‘Isothermal Desorption’ as the bound water is
desorbed from the product.
• Secondary drying is normally continued at a product temperature higher
than ambient but compatible with the sensitivity of the product.
• In contrast to processing conditions for primary drying which use low shelf
temperature and a moderate vacuum, desorption drying is facilitated by
raising shelf temperature(50 to 60°C) and reducing chamber pressure to a
minimum.
20. • Care should be exercised in raising shelf temperature too
highly; since, protein polymerization or biodegradation may
result from using high processing temperature during
secondary drying.
• Secondary drying is usually carried out for about 10-20 hours,
whereas primary drying is carried out for 2hours.
21. PACKING
• After drying the vacuum is
replaced by filtered dry air or
nitrogen to establish atmospheric
pressure
• Ampoules are sealed by either tip
sealing or pull sealing method
• Vials and bottles are sealed with
rubber closures and aluminum
caps
22. ADVANTAGES OF FREEZE DRYING OVER
CONVENTIONAL DRYING
Product quality Freeze drying Conventional drying
Form of wet material
to be dried
Whole, liquids
Pieces, powders
Pieces
Dry shape and form Maintained Shriveled
Appearance Nearly same Shriveled
color Maintained Faded
Rehydration Fast Slow
Heat exposure 0-150oC 200-300oC
Oxygen exposure Very low High
Retained volatiles Excellent Poor
23. SOME LYOPHILIZED FORMULATIONS
Drug Category Route Of
Administration
Marketed Name
Amphotericin B &
Cholestryl sulphate
Anti-fungal IV Infusion at 2-4
mg/kg/hr
Amphotec®
(Sequus
pharmaceuticals)
Chlorthiazide
sodium
Diuretic & anti-
hypertensive
IV Infusion , IV
bolus
Diuril®
(Merck)
Cisplastin Anti-neoplastic IV Infusion,
Platinol®
(Bristol Myers
Oncolgy)
Gemcitabine Anti-neoplastic IV Infusion over 30
min
Genzer®
(Lilly)
Thiopental sodium Short acting
anesthetic IV Infusion
Pentothal sodium®
(Baxter)
24. ADVANTAGES
Thermo labile materials can be dried
Loss of volatile materials is less.
Moisture level can be kept as low as possible
Sterility can be maintained
Final product can be stored in ambient temperature, if well
sealed with inert atmosphere
25. DISADVANTAGES
Equipment & running costs are high
Increased handling and processing time.
Need for sterile diluents upon reconstitution.
It is difficult to adopt the method for solutions containing non
aqueous solvents
Product is prone to oxidation so it should be packed in vacuum
26. APPLICATIONS
od and make it very
n the forms of freeze-
• PHARMACEUTICAL
1. Pharmaceutical companies often use freeze-drying to
increase the shelf life of products, such as vaccines and
other injectables.
2. By removing the water from the material and sealing the
material in a vial, the material can be easily stored,
shipped, and later reconstituted to its original form for
injection.
• FOOD INDUSTRY
1. Freeze-drying is used to preserve fo
lightweight.
2. The process has been popularized i
dried ice cream.
27. CONCLUSION
A freeze dried product with the best attributes andquality.
In freeze drying, minimal structural changes or shrinkage.
In freeze drying process, nutrients are largelyretained.
Freeze drying system includes vacuum and refrigeration equipments. The
initial costs are relatively high up to 4 times than conventional drying.
28. REFERENCES
1. Lachman L ,The theory & practice of IndustrialPharmacy,
Varghese publication,Bombay,Pg no: 762.
2. Subramanyam CVS , Pharmaceutical
Engineering,Published by Vallabh Prakashan,
Pg no: 307
3. Remington, The Science & Practice of Pharmacy,21st
edition,vol 2,pg no. 959.
31. Define the following terms:
[Lyophilization, etc]
Respond to the following questions:
Give a detailed account of ………………
Explain in details the process of …………..
Describe in details with examples the…………
With examples, illustrate the pharmaceutical applications of ……………
32. Group work discussional questions:
Explain in details the process of………
Describe with examples in details the…………..
With examples, illustrate the pharmaceutical applications of…….